myelin-basic-protein and Brain-Injuries--Traumatic

Astrocytes are critical neuroimmune cells that modulate the neuroinflammatory response following traumatic brain injury (TBI) because of their ability to acquire neurotoxic (A1) or neuroprotective (A2) phenotypes. Using C34, a novel pharmacologic Toll-like receptor (TLR) 4 inhibitor, we explored their respective polarization states after TBI.. A murine controlled cortical impact model was used, and the results were analyzed on postinjury days (PIDs) 1, 7, and 28. The experimental groups are as follows: (1) sham, (2) sham + C34, (3) TBI, and (4) TBI + C34. Quantitative real-time polymerase chain reaction was used to quantify gene expression associated with proinflammatory (A1) and anti-inflammatory (A2) phenotypes. Morris water maze was used to assess neurocognitive outcomes. Fixed frozen cortical samples were sectioned, stained for myelin basic protein and 4',6-diamidino-2-phenylindole, and then imaged. Student t test and one-way analysis of variance were used for statistical analysis with significance achieved when p < 0.05.. On quantitative real-time polymerase chain reaction, C34-treated groups showed a significant decrease in the expression of A1 markers such as Gbp2 and a significant increase in the expression of A2 markers such as Emp1 when compared with untreated groups on PID 1. On PIDs 7 and 28, the expression of most A1 and A2 markers was also significantly decreased in the C34-treated groups. On immunohistochemistry, C34-treated groups demonstrated increased myelin basic protein staining into the lesion by PID 28. C34-treated groups showed more platform entries on Morris water maze when compared with untreated groups on PID 7 and PID 28.. Following TBI, early TLR4 blockade modulates astrocytic function and shifts its polarization toward the anti-inflammatory A2-like phenotype. This is accompanied by an increase in myelin regeneration, providing better neuroprotection and improved neurocognitive outcomes. Targeting A1/A2 balance with TLR4 inhibition provides a potential therapeutic target to improve neurobehavioral outcomes in the setting of TBI.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Brain Injuries, Traumatic; Disease Models, Animal; Maze Learning; Mice; Myelin Basic Protein; Toll-Like Receptor 4

Traumatic brain injury (TBI) is a major neurological disorder without FDA-approved therapies. In this study, we have examined the concept that TBI might trigger global brain proteolysis in the acute post-injury phase. Thus, we conducted a systemic proteolytic peptidomics analysis using acute cerebrospinal fluid (CSF) samples from TBI patients and normal control samples. We employed ultrafiltration-based low molecular weight (LMW; < 10 kDa) peptide enrichment, coupled with nano-reversed-phase liquid chromatography/tandem mass spectrometry analysis, followed with orthogonal quantitative immunoblotting-based protein degradation analysis. We indeed identified novel patterns of injury-dependent proteolytic peptides derived from neuronal components (pre- and post-synaptic terminal, dendrites, axons), extracellular matrix, oligodendrocytes, microglial cells, and astrocytes. Among these, post-synaptic protein neurogranin was identified for the first time converted to neurogranin peptides including neurogranin peptide (aa 16-64) that is phosphorylated at Ser-36/48 (P-NG-fragment) in acute human TBI CSF samples vs. normal control with a receiver operating characteristic area under the curve of 0.957. We also identified detailed processing of astroglia protein (vimentin) and oligodendrocyte protein (MBP and Golli-MBP) to protein breakdown products (BDPs) and/or LMW proteolytic peptides after TBI. In addition, using MS/MS selected reaction monitoring method, two C-terminally released MBP peptides TQDENPVVHFF and TQDENPVVHF were found to be elevated in acute and subacute TBI CSF samples as compared to their normal control counterparts. These findings imply that future therapeutic strategies might be placed on the suppression of brain proteolysis as a target. The endogenous proteolytic peptides discovered in human TBI biofluid could represent useful diagnostic and monitoring tools for TBI.

Topics: Biomarkers; Brain Injuries, Traumatic; Humans; Myelin Basic Protein; Neurogranin; Peptides; Proteolysis; Tandem Mass Spectrometry; Vimentin

In forensic pathology, traumatic brain injury (TBI) is a frequently encountered cause of death. Unfortunately, the statistic autopsy data, risk investigation about injury patterns, and circumstances of TBI are still sparse. Estimates of survival time post-TBI and postmortem diagnosis of TBI are especially important implications in forensic medicine. Neurogranin (Ng) and myelin basic protein (MBP) represent potential biomarkers of TBI. The present study analyzed retrospectively the forensic autopsy records of TBI cases at a university center of medico-legal investigation from 2008 to 2020. Immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to investigate the expression changes of Ng and MBP in the cortical brain injury adjacent tissues and serum, respectively, from cases of TBI at autopsy with different survival times post-TBI. The results show that the major mechanism of death of TBI is assault, and accident was the major manner of death. Ng and MBP are mainly expressed in the cortical nerve cells and the myelin sheath, respectively. The serum levels of Ng and MBP in each TBI group were higher compared with those in the controls. The brain cortical levels of Ng and MBP decreased at first and then steadily increased with extended survival time post-TBI. The immunopositive ratios and serum concentration of Ng and MBP have shown significant differences among control group and all TBI group (p < 0.001). Collectively, the immunohistochemical analyses of Ng and MBP in human brain tissues may be useful to determine the survival time after TBI, and Ng and MBP level in the human blood specimens could be considered as a postmortem diagnostic tools of TBI in forensic practice.

Topics: Autopsy; Biomarkers; Brain Injuries; Brain Injuries, Traumatic; Humans; Myelin Basic Protein; Neurogranin; Retrospective Studies

To study the content of antibodies to the basic protein of myelin IgM in the blood of children with traumatic brain injury for a comprehensive assessment of the severity and prediction of outcomes of TBI.. 81 children with traumatic brain injury (TBI) of varying severity and 29 children of the comparison group aged 2 months to 18 years were examined, in whom the content of IgM antibodies in blood plasma was determined.. In groups of children with different severity of TBI, the average content of IgM antibodies in the blood is higher than in children of the comparison group, and the values of IgM antibodies correlate with the severity of TBI. In children with moderate TBI, the average level of IgM antibodies in the blood is significantly higher than in children with mild TBI, and in children with severe TBI, the average level of IgM antibodies in the blood is significantly higher than in children with moderate TBI. A repeated study found a significant decrease in the average content of IgM antibodies in severe TBI in children without post-traumatic epilepsy compared to their average content in children with post-traumatic epilepsy.. Normalization (elimination) of IgM antibodies in children in the late period of TBI is associated with a prognostically favorable course of the autoimmune process in the brain; its absence indicates a prolonged autoimmune process. After TBI, it is recommended to include in the examination of children an immunological study of the content of antibodies to the basic protein of myelin IgM in the blood, the indicators of which, in combination with other data, make it possible to predict the outcomes of TBI.. Изучение содержания антител к основному белку миелина IgM в крови детей с черепно-мозговой травмой (ЧМТ) для оценки тяжести заболевания и прогнозирования его исходов.. Обследован 81 ребенок с ЧМТ различной степени тяжести и 29 детей группы сравнения в возрасте от 2 мес до 18 лет, у которых определялось содержание антител IgM в плазме крови.. У детей с различной тяжестью ЧМТ средняя концентрация IgM в крови более высокая, чем в группе сравнения. Уровень IgM коррелирует со степенью тяжести ЧМТ. У детей с ЧМТ средней степени тяжести содержание в крови IgM достоверно выше, чем у детей с легкой ЧМТ, а у детей с тяжелой ЧМТ содержание в крови IgM достоверно выше, чем у детей ЧМТ средней степени тяжести. Повторное обследование выявило достоверно меньшее содержание IgM при тяжелой ЧМТ у детей без посттравматической эпилепсии по сравнению с их концентрацией у детей с посттравматической эпилепсией.. Нормализация уровня IgM у детей в отдаленном периоде ЧМТ связана с благоприятным течением аутоиммунного процесса в головном мозге; ее отсутствие свидетельствует о пролонгированном аутоиммунном процессе. После ЧМТ у детей целесообразно определять содержание в крови антител к основному белку миелина, показатели которых в комплексе с другими данными позволяют прогнозировать исходы ЧМТ.

Topics: Brain Injuries, Traumatic; Child; Epilepsy, Post-Traumatic; Humans; Immunoglobulin M; Myelin Basic Protein; Prognosis

Traumatic brain injury (TBI) is a common phenomenon, accounting for significant cost and adverse health effects. While there is information about focal pathologies following TBI, knowledge of more diffuse processes is lacking, particularly regarding how analgesics affect this pathology. As buprenorphine is the most commonly used analgesic in experimental TBI models, this study investigated the acute effects of the opioid analgesic buprenorphine (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. We utilized a model of central fluid percussion injury (CFPI) in adult male rats treated with a single subcutaneous bolus of Bup-SR-Lab or saline 15 min post-injury. Microscopic assessments were performed at 1 day post-injury. Cell impermeable dextran was infused intraventricularly prior to sacrifice to assess neuronal membrane disruption. Axonal injury was assessed by investigating labeling of the anterogradely transported amyloid precursor protein. Neuroinflammation was assessed by analyzing Iba-1 + microglial and GFAP + astrocyte histological/morphological features as well as cytokine levels in both regions of interest (ROIs). Myelin pathology was assessed by evaluating the expression of myelin basic protein (MBP) and the propensity of MBP + myelin debris. Acute physiologic data showed no difference between groups except for reduction in weight loss following cFPI in Bup treated animals compared to saline. There were no discernable differences in axonal injury or membrane disruption between treatment groups. Cytokine levels were consistent between Bup and saline treated animals, however, microglia and astrocytes revealed region specific histological changes at 1d following Bup treatment. Myelin integrity and overall MBP expression showed no differences between Bup and saline treated animals, but there were significant regional differences in MBP expression between the cortex and thalamus. These data suggest effects of Bup treatment on weight following CFPI and potential regional specificity of Bup-associated microglial and astrocyte alterations, but very little change in other acute pathology at 1-day post-injury. Overall, this preliminary study indicates that use of Bup-SR-Lab in preclinical work does have effects on acute glial pathology, however, longer term studies will be needed to assess potential effects of Bup treatment on more chronic pathological progressions.

Topics: Amyloid beta-Protein Precursor; Analgesics, Opioid; Animals; Astrocytes; Brain Injuries, Diffuse; Brain Injuries, Traumatic; Buprenorphine; Cytokines; Male; Microglia; Myelin Basic Protein; Myelin Sheath; Neuroglia; Rats; Rats, Sprague-Dawley

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury.

Topics: Adult; Aged; Aged, 80 and over; Autopsy; Biomarkers; Brain Injuries, Traumatic; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Male; Middle Aged; Myelin Basic Protein; Neurofilament Proteins

Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of ac

Topics: Animals; Antigens, Surface; Blood-Brain Barrier; Brain Injuries, Traumatic; Caspase 3; Disease Models, Animal; Humans; Microvessels; Myelin Basic Protein; Myelin Sheath; Rats; Rats, Sprague-Dawley; Thalamus; Up-Regulation

The release of brain-originated peptides such as tau protein (MAPT), S-100β, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) into the cerebrospinal fluid (CSF) has been positively correlated with head injuries in clinical and basic research. In this study, we wanted to examine if selected CSF biomarkers (GFAP, NFL, and myelin basic protein - MBP) of head injury may be useful in post-mortem examination and diagnosis of forensic cases. The study was carried out using cases of head injury and cases of sudden death (cardiopulmonary failure, no injuries of the head as control group) provided by forensic pathologists at the Department of Forensic Medicine, Medical University of Warsaw. Cerebrospinal fluid was collected within 24 h after death using suboccipital puncture. The concentration of these peptides was compared using an enzyme-linked immunosorbent assay (ELISA). Brain specimens (frontal cortex) were collected during forensic autopsies. Sections were stained immunohistochemically against GFAP, MBP, NF, and amyloid-β precursor protein (APP). As a result we documented that elevated levels of CSF, GFAP, MBP, and NFL should be considered a marker for severe and moderate traumatic brain injury. Elevated levels of those peptides combined with a negative APP staining point to their role as markers of head trauma with a shorter time span than APP (manner of minutes).

Topics: Adult; Autopsy; Biomarkers; Brain Injuries, Traumatic; Female; Glial Fibrillary Acidic Protein; Humans; Male; Middle Aged; Myelin Basic Protein; Neurofilament Proteins

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three mTBI. This study of acute events following closed head mTBI identifies lipid peroxidation in neurons at the same time as cognitive deficits. Our study adds to existing literature, providing biomechanics data and demonstrating mild cognitive disturbances associated with diffuse injury, predominantly to grey matter, acutely following repeated mTBI.

Topics: Aldehydes; Animals; Antigens; Blood-Brain Barrier; Brain; Brain Injuries, Traumatic; Calcium-Binding Proteins; Cell Death; Cognition Disorders; Cohort Studies; Disease Models, Animal; Female; Glial Fibrillary Acidic Protein; Lipid Peroxidation; Microfilament Proteins; Myelin Basic Protein; Neurologic Examination; Neurons; Oligodendrocyte Transcription Factor 2; Oxidative Stress; Proteoglycans; Rats; Time Factors

Traumatic brain injury (TBI) encompasses a broad range of injury mechanisms and severity. A detailed determination of TBI severity can be a complex challenge, with current clinical tools sometimes insufficient to tailor a clinical response to a spectrum of patient needs. Blood biomarkers of TBI may supplement clinical assessments but currently available biomarkers have limited sensitivity and specificity. While oxidative stress is known to feature in damage mechanisms following TBI, investigation of blood biomarkers of oxidative stress has been limited. This exploratory pilot study of a subset of 18 trauma patients with TBI of varying severity, quantifies circulating concentrations of the structural damage indicators S100b, and myelin basic protein (MBP), and the biomarkers of oxidative stress hydroxynonenal (HNE), malondialdehyde (MDA), carboxy-methyl-lysine (CML), and 8-hydroxy-2'-deoxy-guanosine (8-OHDG). Significant increases in circulating S100b, MBP, and HNE were observed in TBI patient samples compared to 8 uninjured controls, and there was a significant decrease in CML. This small exploratory study supports the current literature on S100b and MBP elevation in TBI, and reveals potential for the use of peripheral oxidative stress markers to assist in determination of TBI severity. Further investigation is required to validate results and confirm trends.

Topics: Adult; Aldehydes; Biomarkers; Brain Injuries, Traumatic; Female; Humans; Male; Myelin Basic Protein; Oxidative Stress; Pilot Projects; Prospective Studies; S100 Calcium Binding Protein beta Subunit; Treatment Outcome

The interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells.. Totally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis.. The levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C.. Intrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.

Topics: Animals; Anti-Inflammatory Agents; Antigens, Surface; Brain Injuries, Traumatic; CD4-CD8 Ratio; Coculture Techniques; Male; Mice; Mice, Inbred C57BL; Microglia; Myelin Basic Protein; T-Lymphocytes

Objective reliable markers to assess traumatic brain injury (TBI) and predict outcome soon after injury are a highly needed tool for optimizing management of pediatric TBI. We assessed serum concentrations of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in a cohort of 45 children with clinical diagnosis of TBI (Glasgow Coma Scale [GCS] 3-15) and 40 healthy subjects, evaluated their associations with clinical characteristics and outcomes, and compared their performance to previously published data on two well-studied blood biomarkers, S100B and MBP. We observed higher serum levels of GFAP and UCH-L1 in brain-injured children compared with controls and also demonstrated a step-wise increase of biomarker concentrations over the continuum of severity from mild to severe TBI. Furthermore, while we found that only the neuronal biomarker UCH-L1 holds potential to detect acute intracranial lesions as assessed by computed tomography (CT), both markers were substantially increased in TBI patients even with a normal CT suggesting the presence of undetected microstructural injuries. Serum UCH-L1 and GFAP concentrations also strongly predicted poor outcome and performed better than S100B and MBP. Our results point to a role of GFAP and UCH-L1 as candidate biomarkers for pediatric TBI. Further studies are warranted.

Topics: Biomarkers; Brain Injuries, Traumatic; Case-Control Studies; Child; Child, Preschool; Female; Glial Fibrillary Acidic Protein; Humans; Male; Myelin Basic Protein; Prospective Studies; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Treatment Outcome; Ubiquitin Thiolesterase

Traumatic brain injury (TBI) is a major cause of death and disability in young adults. Long-term mental disability often occurs in patients suffering moderate and severe TBI while not as frequent in the victims of mild TBI. To explore the potential mechanism underlying this severity-dependent cognitive deficit, we subjected C57/BL6 mice to different severities of controlled cortical impact (CCI) and assessed their learning-memory functions. The mice subjected to moderate and severe TBI exhibited significantly impaired long-term spatial learning-memory ability, which was accompanied by marked white matter injury and hippocampus damage. In contrast, long-term learning-memory deficits or structural abnormalities within the hippocampus or white matter were not significant in the case of mild TBI. According to a correlation analysis, the hippocampus or white matter injury severity was more relevant to Morris water maze outcome than tissue volume. This study revealed that long-term spatial learning-memory deficits are dependent on the severity of destruction in the white matter and hippocampus. Therapeutic strategies targeting both the white matter and hippocampus may be needed to improve the neurological functions in TBI victims.

Topics: Animals; Brain Injuries, Traumatic; Disease Models, Animal; Hippocampus; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Neurofilament Proteins; Neurons; Severity of Illness Index; Spatial Learning