Post Traumatic Brain Injury Research Articles

Microfluidic development of brain-derived neurotrophic factor loaded solid lipid nanoparticles: An in vitro evaluation in the post-traumatic brain injury neuroinflammation model

Microfluidic-based nanoscale drug delivery systems have risen to prominence in the field of precision nanomedicine in recent years. This intriguing innovation could provide unique therapeutic prospects in the treatment of serious disorders as traumatic brain injury, a potentially fatal condition that is widespread during childhood. According to current scientific study, neurotrophins are vital for the healing of injured brain parenchyma, and the brain-derived neurotrophic factor (BDNF) in particular may have significant regenerative effects. To address BDNF-related pharmacokinetic constraints, microfluidic-assisted manufacturing of BDNF-loaded solid lipid nanoparticles (BDNF-SLNs) was carried out, and following evaluation, the formulation demonstrated optimum characteristics in terms of size (190.3 ± 10.1 nm), PDI (0.180 ± 0.023), and ζ-potential (– 39.2 ± 1.30 mV). Short-term stability studies and the haemolysis assay verified the formulation's biocompatibility, while an in vitro permeability analysis revealed an increase in the Papp of the encapsulated BDNF (1.27x10−5 cm/s) as compared to plain BDNF (9.31x10−6 cm/s). The in vitro mimicked neuroinflammatory model demonstrated an enhanced decrease in nitrite production and Nos mRNA levels using BDNF-SLNs compared to plain BDNF as a control, validating the proficiency of the microfluidic-based drug delivery systems as pioneering and valuable approaches for the brain delivery of biologicals.

The effects of hyperbaric oxygen therapy on neuroprotection and recovery after brain resuscitation

Objective Analyze the impact of hyperbaric oxygen therapy on neuroprotection and recovery post severe traumatic brain injury (sTBI) resuscitation. Methods Retrospective analysis of clinical data from 83 sTBI patients admitted between January 2022 to January 2024. Patients were divided into control (n = 41) and observation (n = 42) groups based on treatment received. Control received standard therapy, while the observation group received hyperbaric oxygen therapy. Effects on clinical outcomes, neuroinjury markers (S100β, GFAP, UCH-L1, NSE), neurotrophic factors (NGF, BDNF), neurological function indicators (NIHSS, CSS), and adverse reactions were compared. Results The observation group showed a higher total effective rate (80.95%) compared to control (60.98%) (p < 0.05). Neuroinjury markers decreased post-treatment in both groups, with the observation group lower (p < 0.05). NGF and BDNF levels increased post-treatment in both groups, with the observation group higher (p < 0.05). NIHSS and CSS scores decreased post-treatment in both groups, with the observation group lower (p < 0.05). No significant difference in adverse reactions between groups (p > 0.05). Conclusion Hyperbaric oxygen therapy effectively treats sTBI by improving brain resuscitation success, reducing neuroinjury factors, enhancing neurotrophic factors, and promoting neurological function recovery, without increasing adverse reaction risk.

Activation of Wnt signaling mitigates blood-brain barrier disruption by inhibiting vesicular transcytosis after traumatic brain injury in mice

Elevated transport of Caveolin-1 (CAV-1) vesicles within vascular endothelial cells constitutes a significant secondary pathogenic event contributing to the compromise of the blood-brain barrier (BBB) post-traumatic brain injury (TBI). While Wnt/β-catenin signaling is recognized for its critical involvement in angiogenesis and the maintenance of BBB integrity, its influence on vascular endothelial transcytosis in the aftermath of TBI is not well-defined. This study aims to elucidate the impact of Wnt/β-catenin signaling on cerebrovascular vesicular transcytosis following TBI. In this experiment, adult male wild-type (WT) C57BL/6 mice underwent various interventions. TBI was induced utilizing the controlled cortical impact technique. Post-TBI, mice were administered either an inhibitor or an agonist of Wnt signaling via intraperitoneal injection. Recombinant adeno-associated virus (rAAV) was administered intracerebroventricularly to modulate the expression of the CAV-1 inhibitory protein, Major facilitator superfamily domain-containing 2a (Mfsd2a). This research utilized Evans blue assay, Western blot analysis, immunofluorescence, transmission electron microscopy, and neurobehavioral assessments. Post-TBI observations revealed substantial increases in macromolecule (Evans blue and albumin) leakage, CAV-1 transport vesicle count, astrocyte end-feet edema, and augmented aquaporin-4 (AQP4) expression, culminating in BBB disruption. The findings indicate that Wnt signaling pathway inhibition escalates CAV-1 transport vesicle activity and aggravates BBB compromise. Conversely, activating this pathway could alleviate BBB damage by curtailing CAV-1 vesicle presence. Post-TBI, there is a diminution in Mfsd2a expression, which is directly influenced by the modulation of WNT signals. Employing a viral approach to regulate Mfsd2a, we established that its down-regulation undermines the protective benefits derived from reducing CAV-1 transport vesicles through WNT signal enhancement. Moreover, we verified that the WNT signaling agonist LiCl notably ameliorates neurological deficits following TBI in mice. Collectively, our data imply that Wnt/β-catenin signaling presents a potential therapeutic target for safeguarding against BBB damage and enhancing neurological function after TBI.

Metabolic Diaschisis in Mild Traumatic Brain Injury.

Neurophysiological diaschisis presents in traumatic brain injury (TBI) as functional impairment distant to the lesion site caused by axonal neuroexcitation and deafferentation. Diaschisis studies in TBI models have evaluated acute phase functional and microstructural changes. Here, in vivo biochemical changes and cerebral blood flow (CBF) dynamics following TBI are studied with magnetic resonance. Behavioral assessments, magnetic resonance spectroscopy (MRS), and CBF measurements on rats followed cortical impact TBI. Data were acquired pre-TBI and 1-3 h, 2-days, 7-days, and 14-days post-TBI. MRS was performed on the ipsilateral and contralateral sides in the cortex, striatum, and thalamus. Metabolites measured by MRS included N-acetyl aspartate (NAA), aspartate (Asp), lactate (Lac), glutathione (GSH), and glutamate (Glu). Lesion volume expanded for 2 days post-TBI and then decreased. Ipsilateral CBF dropped acutely versus baseline on both sides (-62% ipsilateral, -48% contralateral, p < 0.05) but then recovered in cortex, with similar changes in ipsilateral striatum. Metabolic changes versus baseline included increased Asp (+640% by Day 7 post-TBI, p < 0.05) and Lac (+140% on Day 2 post-TBI, p < 0.05) in ipsilateral cortex, while GSH (-67% acutely, p < 0.05) and NAA decreased (-50% on Day 2, p < 0.05). In contralateral cortex Lac decreased (-73% acutely, p < 0.05). Analysis of variance showed significance for Side (p < 0.05), Time after TBI (p < 0.05), and interactions (p < 0.005) for Asp, GSH, Lac, and NAA. Transient decreases of GSH (-30%, p < 0.05, acutely) and NAA (-23% on Day 2, p < 0.05) occurred in ipsilateral striatum with reduced GSH (-42%, p < 0.005, acutely) in the contralateral striatum. GSH was decreased in ipsilateral thalamus (-59% ipsilateral on Day 2, p < 0.05). Delayed increases of total choline were seen in the contralateral thalamus were noted as well (+21% on Day 7 post-TBI, p < 0.05). Both CBF and neurometabolite concentration changes occurred remotely from the TBI site, both ipsilaterally and contralaterally. Decreased Lac levels on the contralateral cortex following TBI may be indicative of reduced anaerobic metabolism during the acute phase. The timing and locations of the changes suggest excitatory and inhibitory signaling processes are affecting post-TBI metabolic fluctuations.

Hypidone hydrochloride (YL-0919) ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation.

JOURNAL/nrgr/04.03/01300535-202508000-00023/figure1/v/2024-09-30T120553Z/r/image-tiff Traumatic brain injury involves complex pathophysiological mechanisms, among which oxidative stress significantly contributes to the occurrence of secondary injury. In this study, we evaluated hypidone hydrochloride (YL-0919), a self-developed antidepressant with selective sigma-1 receptor agonist properties, and its associated mechanisms and targets in traumatic brain injury. Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema. Next, we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells. Finally, the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist (BD-1047). Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury, while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema. Furthermore, YL-0919 effectively combated oxidative stress both in vivo and in vitro. The protective effects of YL-0919 were partially inhibited by BD-1047. These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress, a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047. YL-0919 may have potential as a new treatment for traumatic brain injury.

Reliability in distinguishing murder from accidental event with current forensic criteria in traumatic head injury

Discovering a body displaying signs of multiple head trauma requires a thorough examination by the forensic pathologist, and a multidisciplinary approach is recommended. However, determining the manner of death is not always possible. We present a case in which the body of a 60-year-old man was discovered lying face down on the floor of his apartment, partially unclothed, surrounded by blood and vomit, and presenting numerous head injuries. The autopsy concluded that the cause of death was a result of post-traumatic brain injury. Nevertheless, applying current criteria made it challenging to ascertain whether the trauma stemmed from an accidental event or an assault.

Single Nucleotide Polymorphism in Cell Adhesion Molecule L1 Affects Learning and Memory in a Mouse Model of Traumatic Brain Injury.

The L1 cell adhesion molecule (L1) has demonstrated a range of beneficial effects in animal models of spinal cord injury, neurodegenerative disease, and ischemia; however, the role of L1 in TBI has not been fully examined. Mutations in the L1 gene affecting the extracellular domain of this type 1 transmembrane glycoprotein have been identified in patients with L1 syndrome. These patients suffer from hydrocephalus, MASA (mental retardation, adducted thumbs, shuffling gait, aphasia) symptoms, and corpus callosum agenesis. Clinicians have observed that recovery post-traumatic brain injury (TBI) varies among the population. This variability may be explained by the genetic differences present in the general population. In this study, we utilized a novel mouse model of L1 syndrome with a mutation at aspartic acid position 201 in the extracellular domain of L1 (L1-201). We assessed the impact of this specific single nucleotide polymorphism (SNP) localized to the X-chromosome L1 gene on recovery outcomes following TBI by comparing the L1-201 mouse mutants with their wild-type littermates. We demonstrate that male L1-201 mice exhibit significantly worse learning and memory outcomes in the Morris water maze after lateral fluid percussion (LFP) injury compared to male wild-type mice and a trend to worse motor function on the rotarod. However, no significant changes were observed in markers for inflammatory responses or apoptosis after TBI.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60mg/kg). At 48h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia NeurologicalTest scores and animal weight changes at 24h and 48h after injury. I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24h and 48h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I +TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Increasing Risk of Dementia Among Patients with Subsequent Epilepsy Within 2 Years Post-Traumatic Brain Injury: A Population-Based Case-Control Study.

Although the association between neurodegenerative diseases, such as dementia, and traumatic brain injury (TBI) has long been known, the association between dementia and TBI with epilepsy has been controversial. This data-driven population-based study is designed to investigate the association between dementia and epilepsy after TBI within a 2-year period. This case-control cohort study was conducted using the Longitudinal Health Insurance Database 2000 (LHID2000). We included 784 individuals ambulatory or hospitalized for TBI with epilepsy from 2001 to 2011, compared with 2992 patients with TBI without epilepsy who were matched for characteristics including sex, age, and healthcare resource use index date. Every participant was followed up for 5 years to ascertain any dementia development. Data were stratified and analyzed using the Cox proportional hazards regression. Through the 5-year follow-up period, 39 patients (5.21%) with TBI with epilepsy and 55 (1.53%) with TBI without epilepsy developed dementia. TBI with epilepsy was independently associated with a >3.03 times risk of dementia after correcting for age, sex, and comorbidities. These findings suggest an increased risk of dementia in patients with TBI with epilepsy. Our research recommends that individuals with TBI and epilepsy be monitored more intensively.

Profiles of executive functioning following traumatic brain injury and stroke using the assessment of participation and executive functions: combined cross-sectional and longitudinal designs.

The Assessment of Participation and Executive Functions (A-PEX) evaluates executive functioning through daily participation in complex daily activities. This study examines its ability to discriminate between executive functioning profiles post-traumatic brain injury and post-stroke and its sensitivity to changes. Cross-sectional with a longitudinal component. Adults with post-traumatic brain injury (n = 28) and post-stroke (n = 26) in a rehabilitation facility. Patients were administered the A-PEX, Multiple Errands Test-Hospital version and Color Trail Test at 2 time-points 1 month apart. The Montreal Cognitive Assessment was administered at the first time-point, and Executive Functions Performance Test's Internet-based Bill Payment subtest at the second. The analysis used Mann-Whitney and Wilcoxon signed-rank tests. The stroke group's A-PEX scores were higher than the traumatic brain injury group's at the first time-point (p < 0.05). No differences were found in the other assessments. Within-group differences in both groups were significant in the A-PEX (-3.7 < r < - 2.3, p < 0.05) and Multiple Errands Test-Hospital version (-3.4 < r < -3.3, p < 0.01). The A-PEX may provide valuable information about the uniqueness of executive functioning profiles and patients' progress.

CHANGES IN FUNCTIONAL CONNECTIVITY FOLLOWING INTENSIVE ATTENTION TRAINING IN PATIENTS WITH TRAUMATIC BRAIN INJURY. A PILOT STUDY.

To explore functional connectivity after intensive attention training in the chronic phase after traumatic brain injury as clinical evidence indicates that intensive attention training improves attention dysfunction in persons with traumatic brain injury. A case series study. Two young adults, 13- and 18-months post traumatic brain injury, with traumatic brain injury induced attention deficits were assigned to 20 h of intensive attention training and neuroimaging. Functional magnetic resonance imaging during a psychomotor vigilance test was conducted pre- and post-intervention. The neuroimaging indicated both increased and decreased connectivity density in frontal, posterior and subcortical brain regions, for some regions with separate change patterns for left and right hemisphere respectively, and an overall reduction in variability in functional connectivity. The changed and decreased variability of functional connectivity in various brain regions, captured by fMRI during a psychomotor vigilance test after direct attention training in a small sample of persons with traumatic brain injury, suggests further studies of functional connectivity changes in neural networks.

Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages.

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country's healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI. Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis. Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI. The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.

Neural Plasticity after Traumatic Brain Injuries. Importance of neurological rehabilitation

The research aimed to deepen the understanding of the role of neuroplasticity in post-traumatic injuries that cause physical damage to neuronal tissue. The study focused on how the brain, through epigenetic remodeling, adapts and responds to these initial injuries to facilitate recovery. The methodology included a descriptive bibliographic review, limited to articles in English and Spanish published between 2019 and 2023, using databases such as Clinical Key, PubMed, Scopus, Science Direct, Web of Science, and Google Scholar. Relevant scientific articles, books, and recognized guides were included. Additionally, five clinical cases of patients with traumatic brain injury were evaluated through a review of medical histories and interviews with the medical care team to analyze the effectiveness of neurorehabilitation. The results highlighted that neuronal plasticity, the ability of the nervous system to adapt and reorganize, is fundamental for recovery after a traumatic brain injury. It was observed that neuroplasticity processes, both structural and functional, allow the formation of new synapses and the strengthening of existing ones, facilitating the recovery of motor and cognitive functions. Neurorehabilitation, which includes techniques such as physical therapy, occupational therapy, speech therapy, and neurostimulation, proved effective in improving the quality of life of patients. The research concluded by emphasizing the importance of neuroplasticity and neurorehabilitation in the recovery of patients with post-traumatic brain injuries, recommending the implementation of individualized and advanced therapeutic approaches to optimize outcomes

Post-traumatic Cerebral Infarction: A Severe form of Secondary Brain Injury in Traumatic Brain Injury Patients with a Critical Neutrophil-to-lymphocyte Ratio

Post-traumatic cerebral infarction (PTCI) is one of the most severe forms of secondary brain injury (SBI) post-traumatic brain injury (TBI). The PTCI incidence is not very often and is associated with a high mortality rate even after appropriate medical and surgical interventions. SBI is still challenging to prevent even though several laboratory tests such as neutrophil-to-lymphocyte ratio (NLR) were available for early detection and monitoring the severity of SBI progression. This study aimed to report the case of PTCI post-TBI which was correlated with an extremely high NLR result. This case report shows that early recognition and close monitoring is necessary to prevent the occurrence of PTCI in TBI patients. NLR is very beneficial to be used to monitor and detect the early progression of SBI post-TBI.

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury.

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

SOCIAL INTEGRATION, COGNITION, AND FUNCTIONAL OUTCOME IN OLDER ADULTS FOLLOWING TRAUMATIC BRAIN INJURY

Abstract Persons aged 65 and older have the highest rates of traumatic brain injury (TBI), and this injury is known to be related to significant, persistent functional changes. What is not known is what factors may mediate these changes. The current study aimed 1) to examine interrelationships among social integration, functional outcome, and cognition in older adults at years 1, 2, and 5 post-traumatic brain injury (TBI) and 2) to examine if functional outcome mediates the concurrent and longitudinal relationships between social integration and cognitive function post-TBI in older adults. This is a secondary analysis of data obtained from Traumatic Brain Injury Model System National Database (TBIMS-NDB). Included subjects from the database were persons aged 65 years and older at the time of injury (N=1469). We used longitudinal mediation analysis to address study aims. We found that social integration had a direct effect on functional outcome and cognition at 1, 2, and 5-years post-TBI. Functional outcome had a positive direct effect on concurrent cognitive function. Regarding mediation, social integration and cognition were mediated by concurrent functional outcome. However, there were no significant mediating effects of concurrent functional outcome on concurrent social integration or subsequent cognitive function. Our findings suggest there are positive relationships between social integration, functional outcome, and cognition over time. With a better understanding of these interrelationships, tailored interventions that target social integration, such as activities fostering a sense of belonging in the community and cultural diversity programs may promote improved functional and cognitive outcomes.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models.

Traumatic brain injury is a major cause of death and disability worldwide, affecting over 69 million individuals yearly. One-carbon metabolism has been shown to have beneficial effects after brain damage, such as ischemic stroke. However, whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation. The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury. PubMed, Web of Science, and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes. The search terms included combinations of the following words: traumatic brain injury, dietary supplementation, one-carbon metabolism, and B-vitamins. The focus of each literature search was basic science data. The year of publication in the literature searches was not limited. Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recovery of animals with traumatic brain injury compared to controls. However, this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delivery of vitamin supplementation post-traumatic brain injury. The details of supplementation post-traumatic brain injury need to be further investigated. Overall, we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems. Further investigation in a clinical setting should be strongly considered in conjunction with current medical treatments for traumatic brain injury-affected individuals.

Syndrome of the Trephined, a Rare Complication of Decompression Craniotomy: A Case Report

Post-traumatic brain injury can lead to intracranial hypertension, which is a serious neurological emergency that may require decompressive craniotomy (DC). However, decompressive craniotomies can give rise to complications in some patients during their recovery phase, in particular the "trephine" syndrome, which adversely affects patients' functional rehabilitation. The main symptoms are severe orthostatic headaches, motor deficits, cognitive decline and convulsions. Imaging, particularly CT scans, is essential for making a positive diagnosis and monitoring patient progress. In this study, we describe a case of skin flap syndrome secondary to post-traumatic decompression.

MRI Markers for Detecting Accelerated Alzheimer’s Disease after Neurotrauma

AbstractBackgroundA history of traumatic brain injury (TBI) is linked to an earlier onset of Alzheimer’s disease (AD) (Nemetz et al., 1999). Evidence showed that the more severe the injury, the greater risk of developing AD (Johnson et al.,2010). However, systematic evaluation of in vivo MRI markers in the monitoring of AD progression after trauma is lacking. Here, we investigated the performance of various MRI markers in tracking AD progression after neurotrauma in a mouse model of AD. The following MRI sequences were investigated: dynamic contrast‐enhanced (DCE) MRI, Fluid attenuated inversion recovery (FLAIR) MRI, Quantitative Susceptibility Mapping (QSM) and diffusion MRI.Method3xTg‐AD mice (Jackson Laboratory, ME) were bred and maintained at Boston University. Unanesthetized mice were pretreated with a non‐sedating dose of the analgesic buprenorphine (0.2mg/kg, i.p.) prior to TBI. Male and female 3xTg‐AD mice were subjected to left‐lateral closed‐head impact injury at 10‐12 weeks of age as described in our previous work (Tagge et al., 2018). MRI data were acquired at 1 day, 3 days, 1 month and 3 months post TBI. DCE‐MRI was analyzed using in‐house software programmed in Matlab (Mathworks, MA). The volume of white matter hyperintensity was measured using manual contours in ImageJ (NIH). QSM data was analyzed using JHU/KKI QSM Toolbox (Li et al, 2019). Diffusion MRS was analyzed in DSI Studio (http://dsistudio.labsolver.org). Age, gender matched 3xTg‐AD mice without TBI were used as controls.ResultIncreased blood‐brain permeability was detected by DCE‐MRI and changes of white matter susceptibility detected by QSM were observed in the subacute phase (1‐3 days) post TBI. Accelerated development of white matter hyperintensity was observed as early as 1 month post TBI.ConclusionMRI markers provide valuable measures of the integrities of blood‐brain barrier and white matter after neurotrauma in vivo, and have the potential to facilitate the management of neurotrauma subjects with a risk of accelerated AD development.

Neurotrophins and neural stem cells in posttraumatic brain injury repair.

Traumatic brain injury (TBI) is the main cause of disability, mental health disorder, and even death, with its incidence and social costs rising steadily. Although different treatment strategies have been developed and tested to mitigate neurological decline, a definitive cure for these conditions remains elusive. Studies have revealed that various neurotrophins represented by the brain-derived neurotrophic factor are the key regulators of neuroinflammation, apoptosis, blood-brain barrier permeability, neurite regeneration, and memory function. These factors are instrumental in alleviating neuroinflammation and promoting neuroregeneration. In addition, neural stem cells (NSC) contribute to nerve repair through inherent neuroprotective and immunomodulatory properties, the release of neurotrophins, the activation of endogenous NSCs, and intercellular signaling. Notably, innovative research proposals are emerging to combine BDNF and NSCs, enabling them to synergistically complement and promote each other in facilitating injury repair and improving neuron differentiation after TBI. In this review, we summarize the mechanism of neurotrophins in promoting neurogenesis and restoring neural function after TBI, comprehensively explore the potential therapeutic effects of various neurotrophins in basic research on TBI, and investigate their interaction with NSCs. This endeavor aims to provide a valuable insight into the clinical treatment and transformation of neurotrophins in TBI, thereby promoting the progress of TBI therapeutics.