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Brain Sciences
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Ischemic Brain Injury: Cerebral Metabolism and Imaging
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Ischemic Brain Injury: Cerebral Metabolism and Imaging

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuropharmacology and Neuropathology".

Deadline for manuscript submissions: closed (24 November 2023) | Viewed by 25120

Special Issue Editor

Dr. Wensheng Qu

E-Mail Website
Guest Editor
Department of Neurology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
Interests: stroke; energetic metabolism; neuroinflammation; cerebral blood flow; mitochondrial function

Special Issue Information

Dear Colleagues,

Ischemic brain injury, which is mainly attributed to a decrease in cerebral blood flow (CBF) into the brain, is dominantly known as acute ischemic stroke and also exists in other CNS diseases, such as small vessel disease, Alzheimer's disease and trauma. Energy supplement and cellular metabolism are under crisis after CBF depression, which contributes to changes such as cell necrocytosis, apoptosis, oxidative stress, inflammation, and glial scar formation.

Imaging techniques are valuable and necessary for monitoring these changes. These include laser Doppler blood flow monitoring, two-photo confocal imaging, color ultrasound imaging, laser speckle contrast imaging (LSI), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), imaging mass spectrometry (IMS), etc. Helped by the imaging, it is possible to measure ischemic changes such as CBF, microvasculature, and tissue/cellular metabolism in vitro and vivo.

This Special Issue is committed to publishing high-quality, independently peer-reviewed research. It stands at the interface between basic and clinical neurovascular research, and features relevant research highlighting cerebral vascular regulation, metabolism, and imaging after ischemic injuries that exist in associated CNS disorders. These publications are aimed at advancing the discovery of mechanisms, identifying new diagnostic imaging biomarkers, and finding potential therapeutic targets. 

Dr. Wensheng Qu
Guest Editor

Manuscript Submission Information

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Keywords

  • ischemic brain injury
  • vascular regulation
  • cerebral metabolism
  • imaging techniques

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Published Papers (9 papers)

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Research

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18 pages, 2342 KiB  
Article
Targeting Microglia/Macrophages Notch1 Protects Neurons from Pyroptosis in Ischemic Stroke
by Ran Chen, Hua Zhu, Zhihui Wang, Yonggang Zhang, Jin Wang, Yingao Huang, Lijuan Gu, Changyong Li, Xiaoxing Xiong and Zhihong Jian
Brain Sci. 2023, 13(12), 1657; https://doi.org/10.3390/brainsci13121657 - 29 Nov 2023
Cited by 5 | Viewed by 2518
Abstract
Background and Aims: The immune-inflammatory cascade and pyroptosis play an important role in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). The maintenance of immune homeostasis is inextricably linked to the Notch signaling pathway, but whether myeloid Notch1 affects microglia polarization as well as [...] Read more.
Background and Aims: The immune-inflammatory cascade and pyroptosis play an important role in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). The maintenance of immune homeostasis is inextricably linked to the Notch signaling pathway, but whether myeloid Notch1 affects microglia polarization as well as neuronal pyroptosis in CIRI is not fully understood. This study was designed to clarify the role of myeloid Notch1 in CIRI, providing new therapeutic strategies for ischemic stroke. Methods and Results: Myeloid-specific Notch1 knockout (Notch1M-KO) mice and the floxed Notch1 (Notch1FL/FL) mice were subjected to middle cerebral artery occlusion (MCAO). After 3 days of CIRI, we evaluated the neurological deficit score and cerebral infarction volume. Immunofluorescence staining was used to detect the expression of Notch1 and microglial subtype markers. Cerebral infiltrating macrophages were detected by flow cytometry. RT-qPCR was used to detect pro-inflammatory cytokines. Western blot was used to detect the expression of pyroptosis related proteins. The Notch1-siRNA transfected BV2 cells were co-cultured with HT22 cells to investigate the potential mechanisms by which microglial Notch1 affects neuronal pyroptosis induced by anoxia/reoxygenation in vitro. We found that Notch1 was activated in cerebral microglia/macrophages after CIRI. Myeloid Notch1 deficiency decreased the cerebral infarct volume (24.17 ± 3.29 vs. 36.17 ± 2.27, p < 0.001), neurological function scores (2.33 ± 0.47 vs. 3.17 ± 0.37, p < 0.001) and the infiltration of peripheral monocytes/macrophages (3.26 ± 0.53 vs. 5.67 ± 0.57, p < 0.01). Strikingly, myeloid-specific Notch1 knockout alleviated pyroptosis. Compared with microglia M1, increased microglia M2 were detected in the ischemic penumbra. In parallel in vitro co-culture experiments, we found that Notch1 knockdown in microglial BV2 cells inhibited anoxia/reoxygenation-induced JAK2/STAT3 activation and pyroptosis in hippocampal neuron HT22 cells. Conclusions: Our findings elucidate the underlying mechanism of the myeloid Notch1 signaling pathway in regulating neuronal pyroptosis in CIRI, suggesting that targeting myeloid-specific Notch1 is an effective strategy for the treatment of ischemic stroke. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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12 pages, 3800 KiB  
Article
Asymmetry of Lacunae between Brain Hemispheres Is Associated with Atherosclerotic Occlusions of Middle Cerebral Artery
by Lingshan Wu, Hao Huang, Zhiyuan Yu, Xiang Luo and Shabei Xu
Brain Sci. 2023, 13(7), 1016; https://doi.org/10.3390/brainsci13071016 - 30 Jun 2023
Cited by 1 | Viewed by 1912
Abstract
Cerebral small vessel disease (CSVD) commonly coexists with intracranial atherosclerotic stenosis (ICAS). Previous studies have tried to evaluate the relationship between ICAS and CSVD; however, they have yielded varied conclusions. Furthermore, the methodology of these studies is not very rigorous, as they have [...] Read more.
Cerebral small vessel disease (CSVD) commonly coexists with intracranial atherosclerotic stenosis (ICAS). Previous studies have tried to evaluate the relationship between ICAS and CSVD; however, they have yielded varied conclusions. Furthermore, the methodology of these studies is not very rigorous, as they have evaluated the association between ICAS and CSVD of bilateral hemispheres rather than the affected hemisphere. Unilateral middle cerebral artery atherosclerotic occlusion (uni-MCAO) is a favorable model to solve this problem. Material and methods: Patients with uni-MCAO were retrospectively observed. Imaging characteristics, including lacunae, white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs), were compared between the hemisphere ipsilateral to the MCAO and the contralateral hemisphere. Results: A total of 219 patients (median age 57 years; 156 males) were enrolled. Compared with the contralateral side, increased quality of lacunae (median, IQR, 0, 2 vs. 0, 1; p < 0.001) and elevated CSVD score (median, IQR, 0, 1 vs. 0, 1; p = 0.004) were found in the occluded hemisphere. No significant differences were shown for WMH, EPVS, and CMBs. Conclusions: Uni-MCAO has a higher prevalence of lacunae in the ipsilateral hemisphere. However, no interhemispheric differences in WMH, EPVS, or CMBs were found. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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11 pages, 830 KiB  
Article
Association between High-Sensitivity C-Reactive Protein and Blood Pressure Variability in Subacute Stage of Ischemic Stroke
by Chuanli Xu, Zhiyong Fu, Wei Wu, Jin Zhang, Meitong Liu and Lianbo Gao
Brain Sci. 2023, 13(7), 998; https://doi.org/10.3390/brainsci13070998 - 28 Jun 2023
Cited by 2 | Viewed by 1611
Abstract
The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients [...] Read more.
The determinants of blood pressure variability (BPV) are complex. We aimed to evaluate whether circulating high-sensitivity C-reactive protein (hsCRP) is associated with short-term BPV during the subacute stage of ischemic stroke. In this observational study, a consecutive series of acute ischemic stroke patients who underwent 24 h ambulator blood pressure monitoring (ABPM) during day 4 to 10 after onset were enrolled. Multivariable linear regression models were constructed to assess relationships between hsCRP and BPV. Among a total of 325 patients analyzed, the mean age was 60 years old and 72% were male. The SD, CV, ARV of 24 h SBP and DBP were more likely to be higher in patients with hsCRP ≥ 2 mg/L, and these predispositions remained unchanged in linear regression analyses after adjusting for possible confounding factors, with a dose-response relationship when patients were additionally categorized into quartiles according to hsCRP levels using the lowest quartile as a reference category. In contrast, similar results were observed for the mean of SBP but not the mean of DBP. These results indicate that hsCRP is dose-dependently associated with short-term BPV during the subacute stage of ischemic stroke. These findings suggested that patients with a higher level of hsCRP tended to have larger blood pressure fluctuations. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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8 pages, 1336 KiB  
Communication
Neural Injury of the Dopaminergic Pathways in Patients with Middle Cerebral Artery Territory Infarct: A Diffusion Tensor Imaging Study
by Jeong Pyo Seo and Heun Jae Ryu
Brain Sci. 2023, 13(6), 927; https://doi.org/10.3390/brainsci13060927 - 8 Jun 2023
Cited by 3 | Viewed by 1769
Abstract
The mesocortical tract (MCT) and mesolimbic tract (MLT), dopaminergic pathways originating from the ventral tegmental area in the midbrain to the ventral striatum (nucleus accumbens) and prefrontal cortex, play a crucial role in regulating incentive salience. This study aimed to investigate the potential [...] Read more.
The mesocortical tract (MCT) and mesolimbic tract (MLT), dopaminergic pathways originating from the ventral tegmental area in the midbrain to the ventral striatum (nucleus accumbens) and prefrontal cortex, play a crucial role in regulating incentive salience. This study aimed to investigate the potential changes in the MCT and MLT pathways following ischemic stroke, such as middle cerebral artery (MCA) infarction. We enrolled thirty-six patients with MCA infarction and forty healthy individuals with no history of psychiatric or neurological disorders. Using diffusion tensor tractography, we examined the injury to the affected and unaffected MCT and MLT pathways in patients with MCA infarction, comparing them to the control group. Our findings revealed a significant difference in the mean values of fractional anisotropy (FA) and tract volume (TV) of the MCT and MLT pathways between the patient and control groups (p < 0.05). Specifically, the mean FA of the MCT and MLT showed a decrease of 7.94% and 6.33%, respectively, in the affected side compared to the control group (p < 0.05). Similarly, the mean TV of the MCT and MLT showed a decrease of 73.22% and 78.79%, respectively, in the affected side compared to the control group (p < 0.05). These changes were significantly different from those of the unaffected MCT, MLT, and control groups (p < 0.05). Our study suggests that MCA infarction can cause significant damage to the affected MCT and MLT pathways, potentially contributing to our understanding of the pathophysiology of post-stroke depression. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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Review

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14 pages, 429 KiB  
Review
Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease
by Qianqian Kong, Xinxin Xie, Ziyue Wang, Yi Zhang, Xirui Zhou, Lingshan Wu, Zhiyuan Yu, Hao Huang and Xiang Luo
Brain Sci. 2024, 14(3), 269; https://doi.org/10.3390/brainsci14030269 - 12 Mar 2024
Cited by 5 | Viewed by 2558
Abstract
Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers [...] Read more.
Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood–brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood–brain barrier function. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
10 pages, 283 KiB  
Review
Current Knowledge about Headaches Attributed to Ischemic Stroke: Changes from Structure to Function
by Xinxin Xie, Yi Zhang, Qianqian Kong, Hao Huang, Zhiyuan Yu, Xiang Luo and Wensheng Qu
Brain Sci. 2023, 13(7), 1117; https://doi.org/10.3390/brainsci13071117 - 23 Jul 2023
Cited by 1 | Viewed by 2434
Abstract
Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and [...] Read more.
Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and structural lesions in the cerebral cortex, subcortical white matter, deep gray matter nuclei, brainstem, and cerebellum. However, the substantial heterogeneity of IS, subjective evaluations of headaches, and inadequate cohort studies make it difficult to explore the pathophysiology of headaches attributed to IS. In our recommendation, favorable imaging techniques, such as magnetic resonance imaging and positron emission tomography, may provide new insights into mechanical studies of IS headaches from structure to function. It may also be helpful to extend the research field by targeting several shared signal transducers between headaches and IS. These markers might be neuropeptides, vasoactive substances, ion channels, or electrophysiologic changes. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
13 pages, 284 KiB  
Review
Early Brain Injury and Neuroprotective Treatment after Aneurysmal Subarachnoid Hemorrhage: A Literature Review
by Xiaopeng Li, Lang Zeng, Xuanzhen Lu, Kun Chen, Maling Yu, Baofeng Wang and Min Zhao
Brain Sci. 2023, 13(7), 1083; https://doi.org/10.3390/brainsci13071083 - 17 Jul 2023
Cited by 17 | Viewed by 2774
Abstract
Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, [...] Read more.
Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood–brain barrier disruption, immune–inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia–hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
10 pages, 445 KiB  
Review
A Review of Artificial Intelligence in the Rupture Risk Assessment of Intracranial Aneurysms: Applications and Challenges
by Xiaopeng Li, Lang Zeng, Xuanzhen Lu, Kun Chen, Maling Yu, Baofeng Wang and Min Zhao
Brain Sci. 2023, 13(7), 1056; https://doi.org/10.3390/brainsci13071056 - 11 Jul 2023
Cited by 6 | Viewed by 2702
Abstract
Intracranial aneurysms (IAs) are highly prevalent in the population, and their rupture poses a significant risk of death or disability. However, the treatment of aneurysms, whether through interventional embolization or craniotomy clipping surgery, is not always safe and carries a certain proportion of [...] Read more.
Intracranial aneurysms (IAs) are highly prevalent in the population, and their rupture poses a significant risk of death or disability. However, the treatment of aneurysms, whether through interventional embolization or craniotomy clipping surgery, is not always safe and carries a certain proportion of morbidity and mortality. Therefore, early detection and prompt intervention of IAs with a high risk of rupture is of notable clinical significance. Moreover, accurately predicting aneurysms that are likely to remain stable can help avoid the risks and costs of over-intervention, which also has considerable social significance. Recent advances in artificial intelligence (AI) technology offer promising strategies to assist clinical trials. This review will discuss the state-of-the-art AI applications for assessing the rupture risk of IAs, with a focus on achievements, challenges, and potential opportunities. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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8 pages, 251 KiB  
Review
Animal Models of Ischemic Stroke with Different Forms of Middle Cerebral Artery Occlusion
by Lang Zeng, Shengqi Hu, Lingcheng Zeng, Rudong Chen, Hua Li, Jiasheng Yu and Hongkuan Yang
Brain Sci. 2023, 13(7), 1007; https://doi.org/10.3390/brainsci13071007 - 29 Jun 2023
Cited by 21 | Viewed by 5589
Abstract
Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical [...] Read more.
Ischemic stroke is a common type of stroke that significantly affects human well-being and quality of life. In order to further characterize the pathophysiology of ischemic stroke and develop new treatment strategies, ischemic stroke models with controllable and consistent response to potential clinical treatments are urgently needed. The middle cerebral artery occlusion (MCAO) model is currently the most widely used animal model of ischemic stroke. This review discusses various methods for constructing the MCAO model and compares their advantages and disadvantages in order to provide better approaches for studying ischemic stroke. Full article
(This article belongs to the Special Issue Ischemic Brain Injury: Cerebral Metabolism and Imaging)
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