Search Results (12)

Background/Objectives: Traumatic brain injury (TBI) occurs after a sudden mechanical force to the skull and represents a significant public health problem. Initial brain trauma triggers secondary pathophysiological processes that induce structural and functional impairment of the central nervous system, even in the regions distant to the lesion site. Later in life, these changes can be manifested as neurodegenerative sequalae that commonly involve proteinopathies, such as transactive DNA-binding protein 43 (TDP-43). The progression of pathophysiological changes to the spinal cord motor neurons has been detected after repetitive TBI, while such changes have been less investigated after single TBI. Methods: Single TBI was applied over the left parietal cortex of mice by using the lateral fluid percussion injury apparatus and a separate cohort of animals received repetitive mild TBI by weight drop apparatus, with two mild injuries daily, for five days in a row. Mice were sacrificed after single moderate or last mild TBI and their spinal cords were prepared for the analyses. For both types of injury, sham-injured mice were used as a control group. Results: Here, we found an early formation of toxic phosphorylated TDP-43 species on the 3rdday post-injury which, together with TDP-43 cytoplasmic translocation, remained present in the subacute period of 14 days after repetitive mild but not single moderate TBI. During the subacute period following a repetitive brain trauma, we found an increased choline acetyltransferase protein expression and significant microgliosis in the cervical part of the spinal cord, which was not detected after single TBI. Astrogliosis presented similarly after both experimental procedures. Conclusions: This study demonstrates the differences in the spinal cord TDP-43 pathology and inflammation, depending on the brain trauma type, and may contribute to the development of targeted therapeutic strategies. Full article

Whether brain temperature noninvasively extracted by magnetic resonance imaging has a role in identifying brain changes in the later phases of mild to moderate traumatic brain injury (TBI) is not known. This prospective study aimed to evaluate if TBI patients in subacute and chronic phases had altered brain temperature measured by whole-brain magnetic resonance spectroscopic imaging (WB-MRSI) and if the measurable brain temperature had any relationship with cognitive function scores. WB-MRSI was performed on eight TBI patients and fifteen age- and sex-matched control subjects. Brain temperature (T) was extracted from the brain’s major metabolites and compared between the two groups. The T of the patients was tested for correlation with cognitive function test scores. The results showed significantly lower brain temperature in the TBI patients (p < 0.05). Brain temperature derived from N-acetylaspartate (T_NAA) strongly correlated with the 2 s paced auditory serial addition test (PASAT-2s) score (p < 0.05). The observation of lower brain temperature in TBI patients may be due to decreased metabolic activity resulting from glucose and oxygen depletion. The correlation of brain temperature with PASAT-2s may imply that noninvasive brain temperature may become a noninvasive index reflecting cognitive performance. Full article

Traumatic brain injury (TBI) is a major contributor to morbidity and mortality in the United States as several million people visit the emergency department every year due to TBI exposures. Unfortunately, there is still no consensus on the pathology underlying mild TBI, the most common severity sub-type of TBI. Previous preclinical and post-mortem human studies have detailed the presence of diffuse axonal injury following TBI, suggesting that white matter pathology is the predominant pathology of diffuse brain injury. However, the inertial loading produced by TBI results in strain fields in both gray and white matter. In order to further characterize gray matter pathology in mild TBI, our lab used a pig model (n = 25) of closed-head rotational acceleration-induced TBI to evaluate blood-brain barrier disruptions, neurodegeneration, astrogliosis, and microglial reactivity in the cerebral cortex out to 1 year post-injury. Immunohistochemical staining revealed the presence of a hyper-ramified microglial phenotype—more branches, junctions, endpoints, and longer summed process length—at 30 days post injury (DPI) out to 1 year post injury in the cingulate gyrus (p < 0.05), and at acute and subacute timepoints in the inferior temporal gyrus (p < 0.05). Interestingly, we did not find neuronal loss or astroglial reactivity paired with these chronic microglia changes. However, we observed an increase in fibrinogen reactivity—a measure of blood-brain barrier disruption—predominately in the gray matter at 3 DPI (p = 0.0003) which resolved to sham levels by 7 DPI out to chronic timepoints. Future studies should employ gene expression assays, neuroimaging, and behavioral assays to elucidate the effects of these hyper-ramified microglia, particularly related to neuroplasticity and responses to potential subsequent insults. Further understanding of the brain’s inflammatory activity after mild TBI will hopefully provide understanding of pathophysiology that translates to clinical treatment for TBI. Full article

Mild blast-induced traumatic brain injury (bTBI) is a modality of injury that has been of major concern considering a large number of military personnel exposed to explosive blast waves. bTBI results from the propagation of high-pressure static blast forces and their subsequent energy transmission within brain tissue. Exposure to this overpressure energy causes a diffuse injury that leads to acute cell damage and, if chronic, leads to detrimental long-term cognitive deficits. The literature presents a neuro-centric approach to the role of mitochondria dynamics dysfunction in bTBI, and changes in astrocyte-specific mitochondrial dynamics have not been characterized. The balance between fission and fusion events is known as mitochondrial dynamics. As a result of fission and fusion, the mitochondrial structure is constantly altering its shape to respond to physiological stimuli or stress, which in turn affects mitochondrial function. Astrocytic mitochondria are recognized to play an essential role in overall brain metabolism, synaptic transmission, and neuron protection. Mitochondria are vulnerable to injury insults, leading to the increase in mitochondrial fission, a mechanism controlled by the GTPase dynamin-related protein (Drp1) and the phosphorylation of Drp1 at serine 616 (p-Drp1^s616). This site is critical to mediate the Drp1 translocation to mitochondria to promote fission events and consequently leads to fragmentation. An increase in mitochondrial fragmentation could have negative consequences, such as promoting an excessive generation of reactive oxygen species or triggering cytochrome c release. The aim of the present study was to characterize the unique pattern of astrocytic mitochondrial dynamics by exploring the role of DRP1 with a combination of in vitro and in vivo bTBI models. Differential remodeling of the astrocytic mitochondrial network was observed, corresponding with increases in p-Drp1^S616 four hours and seven days post-injury. Further, results showed a time-dependent reactive astrocyte phenotype transition in the rat hippocampus. This discovery can lead to innovative therapeutics targets to help prevent the secondary injury cascade after blast injury that involves mitochondria dysfunction. Full article

Subdural haemorrhage (SDH) as result of a traumatic brain injury (TBI) is a common cause of death in cases of fatal physical abuse. Since intracranial bleeding is a common finding in elderly due to age-related intracranial changes or increasing prevalence of anticoagulant medication, differential diagnosis between inflicted and non-inflicted head injury is challenging. A case of an elderly woman’s death caused by TBI is reported. Autopsy showed multiple polychromatic bruises and a frontoparietal hematoma with bilateral subacute SDH. History excluded paraphysiological or pathological non-traumatic conditions that could justify SDH, while iatrogenic factors only played a contributory role. Since polychromatic bruises distributed on the face, the upper extremities and the chest were consistent with forceful grasping/gripping or repeated blows and SDH can form in absence of impact or by mild/minor blows, SDH was considered the result of repeated physical abuses. Differential diagnosis between traumatic and non-traumatic SDH is still challenging for forensic pathologists. As largely accepted in the pediatric population and occasionally described also in adults, however, violent shaking should be also considered as a possible mechanism of SDH—especially in elderly who do not have any sign of impact to the head. Full article

Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions. Full article

Rationale: Posttraumatic epilepsy (PTE) is a common cause of morbidity in children after a traumatic brain injury (TBI), occurring in 10–20% of children following severe TBI. PTE is diagnosed after two or more unprovoked seizures occurring 1-week post TBI. More often, studies have focused on children with epilepsy due to severe TBI. We aim to understand the utility of head computed tomography (HCT), EEG, and the risk of developing drug-resistant epilepsy in children after mild TBI. Method: We retrospectively studied 321 children with TBI at a tertiary pediatric referral center during a 10-year period. Mild TBI was defined as loss of consciousness (LOC) or amnesia < 30 min, moderate TBI as LOC or amnesia between 30 min and 1 day, and severe TBI as LOC or amnesia > 1 day, subdural hemorrhage, or contusion. Multiple clinical variables were reviewed, including past and present antiepileptic drug(s), seizure control, and mode of injury. First and subsequent post-TBI EEGs/prolonged video-EEGs were obtained acutely, subacutely, and/or chronically (range, day 1–3 years, median 1 month). Descriptive analyses were conducted using medians and ranges for continuous data. Categorical data were reported using frequencies and percentages, while comparisons between groups were made using Fisher’s exact test for small sample sizes. Results: Forty-seven children were diagnosed with posttraumatic epilepsy: eight children (17%) due to mild TBI, 39 children (83%) due to severe TBI. For the eight children with mild TBI whom all had an accidental trauma (non-inflicted), the median follow-up time was 25 months (range 1.5 months–84 months). The median age was 10 years (range 4–18 years), and the median age at the time of injury was seven years (range: 23 months–13 years). No relevant previous medical history was present for six patients (80%), and two patients’ (20%) relevant previous medical histories were unknown. Seven patients (88%) had no history of seizures, and patient #6 (12%) had unknown seizure history. Six patients (75%) had normal routine EEG(s). Patient #6 (13%) had an abnormal VEEG 3 months after the initial normal routine EEG, while patient #1 (13%) had an initial prolonged EEG 8 months after TBI. Compared to the 39 patients with severe TBI, 31 (79%) of whom had abnormal EEGs (routine and/or prolonged with video), mild TBI patients were more likely to have normal EEGs, p = 0.005. Head CT scans were obtained acutely for seven patients (90%), all of which were normal. One patient only had brain magnetic resonance imaging (MRI) 8 months after the injury. Compared to the 39 patients with severe TBI, all of whom had abnormal HCTs, mild TBI patients were less likely to have abnormal HCTs, p < 0.0001. In patients with mild TBI, no patient had both abnormal EEG/VEEG and HCT, and no one was on more than one Antiepileptic drug (AED), p < 0.005. Six patients (75%) had MRIs, of which five (63%) were normal. Two patients (#1, 7) did not have MRIs, while one patient’s (#4) MRI was unavailable. Five patients (63%) had a seizure <24 h post TBI, while the rest had seizures after the first week of injury. Conclusion: Children with epilepsy due to mild TBI, loss of consciousness, or amnesia < 30 min are more likely to have normal HCT and EEG and to be on 0–1 AED. Limitations of our study include the small sample size and retrospective design. The current findings add to the paucity of data in children who suffer from epilepsy due to mild TBI. Full article

Traumatic brain injury (TBI) is a disabling disorder and a major cause of death and disability in the world. Both single and repetitive traumas affect the brain acutely but can also lead to chronic neurodegenerative changes. Clinical studies have shown some dissimilarities in transactive response DNA binding protein 43 (TDP-43) expression patterns following single versus repetitive TBI. We explored the acute cortical post-traumatic changes of TDP-43 using the lateral fluid percussion injury (LFPI) model of single moderate TBI in adult male mice and investigated the association of TDP-43 with post-traumatic neuroinflammation and synaptic plasticity. In the ipsilateral cortices of animals following LFPI, we found changes in the cytoplasmic and nuclear levels of TDP-43 and the decreased expression of postsynaptic protein 95 within the first 3 d post-injury. Subacute pathological changes of TDP-43 in the hippocampi of animals following LFPI and in mice exposed to repetitive mild TBI (rmTBI) were studied. Changes in the hippocampal TDP-43 expression patterns at 14 d following different brain trauma procedures showed pathological alterations only after single moderate, but not following rmTBI. Hippocampal LFPI-induced TDP-43 pathology was not accompanied by the microglial reaction, contrary to the findings after rmTBI, suggesting that different types of brain trauma may cause diverse pathophysiological changes in the brain, specifically related to the TDP-43 protein as well as to the microglial reaction. Taken together, our findings may contribute to a better understanding of the pathophysiological events following brain trauma. Full article

Traumatic brain injury (TBI) can be defined as a disorder in the function of the brain after a bump, blow, or jolt to the head, or penetrating head injury. Mild traumatic brain injury (mTBI) can cause devastating effects, such as the initiation of long-term neurodegeneration in brain tissue. In the current study, the effects of mTBI were investigated on rat brain regions; cortex (Co) and corpus callosum (CC) after 24 h (subacute trauma) by Fourier transform infrared (FTIR) imaging and immunohistochemistry (IHC). IHC studies showed the formation of amyloid-β (Aβ) plaques in the cortex brain region of mTBI rats. Moreover, staining of myelin basic protein presented the shearing of axons in CC region in the same group of animals. According to FTIR imaging results, total protein and lipid content significantly decreased in both Co and CC regions in mTBI group compared to the control. Due to this significant decrease in both lipid and protein content, remarkable consistency in lipid/protein band ratio in mTBI and control group, was observed. Significant decrease in methyl content and a significant increase in olefinic content were observed in Co and CC regions of mTBI rat brain tissues. Classification amongst distinguishable groups was performed using principal component analysis (PCA) and hierarchical clustering (HCA). This study established the prospective of FTIR imaging for assessing biochemical changes due to mTBI with high sensitivity, precision and high-resolution. Full article

Objective: Attentional problems are amongst the most commonly reported complaints following mild traumatic brain injury (mTBI), including difficulties orienting and disengaging attention, sustaining it over time, and dividing attentional resources across multiple simultaneous demands. The objective of this study was to track, using a single novel electrophysiological task, various components associated with the deployment of visuospatial selective attention. Methods: A paradigm was designed to evoke earlier visual evoked potentials (VEPs), as well as attention-related and visuocognitive ERPs. Data from 36 individuals with mTBI (19 subacute, 17 chronic) and 22 uninjured controls are presented. Postconcussion symptoms (PCS), anxiety (BAI), depression (BDI-II) and visual attention (TEA Map Search, DKEFS Trail Making Test) were also assessed. Results: Earlier VEPs (P1, N1), as well as processes related to visuospatial orientation (N2pc) and encoding in visual short-term memory (SPCN), appear comparable in mTBI and control participants. However, there appears to be a disruption in the spatiotemporal dynamics of attention (N2pc-Ptc, P2) in subacute mTBI, which recovers within six months. This is also reflected in altered neuropsychological performance (information processing speed, attentional shifting). Furthermore, orientation of attention (P3a) and working memory processes (P3b) are also affected and remain as such in the chronic post-mTBI period, in co-occurrence with persisting postconcussion symptomatology. Conclusions: This study adds original findings indicating that such a sensitive and rigorous ERP task implemented at diagnostic and follow-up levels could allow for the identification of subtle but complex brain activation and connectivity deficits that can occur following mTBI. Full article

The etiologic basis for sporadic forms of neurodegenerative diseases has been elusive but likely represents the product of genetic predisposition and various environmental factors. Specific gene-environment interactions have become more salient owing, in part, to the elucidation of epigenetic mechanisms and their impact on health and disease. The linkage between traumatic brain injury (TBI) and Parkinson’s disease (PD) is one such association that currently lacks a mechanistic basis. Herein, we present preliminary blood-based metabolomic evidence in support of potential association between TBI and PD. Using untargeted and targeted high-performance liquid chromatography-mass spectrometry we identified metabolomic biomarker profiles in a cohort of symptomatic mild TBI (mTBI) subjects (n = 75) 3–12 months following injury (subacute) and TBI controls (n = 20), and a PD cohort with known PD (n = 20) or PD dementia (PDD) (n = 20) and PD controls (n = 20). Surprisingly, blood glutamic acid levels in both the subacute mTBI (increased) and PD/PDD (decreased) groups were notably altered from control levels. The observed changes in blood glutamic acid levels in mTBI and PD/PDD are discussed in relation to other metabolite profiling studies. Should our preliminary results be replicated in comparable metabolomic investigations of TBI and PD cohorts, they may contribute to an “excitotoxic” linkage between TBI and PD/PDD. Full article

Awareness of mild traumatic brain injury (mTBI) and persisting post-concussive syndrome (PCS) has increased substantially in the past few decades, with a corresponding increase in research on diagnosis, management, and treatment of patients with mTBI. The purpose of this article is to provide a narrative review of the current literature on behavioral assessment and management of patients presenting with mTBI/PCS, and to detail the potential role of neuropsychologists and rehabilitation psychologists in interdisciplinary care for this population during the acute, subacute, and chronic phases of recovery. Full article