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Advances in Neurotrauma
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Advances in Neurotrauma

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 36707

Special Issue Editor

Prof. Dr. Guoyi Gao

E-Mail Website
Guest Editor
Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China
Interests: traumatic brain injury; spinal cord injury; biomarker; treatment; mechanism exploration; clinical study
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Traumatic brain injury spinal cord injury remains the significant challenge to the healthcare and policy making. The further improvement of the clinical management depends on the efforts from lab findings and transformation practice. Neurotrauma includes a group of diseases, and every disease has its heterogeneity in terms of the causes, the pathophysiological process and clinical scenarios. To lower the risk of mortality and benefit the living quality of survivors remains the targets of neurotrauma study globally.

In recent years, with the continuous effort from all continents, the progress of basic research and clinical study achieved numerous progress. The most plausible achievement is the promotion of neurotrauma management in LIMIC areas, attributed to the widely implementation of advanced theories and techniques. The research in neurotrauma covers a big field of neuroscience study, including a broad range of topics related to both the clinical and laboratory investigation of traumatic brain and spinal cord injury.

The special issue welcomes manuscripts on the basic pathobiology of injury to the central nervous system, while considering preclinical and clinical trials targeted at improving both the early management and long-term care and recovery of traumatically injured patients.

Prof. Dr. Guoyi Gao
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Traumatic brain injury
  • Spinal cord injury
  • Biomarker
  • Treatment
  • Mechanism exploration
  • Clinical study

Published Papers (19 papers)

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9 pages, 590 KiB  
Article
Association between Traumatic Subarachnoid Hemorrhage and Acute Respiratory Failure in Moderate-to-Severe Traumatic Brain Injury Patients
by Min Li, Rui Wang, Qi-Xing Fang, Yi-Xuan He, Ying-Wu Shi, Shun-Nan Ge, Rui-Na Ma and Yan Qu
J. Clin. Med. 2022, 11(14), 3995; https://doi.org/10.3390/jcm11143995 - 10 Jul 2022
Viewed by 1653
Abstract
Acute respiratory failure (ARF) with a high incidence among moderate-to-severe traumatic brain injury (M-STBI) patients plays a pivotal role in worsening neurological outcomes. Traumatic subarachnoid hemorrhage (tSAH) is highly prevalent in M-STBI, which is associated with significant adverse outcomes. In this retrospective cohort [...] Read more.
Acute respiratory failure (ARF) with a high incidence among moderate-to-severe traumatic brain injury (M-STBI) patients plays a pivotal role in worsening neurological outcomes. Traumatic subarachnoid hemorrhage (tSAH) is highly prevalent in M-STBI, which is associated with significant adverse outcomes. In this retrospective cohort study, we aimed to explore the association between the severity of the tSAH and ARF in the M-STBI population. A total of 771 subjects were reviewed. Clinical and neuroimaging data of M-STBI patients were retrospectively collected, and ARF was ascertained retrospectively based on their electronic medical record. The degree of tSAH was classified according to Fisher’s criteria, and the grade of tSAH was dichotomized to a low Fisher grade (Fisher grade 1–2) and a high Fisher grade (Fisher grade 3–4). After exclusion procedures, the data of 695 M-STBI patients were analyzed. A total of 284 (30.8%) had a high Fisher grade on admission. The overall rate of ARF within 48 h upon admission was 34.4% (239/695); it was 29.5% (142/481) and 46.3% (99/214) for the low and high Fisher groups, respectively. In a full cohort, a high Fisher grade was associated with ARF after adjusting for age, gender, GCS, smoking history, comorbidities, multiple injuries, characteristics of TBI, and pulmonary factors (OR 1.78; 95% CI, 1.11–2.85, p = 0.016). This result remained robust in the comparisons after PSM (71/132, 42.8% vs. 53/132, 31.9%; OR, 1.59; 95% CI, 1.02–2.49, p = 0.042). A high Fisher SAH grade exposure on admission is associated with ARF in M-STBI patients. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 2157 KiB  
Article
Prediction of Intracranial Infection in Patients under External Ventricular Drainage and Neurological Intensive Care: A Multicenter Retrospective Cohort Study
by Pengfei Fu, Yi Zhang, Jun Zhang, Jin Hu and Yirui Sun
J. Clin. Med. 2022, 11(14), 3973; https://doi.org/10.3390/jcm11143973 - 08 Jul 2022
Cited by 2 | Viewed by 1591
Abstract
Objective: To generate an optimal prediction model along with identifying major contributors to intracranial infection among patients under external ventricular drainage and neurological intensive care. Methods: A retrospective cohort study was conducted among patients admitted into neurointensive care units between 1 [...] Read more.
Objective: To generate an optimal prediction model along with identifying major contributors to intracranial infection among patients under external ventricular drainage and neurological intensive care. Methods: A retrospective cohort study was conducted among patients admitted into neurointensive care units between 1 January 2015 and 31 December 2020 who underwent external ventricular drainage due to traumatic brain injury, hydrocephalus, and nonaneurysmal spontaneous intracranial hemorrhage. Multivariate logistic regression in combination with the least absolute shrinkage and selection operator regression was applied to derive prediction models and optimize variable selections. Other machine-learning algorithms, including the support vector machine and K-nearest neighbor, were also applied to derive alternative prediction models. Five-fold cross-validation was used to train and validate each model. Model performance was assessed by calibration plots, receiver operating characteristic curves, and decision curves. A nomogram analysis was developed to explicate the weights of selected features for the optimal model. Results: Multivariate logistic regression showed the best performance among the three tested models with an area under curve of 0.846 ± 0.006. Six variables, including hemoglobin, albumin, length of operation time, American Society of Anesthesiologists grades, presence of traumatic subarachnoid hemorrhage, and a history of diabetes, were selected from 37 variable candidates as the top-weighted prediction features. The decision curve analysis showed that the nomogram could be applied clinically when the risk threshold is between 20% and 100%. Conclusions: The occurrence of external ventricular-drainage-associated intracranial infections could be predicted using optimal models and feature-selection approaches, which would be helpful for the prevention and treatment of this complication in neurointensive care units. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 1438 KiB  
Article
DJ-1 Alleviates Neuroinflammation and the Related Blood-Spinal Cord Barrier Destruction by Suppressing NLRP3 Inflammasome Activation via SOCS1/Rac1/ROS Pathway in a Rat Model of Traumatic Spinal Cord Injury
by Lingxin Cai, Liansheng Gao, Guoqiang Zhang, Hanhai Zeng, Xinyan Wu, Xiaoxiao Tan, Cong Qian and Gao Chen
J. Clin. Med. 2022, 11(13), 3716; https://doi.org/10.3390/jcm11133716 - 27 Jun 2022
Cited by 7 | Viewed by 1915
Abstract
DJ-1 has been shown to play essential roles in neuronal protection and anti-inflammation in nervous system diseases. This study aimed to explore how DJ-1 regulates neuroinflammation after traumatic spinal cord injury (t-SCI). The rat model of spinal cord injury was established by the [...] Read more.
DJ-1 has been shown to play essential roles in neuronal protection and anti-inflammation in nervous system diseases. This study aimed to explore how DJ-1 regulates neuroinflammation after traumatic spinal cord injury (t-SCI). The rat model of spinal cord injury was established by the clamping method. The Basso, Beattie, Bresnahan (BBB) score and the inclined plane test (IPT) were used to evaluate neurological function. Western blot was then applied to test the levels of DJ-1, NLRP3, SOCS1, and related proinflammatory factors (cleaved caspase 1, IL-1β and IL-18); ROS level was also examined. The distribution of DJ-1 was assessed by immunofluorescence staining (IF). BSCB integrity was assessed by the level of MMP-9 and tight junction proteins (Claudin-5, Occludin and ZO-1). We found that DJ-1 became significantly elevated after t-SCI and was mainly located in neurons. Knockdown of DJ-1 with specific siRNA aggravated NLRP3 inflammasome-related neuroinflammation and strengthened the disruption of BSCB integrity. However, the upregulation of DJ-1 by Sodium benzoate (SB) reversed these effects and improved neurological function. Furthermore, SOCS1-siRNA attenuated the neuroprotective effects of DJ-1 and increased the ROS, Rac1 and NLRP3. In conclusion, DJ-1 may alleviate neuroinflammation and the related BSCB destruction after t-SCI by suppressing NLRP3 inflammasome activation by SOCS1/Rac1/ROS pathways. DJ-1 shows potential as a feasible target for mediating neuroinflammation after t-SCI. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 1439 KiB  
Article
The Prognostic Value of Deleted in Colorectal Cancer (DCC) Receptor and Serum Netrin-1 in Severe Traumatic Brain Injury
by Yuanda Zhang, Qiao Zhang, Lihua Sun, Dongxu Zhao, Cijie Ruan, Jue Zhou, Haoyuan Tan and Yinghui Bao
J. Clin. Med. 2022, 11(13), 3700; https://doi.org/10.3390/jcm11133700 - 27 Jun 2022
Viewed by 1581
Abstract
Traumatic brain injury (TBI) is a common neurological disease. Netrin-1 and deleted in colorectal cancer (DCC) receptor are potential biomarkers associated with nerve regeneration and immune regulation. We aimed to investigate the ability of the DCC receptor and Netrin-1 to predict a high [...] Read more.
Traumatic brain injury (TBI) is a common neurological disease. Netrin-1 and deleted in colorectal cancer (DCC) receptor are potential biomarkers associated with nerve regeneration and immune regulation. We aimed to investigate the ability of the DCC receptor and Netrin-1 to predict a high ICP level after operation in severe traumatic brain injury and their prognostic significance. This study is a prospective observational study. We selected 23 patients with traumatic brain injury who had undergone surgical operations as subjects. Immunohistochemical staining was performed on the contusion tissue that was removed by the operation to determine the expression of DCC receptor. At the same time, enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum Netrin-1 content. Determination of intracranial pressure (ICP) value was measured by intraventricular catheter. The Glasgow Outcome Scale (GOS) score at six months after trauma was defined as the main study endpoint. The results showed that serum Netrin-1 concentrations of patients in the critical TBI group (GCS 3–5 points) was significantly lower than that in the severe TBI group (GCS 6–8 points). The ICP peak and average mannitol consumption in the high Netrin-1 group were significantly lower than those in the low Netrin-1 group. DCC receptor-positive patients had a significantly lower ICP peak. There was no significant difference in six month-GOS scores between patients in the high and low Netrin-1 groups, while DCC receptor concentrations below 3.82 ng/mL predicted poor prognosis (GOS 1–3 points). In conclusion, the expression level of the DCC receptor can better evaluate the postoperative high ICP level and prognosis than the level of serum Netrin-1 in severe traumatic brain injury. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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18 pages, 4937 KiB  
Article
Comprehensive RNA Expression Analysis Revealed Biological Functions of Key Gene Sets and Identified Disease-Associated Cell Types Involved in Rat Traumatic Brain Injury
by Qilin Tang, Mengmeng Song, Rongrong Zhao, Xiao Han, Lin Deng, Hao Xue, Weiguo Li and Gang Li
J. Clin. Med. 2022, 11(12), 3437; https://doi.org/10.3390/jcm11123437 - 15 Jun 2022
Cited by 1 | Viewed by 1820
Abstract
Traumatic brain injury (TBI) is a worldwide public health concern without major therapeutic breakthroughs over the past decades. Developing effective treatment options and improving the prognosis of TBI depends on a better understanding of the mechanisms underlying TBI. This study performed a comprehensive [...] Read more.
Traumatic brain injury (TBI) is a worldwide public health concern without major therapeutic breakthroughs over the past decades. Developing effective treatment options and improving the prognosis of TBI depends on a better understanding of the mechanisms underlying TBI. This study performed a comprehensive analysis of 15 RNA expression datasets of rat TBIs from the GEO database. By integrating the results from the various analyses, this study investigated the biological processes, pathways, and cell types associated with TBI and explored the activity of these cells during various TBI phases. The results showed the response to cytokine, inflammatory response, bacteria-associated response, metabolic and biosynthetic processes, and pathways of neurodegeneration to be involved in the pathogenesis of TBI. The cellular abundance of microglia, perivascular macrophages (PM), and neurons were found to differ after TBI and at different times postinjury. In conclusion, immune- and inflammation-related pathways, as well as pathways of neurodegeneration, are closely related to TBI. Microglia, PM, and neurons are thought to play roles in TBI with different activities that vary by phase of TBI. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 3477 KiB  
Article
Decreased Expression of CIRP Induced by Therapeutic Hypothermia Correlates with Reduced Early Brain Injury after Subarachnoid Hemorrhage
by Haibin Dai, Yan Zhou, Yue Lu, Xiangsheng Zhang, Zong Zhuang, Yongyue Gao, Guangjie Liu, Chunlei Chen, Jin Ma, Wei Li and Chunhua Hang
J. Clin. Med. 2022, 11(12), 3411; https://doi.org/10.3390/jcm11123411 - 14 Jun 2022
Cited by 2 | Viewed by 1460
Abstract
Early brain injury is considered to be a primary reason for the poor prognosis of patients suffering from subarachnoid hemorrhage (SAH). Due to its pro-inflammatory activity, cold-inducible RNA-binding protein (CIRP) has been implicated in the ischemic brain insult, but its possible interplay with [...] Read more.
Early brain injury is considered to be a primary reason for the poor prognosis of patients suffering from subarachnoid hemorrhage (SAH). Due to its pro-inflammatory activity, cold-inducible RNA-binding protein (CIRP) has been implicated in the ischemic brain insult, but its possible interplay with hypothermia in SAH treatment remains to be evaluated. One-hundred and thirty-eight Sprague-Dawley rats (300–350 g males) were randomly allocated into the following groups: sham-operated (Sham); SAH; and SAH + hypothermia (SAH + H), each comprised of 46 animals. After treatments, the brain tissues of the three groups were randomly collected after 12 h, 1 d, 3 d, and 7 d, and the expression levels of the CIRP and mitochondrial apoptosis pathway-related proteins Bax, Bcl-2, caspase-9, caspase-3, and cytochrome c measured using Western blotting and real-time PCR. Brain damage was assessed by TUNEL and Nissl staining, the electron microscopy of brain tissue slices as well as functional rotarod tests. Expression of CIRP, Bax, caspase-9, caspase-3, and cytochrome c as well as reduced motor function incidence were higher in the SAH group, particularly during the first 3 d after SAH induction. Hypothermia blunted these SAH responses and apoptosis, thereby indicating reduced inflammatory signaling and less brain cell injury in the early period after SAH. Hypothermia treatment was found to effectively protect the brain tissue from early SAH injury in a rat model and its further evaluation as a therapeutic modality in SAH patients requires further study. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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9 pages, 1686 KiB  
Article
Levels of lncRNA GAS5 in Plasma of Patients with Severe Traumatic Brain Injury: Correlation with Systemic Inflammation and Early Outcome
by Jin Lei, Xiao Zhang, Rui Tan, Yu Li, Kai Zhao and Hongquan Niu
J. Clin. Med. 2022, 11(12), 3319; https://doi.org/10.3390/jcm11123319 - 09 Jun 2022
Cited by 5 | Viewed by 1393
Abstract
Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding [...] Read more.
Scientific efforts continue to concentrate on elucidating the complex molecular mechanisms underlying traumatic brain injury (TBI), and recent reports suggest that epigenetic regulation including long non-coding RNA (lncRNA) is involved. The present study aimed to investigate the plasma concentration of a long non-coding RNA, named growth arrest-specific 5 (GAS5), in a group of 45 patients with severe TBI (sTBI), and to analyze the correlations of GAS5 with TBI onset, injury severity, systemic inflammation, and early outcome of the patients. It was found that plasma GAS5 levels were substantially increased in sTBI patients compared with the relative controls (p < 0.001). Further, significantly higher expression of plasma GAS5 was observed in patients with a Glasgow Coma Scale (GCS) score of less than five (p = 0.002) or unfavorable outcome at discharge (p < 0.001). Circulating GAS5 expression had a negative correlation with GCS score (r = −0.406, p = 0.006), and positive correlations with white blood cell count (r = 0.473, p = 0.001), neutrophil count (r = 0.502, p < 0.001), and neutrophil/lymphocyte ratio (NLR) (r = 0.398, p = 0.007). Univariate and multivariate logistic regression analyses revealed that GCS score (OR = 0.318, 95% CI 0.132–0.767, p = 0.011) and GAS5 (OR = 2.771, 95% CI 1.025–7.494, p = 0.045) were the two independent predictors for early outcome of patients. The receiver operating characteristic (ROC) curves showed good prognostic values of GCS score (AUC = 0.856, 95% CI: 0.719–0.943) and GAS5 expression (AUC = 0.798, 95% CI: 0.651–0.903). Importantly, the combined use of them can improve the prognostic ability of TBI with an AUC of 0.895 (95% CI: 0.767–0.966). Collectively, our study indicated that the levels of lncRNA GAS5 in circulation were elevated following severe TBI and correlated well with injury severity and inflammatory parameters. In addition, GAS5 as well as GCS scores may have the potential to predict the early outcome of TBI patients. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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11 pages, 5460 KiB  
Article
Brain Tissue Damage Induced by Multimodal Neuromonitoring In Situ during MRI after Severe Traumatic Brain Injury: Incidence and Clinical Relevance
by Daniel Pinggera, Paul Rhomberg, Ronny Beer, Claudius Thomé and Ondra Petr
J. Clin. Med. 2022, 11(11), 3169; https://doi.org/10.3390/jcm11113169 - 02 Jun 2022
Cited by 1 | Viewed by 1337
Abstract
Both neuromonitoring and early magnetic resonance imaging (MRI) provide crucial information for treatment management and prognosis in patients with severe traumatic brain injury (sTBI). So far, neuromonitoring in situ impedes the routine implementation of MRI due to safety concerns. We aimed to evaluate [...] Read more.
Both neuromonitoring and early magnetic resonance imaging (MRI) provide crucial information for treatment management and prognosis in patients with severe traumatic brain injury (sTBI). So far, neuromonitoring in situ impedes the routine implementation of MRI due to safety concerns. We aimed to evaluate the brain tissue damage induced by inserted neuromonitoring devices and its clinical relevance. Nineteen patients with sTBI and being exposed to at least one MRI with neuromonitoring in situ and one follow-up MRI after neuromonitoring removal were analyzed. All MRIs were reviewed for specific tissue damage. Three females and sixteen males (aged 20–74 years, mean 42.8 years) with an initial median GCS of 5 (range 3–8) were analyzed. No lesion was observed in six patients (31.6%), whereas another six patients (31.6%) demonstrated a detectable probe trajectory. Probe-related tissue damage was visible in seven patients (36.8%) with the size of the lesion prone to further enlarge with increasing cumulative duration of MRI examinations. Upon interdisciplinary evaluation, the lesions were not considered clinically relevant. Neuromonitoring probes in situ during MRI examinations may cause local brain tissue damage, yet without any clinical implications if placed correctly. Therefore, indications must be strictly based on joint decision from all involved disciplines. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 3487 KiB  
Article
Brain Extract of Subacute Traumatic Brain Injury Promotes the Neuronal Differentiation of Human Neural Stem Cells via Autophagy
by Zhenghui He, Lijian Lang, Jiyuan Hui, Yuxiao Ma, Chun Yang, Weiji Weng, Jialin Huang, Xiongfei Zhao, Xiaoqi Zhang, Qian Liang, Jiyao Jiang and Junfeng Feng
J. Clin. Med. 2022, 11(10), 2709; https://doi.org/10.3390/jcm11102709 - 11 May 2022
Cited by 2 | Viewed by 1960
Abstract
Background: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for [...] Read more.
Background: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. Methods: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. Results: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. Conclusions: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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19 pages, 8588 KiB  
Article
Activation of Sigma-1 Receptor Alleviates ER-Associated Cell Death and Microglia Activation in Traumatically Injured Mice
by Mingming Shi, Liang Liu, Xiaobin Min, Liang Mi, Yan Chai, Fanglian Chen, Jianhao Wang, Shuyuan Yue, Jianning Zhang, Quanjun Deng and Xin Chen
J. Clin. Med. 2022, 11(9), 2348; https://doi.org/10.3390/jcm11092348 - 22 Apr 2022
Cited by 10 | Viewed by 2376
Abstract
Background: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is associated with neuroinflammation and subsequent cell death following traumatic brain injury (TBI). The sigma-1 receptor (Sig-1R) acts as a dynamic pluripotent modulator of fundamental cellular processes at the mitochondria-associated membranes (MAMs). The [...] Read more.
Background: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is associated with neuroinflammation and subsequent cell death following traumatic brain injury (TBI). The sigma-1 receptor (Sig-1R) acts as a dynamic pluripotent modulator of fundamental cellular processes at the mitochondria-associated membranes (MAMs). The activation of Sig-1R is neuroprotective in a variety of central nervous system diseases, but its impact on ER stress induced by traumatic brain injury is not known. This study investigated the role of Sig-1R in regulating the ER stress-mediated microglial activation and programmed cell death (apoptosis and pyroptosis) induced by TBI. Methods: Ten human brain tissues were obtained from The Tianjin Medical University General Hospital. Four normal brain tissues were obtained from patients who underwent surgery for cerebral vascular malformation, through which peripheral brain tissues were isolated. Six severe TBI tissues were from patients with brain injury caused by accidents. None of the patients had any other known neurological disorders. Mice with Sig-1R deletion using CRISPR technology were subjected to controlled cortical impact-induced injury. In parallel, wild type C57BL/6J mice were analyzed for outcomes after they were exposed to TBI and received the Sig-1R agonist PRE-084 (10 mg/kg daily for three days) either alone or in combination with the Sig-1R antagonist BD-1047 (10 mg/kg). Results: The expression of Sig-1R and the 78 kDa glucose-regulated protein, a known UPR marker, were significantly elevated in the injured cerebral tissues from TBI patients and mice subjected to TBI. PRE-084 improved neurological function, restored the cerebral cortical perfusion, and ameliorated and brain edema in C57BL/6J mice subjected to TBI by reducing endoplasmic reticulum stress-mediated apoptosis, pyroptosis, and microglia activation. The effect of PRE-084 was abolished in mice receiving Sig-1R antagonist BD-1047. Conclusions: ER stress and UPR were upregulated in TBI patients and mice subjected to TBI. Sig-1R activation by the exogenous activator PRE-084 attenuated microglial cells activation, reduced ER stress-associated programmed cell death, and restored cerebrovascular and neurological function in TBI mice. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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11 pages, 1885 KiB  
Article
Cerebral Pulsatility Index and In-Hospital Mortality in Chinese Patients with Traumatic Brain Injury: A Retrospective Cohort Study
by Tao Mei, Quan Zhou, Lie Chen, Zheyong Jia, Wei Xiao and Lixin Xu
J. Clin. Med. 2022, 11(6), 1559; https://doi.org/10.3390/jcm11061559 - 12 Mar 2022
Viewed by 1501
Abstract
There are limited studies on the relationship between the vascular transcranial Doppler (TCD) pulsatility index (PI) and in-hospital mortality in patients with traumatic brain injury (TBI). To address this issue, we conducted this study to explore whether, in newly diagnosed Chinese TBI patients, [...] Read more.
There are limited studies on the relationship between the vascular transcranial Doppler (TCD) pulsatility index (PI) and in-hospital mortality in patients with traumatic brain injury (TBI). To address this issue, we conducted this study to explore whether, in newly diagnosed Chinese TBI patients, the PI is an independent predictor of the in-hospital mortality rate after adjusting for other covariates. This study is a retrospective cohort study. From 24 March 2019 to 24 January 2020, we recruited 144 Chinese patients with newly diagnosed TBI from a Chinese hospital. The independent variable was the PI, and the dependent variable was in-hospital mortality in TBI patients. The relationship between the PI and in-hospital mortality in TBI patients was nonlinear and had an inflection point of 1.11. In the multivariate analysis, after adjusting for potential confounders, the effect sizes and confidence intervals per additional 0.1 units on the left and right sides of the inflection point were 4.09 (1.30–12.83) and 1.42 (0.93–2.17). The relationship between the PI and in-hospital mortality was nonlinear. The PI was positively related with in-hospital mortality when the PI was less than 1.11. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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8 pages, 14754 KiB  
Article
Minimally Invasive Surgery in Chronic Subdural Hematoma: Prognosis and Recurrence Factors of 516 Cases in a Single Center
by Min Xu, Weiguo Tan, Wenhua Wang, Dongdong Wang, Wei Zeng and Cunzu Wang
J. Clin. Med. 2022, 11(5), 1321; https://doi.org/10.3390/jcm11051321 - 28 Feb 2022
Cited by 2 | Viewed by 1789
Abstract
Objective: To investigate the effects of minimally invasive surgery (MIS) using a novel YL-1 puncture needle and summarize the risk factors of recurrence in chronic subdural hematoma (CSDH). Methods: We performed a retrospective analysis in 516 hospitalized patients with CSDH from January 2013 [...] Read more.
Objective: To investigate the effects of minimally invasive surgery (MIS) using a novel YL-1 puncture needle and summarize the risk factors of recurrence in chronic subdural hematoma (CSDH). Methods: We performed a retrospective analysis in 516 hospitalized patients with CSDH from January 2013 to December 2018 in Northern Jiangsu People’s Hospital. Patients’ gender, age, history of trauma, use of anticoagulants, history of disturbed liver or renal function, history of heart disease, history of malignant tumor, history of diabetes, hemodialysis, coagulopathy, alcoholism, imaging indicators, and postoperative application of urokinase or atorvastatin were recorded. Recurrence is defined by imaging examination with or without clinical presentation three months after discharge. Results: In total, 483 patients (93.60%) benefited from MIS by YL-1 needle. Gender, age, history of head trauma, history of disturbed liver function, history of heart disease, history of malignant tumor, history of diabetes, history of hemodialysis, coagulopathy, alcoholism, hematoma location, hematoma densities, septum formation, maximum thickness, encephalatrophy, and use of atorvastatin and urokinase were shown to be non-significantly associated with postoperative recurrence (p > 0.05). The use of anticoagulants was significantly associated with postoperative recurrence (p > 0. 05). Logistic analysis showed that the use of anticoagulants is an independent factor predicting postoperative recurrence (p > 0. 05). Conclusions: The novel YL-1 puncture needle turned out to be a safe and effective minimally invasive surgery, and the use of anticoagulants is an independent risk factor predicting postoperative recurrence in CSDH, which can provide MIS and early therapeutic strategies for neurosurgeons. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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13 pages, 1953 KiB  
Article
Chinese Admission Warning Strategy for Predicting the Hospital Discharge Outcome in Patients with Traumatic Brain Injury
by Ruizhe Zheng, Zhongwei Zhuang, Changyi Zhao, Zhijie Zhao, Xitao Yang, Yue Zhou, Shuming Pan, Kui Chen, Keqin Li, Qiong Huang, Yang Wang and Yanbin Ma
J. Clin. Med. 2022, 11(4), 974; https://doi.org/10.3390/jcm11040974 - 13 Feb 2022
Cited by 3 | Viewed by 1614
Abstract
Objective: To develop and validate an admission warning strategy that incorporates the general emergency department indicators for predicting the hospital discharge outcome of patients with traumatic brain injury (TBI) in China. Methods: This admission warning strategy was developed in a primary cohort that [...] Read more.
Objective: To develop and validate an admission warning strategy that incorporates the general emergency department indicators for predicting the hospital discharge outcome of patients with traumatic brain injury (TBI) in China. Methods: This admission warning strategy was developed in a primary cohort that consisted of 605 patients with TBI who were admitted within 6 h of injury. The least absolute shrinkage and selection operator and multivariable logistic regression analysis were used to develop the early warning strategy of selected indicators. Two sub-cohorts consisting of 180 and 107 patients with TBI were used for the external validation. Results: Indicators of the strategy included three categories: baseline characteristics, imaging and laboratory indicators. This strategy displayed good calibration and good discrimination. A high C-index was reached in the internal validation. The multicenter external validation cohort still showed good discrimination C-indices. Decision curve analysis (DCA) showed the actual needs of this strategy when the possibility threshold was 0.01 for the primary cohort, and at thresholds of 0.02–0.83 and 0.01–0.88 for the two sub-cohorts, respectively. In addition, this strategy exhibited a significant prognostic capacity compared to the traditional single predictors, and this optimization was also observed in two external validation cohorts. Conclusions: We developed and validated an admission warning strategy that can be quickly deployed in the emergency department. This strategy can be used as an ideal tool for predicting hospital discharge outcomes and providing objective evidence for early informed consent of the hospital discharge outcome to the family members of TBI patients. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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8 pages, 246 KiB  
Article
Serum Levels of MMP-8 and MMP-9 as Markers in Chronic Subdural Hematoma
by Gao-Jian Su, Jie Gao, Chu-Wei Wu, Jun-Feng Zou, Di Zhang, Dong-Liang Zhu, Jun Liu, Jie-Hua Zhang and Xian-Jian Huang
J. Clin. Med. 2022, 11(4), 902; https://doi.org/10.3390/jcm11040902 - 09 Feb 2022
Cited by 5 | Viewed by 1367
Abstract
Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed [...] Read more.
Chronic subdural hematoma (CSDH) is a common neurological disease that involves the collection of blood products in the subdural space. The progression of CSDH is an angiogenic and inflammatory process, but the multifactorial mechanisms underlying CSDH are still not fully understood. We aimed to identify one or more factors that may play an important role in the development of CSDH. We enrolled 83 patients with CSDH, including 17 postoperative patients, and analyzed 20 markers in the hematoma fluid and peripheral blood of each patient. Overall differential gene expression was examined to identify the representative markers. The concentration of MMP-8 was significantly lower in the postoperative group than in the preoperative group. The concentration of MMP-9 was significantly higher in the postoperative group than in the preoperative group. These findings indicate that MMP-8 and MMP-9 may play important roles in the pathophysiology of CSDH. Understanding the pathways associated with CSDH may provide insights for improving disease outcomes. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
9 pages, 720 KiB  
Article
Clinical Significance of Multiparameter Intracranial Pressure Monitoring in the Prognosis Prediction of Hypertensive Intracerebral Hemorrhage
by Yongbo Yang, Yuchun Pan, Chunlei Chen, Penglai Zhao and Chunhua Hang
J. Clin. Med. 2022, 11(3), 671; https://doi.org/10.3390/jcm11030671 - 28 Jan 2022
Cited by 5 | Viewed by 1879
Abstract
Objective: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). Methods: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients [...] Read more.
Objective: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). Methods: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients underwent removal of intracranial hemorrhage and decompressive craniectomy after admission. A ventricular ICP monitoring probe was used to continuously and invasively monitor mean arterial pressure (MAP) and ICP after surgery. The NEUMATIC system was used to collect ICP data, including pressure reactivity index (PRx), ICP dose (DICP), amplitude and pressure regression (RAP), and cerebral perfusion pressure (CPP). The mean PRx, CPP, RAP, ICP, and DICP20 mmHg × h were calculated with 1 h as the time segment. According to the Glasgow outcome scale (GOS) scores after discharge, the patients were grouped into the poor prognosis group (GOS I–III) and the good prognosis group (GOS IV and V). The two groups were compared in terms of GOS scores in the treatment and prediction of prognosis of patients. Results: The good prognosis group showed significantly lower values of mean ICP, DICP20 mmHg × h, RAP, and PRx than the poor prognosis group, while CPP was significantly higher (p < 0.001). Conclusions: PRx, DICP, RAP, and CPP could reflect intracranial changes in patients and were significantly correlated with the prognosis of the patients. Mean ICP, PRx, DICP20 mmHg × h, and RAP were negatively correlated with prognosis, while CPP was positively correlated with prognosis. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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15 pages, 4421 KiB  
Article
Downregulation of the LncRNA MEG3 Promotes Osteogenic Differentiation of BMSCs and Bone Repairing by Activating Wnt/β-Catenin Signaling Pathway
by Juan Liu, Xin Qi, Xiao-Hong Wang, Hong-Sheng Miao, Zi-Chao Xue, Le-Le Zhang, San-Hu Zhao, Liang-Hao Wu, Guo-Yi Gao, Mei-Qing Lou and Cheng-Qing Yi
J. Clin. Med. 2022, 11(2), 395; https://doi.org/10.3390/jcm11020395 - 13 Jan 2022
Cited by 7 | Viewed by 2106
Abstract
Background: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells [...] Read more.
Background: Previous studies have demonstrated that long non-coding RNA maternally expressed gene 3 (MEG3) emerged as a key regulator in development and tumorigenesis. This study aims to investigate the function and mechanism of MEG3 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explores the use of MEG3 in skull defects bone repairing. Methods: Endogenous expression of MEG3 during BMSCs osteogenic differentiation was detected by quantitative real-time polymerase chain reaction (qPCR). MEG3 was knockdown in BMSCs by lentiviral transduction. The proliferation, osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs were assessed by Cell Counting Kit-8 (CCK-8) assay, qPCR, alizarin red and alkaline phosphatase staining. Western blot was used to detect β-catenin expression in MEG3 knockdown BMSCs. Dickkopf 1 (DKK1) was used to block wnt/β-catenin pathway. The osteogenic-related genes and proteins expression of MEG3 knockdown BMSCs after wnt/β-catenin inhibition were assessed by qPCR, alizarin red and alkaline phosphatase staining. MEG3 knockdown BMSCs scaffold with PHMG were implanted in a critical-sized skull defects of rat model. Micro-computed tomography(micro-CT), hematoxylin and eosin staining and immunohistochemistry were performed to evaluate the bone repairing. Results: Endogenous expression of MEG3 was increased during osteogenic differentiation of BMSCs. Downregulation of MEG3 could promote osteogenic differentiation of BMSCs in vitro. Notably, a further mechanism study revealed that MEG3 knockdown could activate Wnt/β-catenin signaling pathway in BMSCs. Wnt/β-catenin inhibition would impair MEG3-induced osteogenic differentiation of BMSCs. By using poly (3-hydroxybutyrate-co-3-hydroxyhexanoate, PHBHHx)-mesoporous bioactive glass (PHMG) scaffold with MEG3 knockdown BMSCs, we found that downregulation of MEG3 in BMSCs could accelerate bone repairing in a critical-sized skull defects rat model. Conclusions: Our study reveals the important role of MEG3 during osteogenic differentiation and bone regeneration. Thus, MEG3 engineered BMSCs may be effective potential therapeutic targets for skull defects. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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12 pages, 1110 KiB  
Article
Factors Associated with the Development of Coagulopathy after Open Traumatic Brain Injury
by Yuhui Chen, Jun Tian, Bin Chi, Shangming Zhang, Liangfeng Wei and Shousen Wang
J. Clin. Med. 2022, 11(1), 185; https://doi.org/10.3390/jcm11010185 - 30 Dec 2021
Cited by 10 | Viewed by 1734
Abstract
Background: The incidence of coagulopathy after open traumatic brain injury (TBI) is high. Coagulopathy can aggravate intracranial hemorrhage and further increase morbidity and mortality. The purpose of this study was to determine the clinical characteristics of coagulopathy after open TBI and its relationship [...] Read more.
Background: The incidence of coagulopathy after open traumatic brain injury (TBI) is high. Coagulopathy can aggravate intracranial hemorrhage and further increase morbidity and mortality. The purpose of this study was to determine the clinical characteristics of coagulopathy after open TBI and its relationship with the prognosis. Methods: This study retrospectively evaluated patients with isolated open TBI from December 2018 to December 2020. Coagulopathy was defined as international normalized ratio (INR) > 1.2, activated thromboplastin time (APTT) > 35 s, or platelet count <100,000/μL. We compared the relationship between the clinical, radiological, and laboratory parameters of patients with and without coagulopathy, and the outcome at discharge. Logistic regression analysis was used to evaluate the risk factors associated with coagulopathy. We then compared the effects of treatment with and without TXA in open TBI patients with coagulopathy. Results: A total of 132 patients were included in the study; 46 patients developed coagulopathy. Patients with coagulopathy had significantly lower platelet levels (170.5 × 109/L vs. 216.5 × 109/L, p < 0.001), and significantly higher INR (1.14 vs. 1.02, p < 0.001) and APTT (30.5 s vs. 24.5 s, p < 0.001) compared to those with no coagulopathy. A Low Glasgow Coma Scale (GCS) score, high neutrophil/lymphocyte ratio (NLR), low platelet/lymphocyte ratio (PLR), and hyperglycemia at admission were significantly associated with the occurrence of coagulopathy. Conclusions: Coagulopathy often occurs after open TBI. Patients with a low GCS score, high NLR, low PLR, and hyperglycemia at admission are at greater risk of coagulopathy, and therefore of poor prognosis. The efficacy of TXA in open TBI patients with coagulopathy is unclear. In addition, these findings demonstrate that PLR may be a novel indicator for predicting coagulopathy. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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Review

Jump to: Research

6 pages, 548 KiB  
Review
Lack of Objective Measurement in the Initial Screening and Follow-Up of Patients Who Report Whiplash Injury—Is Elastography of the Trapezius Muscle an Answer?
by Jure Aljinović, Blaž Barun, Benjamin Benzon, Ana Poljičanin and Tonko Vlak
J. Clin. Med. 2022, 11(13), 3851; https://doi.org/10.3390/jcm11133851 - 02 Jul 2022
Cited by 1 | Viewed by 1629
Abstract
Background: Painfully decreased cervical range of motion accompanied by muscle spasm is a common presentation of whiplash injury of the neck. Stiffness of the cervical muscles can be assessed by ultrasound shear wave elastography (SWE), expressed in kilopascals (kPa). The hypothesis: SWE of [...] Read more.
Background: Painfully decreased cervical range of motion accompanied by muscle spasm is a common presentation of whiplash injury of the neck. Stiffness of the cervical muscles can be assessed by ultrasound shear wave elastography (SWE), expressed in kilopascals (kPa). The hypothesis: SWE of the trapezius muscle is an objective measurement suitable for the initial screening and follow-up of patients who report whiplash injury. Methods and results: A total of 99 patients after whiplash injury were compared to 75 control participants. Mean trapezius stiffness was 82.24 ± 21.11 vs. 57.47 ± 13.82 for whiplash patients and controls, respectively. The cut-off value of SWE of 75.8 kPa showed 77% accuracy in correctly assigning patients to the whiplash or control group. To evaluate whether SWE can be used as a follow-up method of recovery after a whiplash injury, initial and endpoint SWE (after six months, n = 24) was carried out. Patients reporting no recovery showed similar SWE values as completely recovered patients. This finding refutes the second part of our hypothesis. Conclusions: SWE is a method that can be used for the initial screening of patients with whiplash injury, but we are still searching for an objective measurement that can be used in the follow-up of recovery. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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23 pages, 803 KiB  
Review
Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury
by Jing Wang, Junwen Wang, Xinyan Li and Kai Shu
J. Clin. Med. 2022, 11(11), 3223; https://doi.org/10.3390/jcm11113223 - 05 Jun 2022
Cited by 14 | Viewed by 4225
Abstract
Traumatic brain injury (TBI) is a complex, life-threatening condition that causes mortality and disability worldwide. No effective treatment has been clinically verified to date. Achieving effective drug delivery across the blood–brain barrier (BBB) presents a major challenge to therapeutic drug development for TBI. [...] Read more.
Traumatic brain injury (TBI) is a complex, life-threatening condition that causes mortality and disability worldwide. No effective treatment has been clinically verified to date. Achieving effective drug delivery across the blood–brain barrier (BBB) presents a major challenge to therapeutic drug development for TBI. Furthermore, the field of TBI biomarkers is rapidly developing to cope with the many aspects of TBI pathology and enhance clinical management of TBI. Exosomes (Exos) are endogenous extracellular vesicles (EVs) containing various biological materials, including lipids, proteins, microRNAs, and other nucleic acids. Compelling evidence exists that Exos, such as stem cell-derived Exos and even neuron or glial cell-derived Exos, are promising TBI treatment strategies because they pass through the BBB and have the potential to deliver molecules to target lesions. Meanwhile, Exos have decreased safety risks from intravenous injection or orthotopic transplantation of viable cells, such as microvascular occlusion or imbalanced growth of transplanted cells. These unique characteristics also create Exos contents, especially Exos-derived microRNAs, as appealing biomarkers in TBI. In this review, we explore the potential impact of cell-derived Exos and exosome-derived microRNAs on the diagnosis, therapy, and prognosis prediction of TBI. The associated challenges and opportunities are also discussed. Full article
(This article belongs to the Special Issue Advances in Neurotrauma)
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