Search

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of excessive sympathetic activity, mainly occurring in severe traumatic brain injury. However, few studies have reported the frequency of PSH and its related risk factors in adult patients with brain injury.We performed this systematic review and meta-analysis to estimate the combined incidence of PSH and the associated risk factors in adult patients with brain injury. This study was registered with the PROSPERO international prospective register of systematic reviews (https://www.crd.york. ac.uk/PROSPERO/Identifier: CRD 42021260493), and a systematic search was conducted of the scientific databases Embase, PubMed, Web of Science, Cochrane Library, and Google Scholar. All identified observational studies regarding the incidence and risk factors of PSH in adult patients with brain injury were included. Two authors extracted data independently; data were analyzed by STATA version 16.The search yielded 9 studies involving 1643 adult patients. PSH was detected in 438 patients. The combined incidence of PSH in adult patients with brain injury was 27.4% (95% confidence interval [CI], 0.190-0.358). The risk factors include patients' age (SMD = -0.592; IPSH occurs in nearly a quarter of adult patients with brain injury. Patient's age, traffic accident, admission Glasgow Coma Scale score, hydrocephalus, and diffuse axonal injury were risk factors for PSH in adult patients with brain injury. These findings may contribute to novel strategies for early diagnosis and interventions that aid in the rehabilitation of patients with brain injury.

Rationale and Objectives Recently, advanced magnetic resonance imaging has been widely adopted to investigate altered structure and functional activities in patients with diffuse axonal injury (DAI), this patient presumed to be caused by shearing forces and results in significant neurological effects. However, little is known regarding cerebral temporal dynamics and its predictive ability in the clinical dysfunction of DAI. Materials and Methods In this study, static and dynamic fractional amplitude of low-frequency fluctuation (fALFF), an improved approach to detect the intensity of intrinsic neural activities, and their temporal variability were applied to examine the alteration between DAI patients (n = 24) and healthy controls (n = 26) at the voxel level. Then, the altered functional index was used to explore the clinical relationship and predict dysfunction in DAI patients. Results We discovered that, compared to healthy controls, DAI patients showed commonly altered regions of static fALFF, and its variability was mainly located in the left cerebellum posterior lobe. Furthermore, decreased static fALFF values over the left cerebellum posterior lobe and bilateral medial frontal gyrus showed significant correlations with disease duration and Mini-Mental State Examination scores. More important, the increased temporal variability of dynamic fALFF in the left caudate could predict the severity of the Glasgow Coma Scale score in DAI patients. Conclusion Overall, these results suggested selective abnormalities in intrinsic neural activities with reduced intensity and increased variability, and this novel predictive marker may be developed as a useful indicator for future connectomics or artificial intelligence analyses.

Traumatic hemorrhage of the bilateral basal ganglia is an extremely rare event in severe closed head injuries. Its mechanism remains poorly understood. This report describes the rare case of bilateral traumatic basal ganglia hemorrhage in a 33-year-old man, who had been a victim of violent head trauma. Magnetic resonance imaging and serial computed tomography revealed small hemorrhages in the bilateral basal ganglia as well as nonhemorrhagic diffuse axonal injury in the bilateral internal capsules. The patient was discharged without neurologic deficits following conservative management. Overall, this case report highlights that shearing injury is a potential cause of bilateral traumatic basal ganglia hemorrhage.

Background Traumatic brain injury (TBI) is characterized by high prevalence, morbidity, and mortality. Diffuse axonal injury (DAI) is a specific type of TBI leading to prolonged consciousness impairment and disability. There is still no standard treatment for DAI, so we introduced traditional Chinese medicine into the treatment of these patients. Case summaries Three patients had TBI after traffic accidents. Their Glasgow Coma Scale (GCS) scores in the intensive care unit (ICU) were E1VEM2-3, E1VEM2-3, and E1VEM2 respectively. All of them were diagnosed with DAI based on magnetic resonance imaging (MRI). Because of continuing consciousness disturbances, their families agreed to combine traditional Chinese medicine and modern medicine treatments through inpatient consultation in Taoyuan General hospital. Two patients took Buyang Huanwu Decoction, and one Tianma Gouteng Decoction twice a day. All of them received 20 min of acupuncture treatments 5 times per week. Acupuncture points included Baihui (GV20), Sishencong (EX-HN1), Shuigou (GV26), Hegu (LI4), and Taichong (LR3). All of them started Traditional Chinese medicine treatment within 2 weeks after TBI. The GCS of all three patients recovered to E4M5V6. Conclusions The early addition of traditional Chinese medicine treatments to Western medical care can improve the prognosis of patients with diffuse axonal injury., Graphical abstract Image 1, Highlights • Traumatic brain injury diagnosed with diffuse axonal injury, the lower GCS, the poorer outcome. This article points out that combining Chinese medicine and modern medicine can lead to better outcome(motor, speech function and GCS score). • Chinese medicine has neuroprotective effect and it’s safe when combining with modern medicine in severe traumatic brain injury in this cases report.

Objectives: Preclinical studies have shown that surgically implanted vagus nerve stimulation (VNS) promotes recovery of consciousness and cognitive function following experimental traumatic brain injury (TBI). The aim of this study is to report the feasibility and safety of a noninvasive transcutaneous vagus nerve stimulation (tVNS) in patients with persistent impairment of consciousness following severe TBI. Materials and Methods: The feasibility of tVNS was evaluated in five patients presenting with diffuse axonal injury and reduced dominant EEG activity one month following severe TBI. tVNS was applied to the left cymba conchae of the external ear using a skin electrode four hours daily for eight weeks. Possible effects of tVNS on physiological parameters and general side effects were recorded. In addition, we report the rate of recovery using coma recovery scale revised (CRS-R). Results: The tVNS regime of four hours daily for eight weeks was feasible and well tolerated with little side effects and no clinically relevant effects on physiological parameters. Three patients showed improvements (>3 points) in the CRS-R following eight weeks tVNS. Conclusion: We demonstrated that tVNS is a feasible and safe VNS strategy for patients following severe TBI. Controlled studies are needed to clarify whether tVNS has a potential to promote recovery of consciousness following severe TBI.

Diffuse axonal injury (DAI) is one of the most common and severe pathological consequences of traumatic brain injury (TBI). The molecular mechanism of DAI is highly complicated and still elusive, yet a clear understanding is crucial for the diagnosis, treatment, and prognosis of DAI. In our study, we used rats to establish a DAI model and applied isobaric tags for relative and absolute quantitation (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins (DEPs) in the corpus callosum. As a result, a total of 514 proteins showed differential expression between the injury groups and the control. Among these DEPs, 14 common DEPs were present at all seven time points postinjury (1, 3, 6, 12, 24, 48, and 72 h). Next, bioinformatic analysis was performed to elucidate the pathogenesis of DAI, which was found to possibly involve calcium ion-regulatory proteins (e.g., calsenilin and ryanodine receptor 2), cytoskeleton organization (e.g., peripherin, NFL, NFM, and NFH), apoptotic processes (e.g., calsenilin and protein kinase C delta type), and inflammatory response proteins (e.g., complement C3 and C-reactive protein). Moreover, peripherin and calsenilin were successfully confirmed by western blotting to be significantly upregulated during DAI, and immunohistochemical (IHC) analysis revealed that their expression increased and could be observed in axons after injury, thus indicating their potential as DAI biomarkers. Our experiments not only provide insight into the molecular mechanisms of axonal injury in rats during DAI but also give clinicians and pathologists important reference data for the diagnosis of DAI. Our findings may expand the list of DAI biomarkers and improve the postmortem diagnostic rate of DAI.

Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairment in impulsive choice. Histological analyses revealed reduced dopaminergic innervation from the ventral tegmental area to the olfactory tubercle, consistent with altered impulsivity neurocircuitry. Consistent with diffuse axonal injury generated by CHIMERA, white matter inflammation, tau immunoreactivity and degeneration were observed in the optic tract and corpus callosum. Finally, pronounced grey matter microgliosis was observed in the olfactory tubercle. Our results provide insight into the mechanisms by which rTBI leads to post-traumatic psychiatric-like symptoms in a novel rat TBI platform.

Highlights • We report a case of WEMINO caused by mild traumatic brain injury, presenting with typical left ocular manifestations. • CT scan of brain was noncontributory, but MRI managed to delineate the site of injury in the MLF in the left temporo-occipital white matter. • Although more common in demyelinating diseases, clinicians should be cognizant of this syndrome in mild TBI patients that have ocular exotropia., Introduction Walled-eyed monocular internuclear ophthalmoplegia (WEMINO) syndrome is a sub-variant of internuclear ophthalmoplegia (INO) and involves the same clinical findings with the addition of exotropia of the ipsilateral eye. Causes typically include multiple sclerosis (MS) and ischemia (hemorrhagic or embolic) but can be secondary to blunt trauma as seen in our presented case. Presentation of case A 27-year-old man presented with new-onset visual changes, diplopia, and strabismus following a motor vehicle collision. Physical exam showed left ocular exotropia and slight hypertropia on forward gaze with deficiency of left convergence and disconjugate eye movements on horizontal gaze with right nystagmus on rightward gaze. Imaging showed hyperintensities in the right middle cerebellar peduncle and left temporal-occipital white matter likely consistent with diffuse axonal injury but otherwise nonspecific. The patient was treated conservatively with left eyepatch and exhibited improvement of exotropia and diplopia at 1 week follow up. Discussion Common causes of WEMINO syndrome include MS and ischemia with no prior reports, to our knowledge, being secondary to the blunt trauma seen in our case. Patients with WEMINO present with the typical signs of failure of ipsilateral adductive movement during lateral along with ipsilateral exotropia. Management involves treating the underlying disorder, if possible, with conservative measures with traumatic origins. Conclusion Until now, WEMINO syndrome secondary to trauma has not been previously documented. Our patient was effectively treated with conservative measures alone.

Background Traumatic brain injury (TBI) is the major public health problem worldwide, particularly in the Middle East. Diffuse axonal injury (DAI) is commonly found in TBI. Although DAI can lead to physical and psychosocial disabilities, its prognostic value is still a matter of debate. Magnetic Resonance (MR) is more sensitive for detecting DAI lesions. Objective To identify the radiological and clinical factors associated with the functional capacity one year after the traumatic brain injury. Methods The study included 251 patients with severe head trauma for whom Brain MRI was done within one month after injury. Demographic, clinical, and radiological data were collected during hospitalization. Neurocognitive and psychiatric evaluation were done one year thereafter. Results DAI was more frequent in our patients. Psychiatric disorders, cognitive impairment, and poor functional outcome were more common in patients with DAI especially those with cerebral hemisphere and brain stem lesion, and mixed lesions. Duration of post traumatic amnesia (DPTA), lost consciousness and hospital stay (DHS) as well as the volume of diffuse axonal injury (DAI) were associated with poor neurocognitive outcome. DPTA, and DAIV may be considered independent factors that could predict the neurocognitive outcome. Conclusion MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with poor long-term neurocognitive and psychiatric outcomes.

Double pulsed-field gradient (dPFG) MRI is proposed as a new sensitive tool to detect and characterize tissue microstructure following diffuse axonal injury. In this study dPFG MRI was used to estimate apparent mean axon diameter in a diffuse axonal injury animal model and in healthy fixed mouse brain. Histological analysis was used to verify the presence of the injury detected by MRI.

The pathophysiology associated with mild traumatic brain injury (mTBI) includes neurometabolic and cytoskeletal changes that have been shown to impair structural and functional connectivity. Evidence that persistent neuropsychological impairments post injury are linked to structural and functional connectivity changes is increasing. However, to date the relationship between connectivity changes, heterogeneity of persistent symptoms and recovery post mTBI has been poorly characterised. Recent innovations in neuroimaging provide new ways of exploring connectivity changes post mTBI. Namely, combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) offers several advantages over traditional approaches for studying connectivity changes post TBI. Its ability to perturb neural function in a controlled manner allows for measurement of causal interactions or effective connectivity between brain regions. We review the current literature assessing structural and functional connectivity following mTBI and outline the rationale for the use of TMS-EEG as an ideal tool for investigating the neural substrates of connectivity dysfunction and reorganisation post mTBI. The diagnostic, prognostic and potential therapeutic implications will also be explored.

Unconsciousness may be due to severe brain damage or to potentially reversible causes. Noncontrast head computed tomography (CT) helps identify acute ischemic and hemorrhagic lesions as well as certain patterns of toxic encephalopathy. MR imaging plays an important role in the assessment of acutely encephalopathic patients who may show no significant abnormality on CT. This review describes some of the common and infrequent entities that can lead to unconsciousness, including epilepsy and vascular, traumatic, metabolic, and toxic disorders.

Diffuse axonal injury (DAI) is much common during traumatic brain injury (TBI) and is associated with high mortality and poor neurological outcome. Although many studies have been examined, there are still no reliable objective diagnostic modalities available for clinicians to make an early diagnosis of DAI. Therefore, we established a rat model of DAI, applying an integrated 1H NMR- and UPLC-Q-TOF/MS-based metabonomics approach to identify differentially changed metabolites in plasma. A total of twenty-two metabolites in the injury group were identified as differentially changed. Among them, four metabolites, glutamine, pyruvate, glycerol and phosphocholine, were identified as candidate biomarkers based on their high fold-changes and biological functions, and may play important roles in axonal injury progression in DAI. Our study not only identified several novel biomarkers that improved our understanding of the metabolic events underlying DAI, but also may provide some potential novel therapeutic targets for preventing axonal injury in DAI.

Neurobasal®/B27 is a gold standard culture media used to study primary neurons in vitro. An alternative media (BrainPhys®/SM1) was recently developed which robustly enhances neuronal activity vs. Neurobasal® or DMEM. To the best of our knowledge BrainPhys® has not been explored in the setting of neuronal injury. Here we characterized the utility of BrainPhys® in a model of in vitro mechanical-stretch injury. Methods/results Primary rat cortical neurons were maintained in classic Neurobasal®, or sequentially maintained in Neurocult® followed by BrainPhys® (hereafter simply referred to as “BrainPhys® maintained neurons”). The levels of axonal markers and proteins involved in neurotransmission were compared on day in vitro 10 (DIV10). BrainPhys® maintained neurons had higher levels of GluN2B, GluR1, Neurofilament light/heavy chain (NF-L & NF-H), and protein phosphatase 2 A (PP2A) vs. neurons in Neurobasal®. Mechanical stretch-injury (50 ms/54% biaxial stretch) to BrainPhys® maintained neurons modestly (albeit significantly) increased 24 h lactate dehydrogenase (LDH) levels but markedly decreased axonal NF-L levels post-injury vs. uninjured controls or neurons given a milder 38% stretch-injury. Furthermore, two 54% stretch-injuries (in tandem) exacerbated 24 h LDH release, increased α-spectrin breakdown products (SBDPs), and decreased Tau levels. Also, BrainPhys® maintained cultures had decreased markers of cell damage 24 h after a single 54% stretch-injury vs. neurons in Neurobasal®. Finally, we tested the hypothesis that lentivirus mediated overexpression of the pro-death protein RBM5 exacerbates neuronal and/or axonal injury in primary CNS cultures. RBM5 overexpression vs. empty-vector controls increased 24 h LDH release, and SBDP levels, after a single 54% stretch-injury but did not affect NF-L levels or Tau. Conclusion BrainPhys® is a promising new reagent which facilities the investigation of molecular targets involved in axonal and/or neuronal injury in vitro.

Traumatic axonal injury (TAI) is a distinct clinicopathological entity that can cause serious impairment of the brain function and can sometimes be found as a concrete cause of death. It has been discussed from the perspective of its biomechanical importance, and also from the standpoint of certain criteria for the pathological diagnosis of TAI. However, since the time when DAI (diffuse axonal injury) was initially described, there have been few, if any, discussions about the clinical-pathological correlation in TAI. This paper is an attempt to address this issue. For the purpose of certain pathological diagnoses of TAI, 63 cases with closed head injuries have been subjected to the complete forensic-neuropathological examination, involving immunohistochemistry with antibody against β-APP. In the diagnosis of TAI strict criteria have been followed. Then, retrograde analysis of the clinical parameters has been performed in order to determine some clinical-pathological correlation. The following two most reliable parameters of the impairment of the brain function have been analyzed: the impairment of the consciousness and the time of survival. Comparing the two groups, the one with TAI and the other without TAI, and using appropriate statistical evaluation, our results show that TAI is not a significant contributing factor to the lethal outcome in the early post injury period (24 h), but it is undoubtedly a contributing factor for the severe impairment of the brain function indicated through the status of the consciousness.

Aim The purpose of this study was to document the incidence and pattern of cervical spine (c-spine) injuries in children below 36months with inflicted trauma. Methods An IRB approved, prospective cohort study was performed between July 2011 and January 2016. Inclusion criteria were: age below 36months, loss of consciousness after inflicted trauma, and one initial head computed tomography finding: a subdural, intraventricular, intraparenchymal, subarachnoid hemorrhage, diffuse axonal injury, hypoxic injury, or cerebral edema. A protocol of brain and neck magnetic resonance imaging and angiography was obtained within 48h. Variables were compared by t-test and Fisher-exact test. Results There were 53 children (median age: five months; range: 1–35months), 38 males (71.7%), of which seven died (13.2%). C-spine injury was identified in 8 (15.1%): ligamentous injury (2), vertebral artery shear injury (1), atlantooccipital dissociation (AOD) (1), cord injury with cord epidural hematoma (2), and isolated cord epidural hematoma (2). Retinal hemorrhages (p=0.02), shaking (p=0.04), lower Glasgow coma score (GCS) (p=0.01), brain infarcts (p=0.01), and hypoxic/ischemic injury (p=0.01) were associated with c-spine injury. One with AOD died. Six had significant disability. Conclusion For small children with inflicted trauma, the c-spine injury incidence is 15.1%. The injury pattern includes retinal hemorrhages, shaking, lower GCS, and brain injury. Evaluation of shaken infants should include c-spine imaging. Level of evidence Level 2 A- This is a prospective cohort study with complete follow-up to hospital discharge or death. In all cases, inflicted trauma was confirmed. Owing to the nature of child abuse, the precise time of injury is not known. All children underwent a strict imaging protocol on arrival to hospital that was supervised on a prospective basis.

Chronic traumatic encephalopathy (CTE) is a neuropathologic diagnosis typically made in human brains with a history of repetitive traumatic brain injury (rTBI). It remains unknown whether CTE occurs exclusively after rTBI, or whether a single TBI (sTBI) can cause CTE. Similarly, it is unclear whether impact (eg, motor vehicle accidents) and non-impact (eg, blasts) types of energy transfer trigger divergent or common pathologies. While it is established that a history of rTBI increases the risk of multiple neurodegenerative diseases (eg, dementia, parkinsonism, and CTE), the possible pathophysiologic and molecular mechanisms underlying these risks have yet to be elucidated.

Traumatic brain injury (TBI) is associated with a range of neuropsychological deficits, including attention, memory, and executive functioning attributable to diffuse axonal injury (DAI) with accompanying focal frontal and temporal damage. Although the memory deficit of TBI has been well characterized with laboratory tests, comparatively little research has examined retrograde autobiographical memory (AM) at the chronic phase of TBI, with no prior studies of unselected patients drawn directly from hospital admissions for trauma. Moreover, little is known about the effects of TBI on canonical episodic and non-episodic (e.g., semantic) AM processes. In the present study, we assessed the effects of chronic-phase TBI on AM in patients with focal and DAI spanning the range of TBI severity. Patients and socioeconomic- and age-matched controls were administered the Autobiographical Interview (AI) (Levine, Svoboda, Hay, Winocur, & Moscovitch, 2002) a widely used method for dissociating episodic and semantic elements of AM, along with tests of neuropsychological and functional outcome. Measures of episodic and non-episodic AM were compared with regional brain volumes derived from high-resolution structural magnetic resonance imaging (MRI). Severe TBI (but not mild or moderate TBI) was associated with reduced recall of episodic autobiographical details and increased recall of non-episodic details relative to healthy comparison participants. There were no significant associations between AM performance and neuropsychological or functional outcome measures. Within the full TBI sample, autobiographical episodic memory was associated with reduced volume distributed across temporal, parietal, and prefrontal regions considered to be part of the brain's AM network. These results suggest that TBI-related distributed volume loss affects episodic autobiographical recollection.

Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death. This study investigated the effects of much higher blast-induced accelerations (1200 to 2800G) on neuronal cell death, neuro-inflammation, behavioral deficits and mortality. Adult male rats were subjected to this range of accelerations, in the absence of exposure to blast overpressure, and evaluated over 28days for working memory (Y maze) and anxiety (elevated plus maze). In addition, brains obtained from rats at one and seven days post-injury were used for neuropathology and neurochemical assays. Sixty seven percent of rats died soon after being subjected to blasts resulting in 2800G acceleration. All rats exposed to 2400G acceleration survived and exhibited transient deficits in working memory and long-term anxiety like behaviors, while those exposed to 1200 acceleration G force only demonstrated increased anxiety. Behavioral deficits were associated with acute microglia/macrophage activation, increased hippocampal neuronal death, and reduced levels of tight junction- and synapse- associated proteins. Taken together, these results suggest that exposure of rats to high underbody blast-induced G forces results in neurologic injury accompanied by neuronal apoptosis, neuroinflammation and evidence for neurosynaptic alterations.

The prevalence of neurodegenerative disorders is rapidly increasing. While Alzheimer's disease and dementia generally correlate with longer lifespans, neurodegenerative disorders like chronic traumatic encephalopathy often affect individuals at young age. Historically, the underlying disease mechanisms of these chronic disorders—the slowly changing biochemical composition during aging and the repeated, rapidly changing biomechanical environment during head impact—have been viewed as distinct events. Recent studies suggest that Alzheimer's disease and chronic traumatic encephalopathy share common degenerative pathways on the molecular and cellular levels. Here we examine this current trend and explore the molecular, cellular, tissue, and organ level mechanisms of neurodegeneration through the lens of biomedical engineering. Understanding the underlying disease mechanisms across the spatio-temporal scales of neurodegeneration provides new opportunities to modulate, slow down, and possibly revert molecular dysfunction, axonal death, tissue atrophy, and loss of brain function.

Isolated traumatic oculomotor nerve palsy without internal ophthalmoplegia is a rare condition after closed head trauma. The nerve strain leads to intraneural edema with nerve swelling on T2-weighted magnetic resonance (MR) images and traumatic disruption of the blood peripheral nerve barrier with contrast enhancement on T1-weighted MR images. In this patient, susceptibility-weighted MR imaging allowed the direct visualization of the intraneural hemorrhage after suspected traumatic diffuse neuronal axonal injury.

Background aims Cell therapy in neurological disability after traumatic brain injury (TBI) is in its initial clinical stage. We describe our preliminary clinical experience with three patients with diffuse axonal injury (DAI) who were treated with intrathecal administration of autologous mesenchymal stromal cells (MSCs). Methods Three patients with established neurological sequelae due to DAI received intrathecally autologous MSCs. The total number of MSCs administered was 60 × 10 6 (one patient), 100 × 10 6 (one patient) and 300 × 10 6 (one patient). Results All three patients showed improvement after cell therapy, and subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) showed a diffuse and progressive increase in brain glucose metabolism. Conclusion Our present results suggest benefit of intrathecal administration of MSCs in patients with DAI, as well as a relationship between this type of treatment and increase in brain glucose metabolism. These preliminary findings raise the question of convenience of assessing the potential benefit of intrathecal administration of MSCs for brain diseases in which a decrease in glucose metabolism represents a crucial pathophysiological finding, such as Alzheimer's disease (AD) and other dementias.

This case report reveals the implementation of sensorimotor adaptation and learning process for rehabilitation in a patient with traumatic brain injury to achieve optimum recovery which is permanent in nature in compliance to the disability rating scale. A twenty two year old gentleman who had a history of fall was diagnosed as having subarachnoid hemorrhage along with diffuse axonal injury of the brain and bilateral lung contusion with pneumothorax. He underwent a total of ten months of sensorimotor adaptation and learning process for rehabilitation, which achieved functional mobility with a walker. Keywords: Traumatic brain injury, Rehabilitation, Mobility

Highlights • Neuroendocrine tumor metastasis to the brain is a rare entity that commonly originates from the lungs. • Neuroendocrine tumor grade 1, which is considered benign, can metastasize to the brain. • Neuroendocrine tumor can mimic other cerebral metastatic diseases in terms of hemorrhagic appearance, and thus, should be considered among the differential diagnosis., Background Neuroendocrine tumors (NET) are rare tumors with a low incidence of brain metastasis, especially in grade 1 NET. The most common source of brain metastasis is the lung. We present an unusual case of NET grade 1 with multiple hemorrhagic brain metastases. Case description A 46-year-old woman, who initially presented with a seizure, was diagnosed with multiple brain and lung lesions. She was offered a biopsy for diagnosis, but she refused and lost to follow up. Eighteen years later, she developed progressive quadriparesis and confusion. A biopsy of the left frontal lobe lesions showed NET grade 1. A lung biopsy of the left upper lobe was consistent with the same diagnosis. The patient’s functional status was poor with Eastern Cooperative Oncology Group (ECOG) grade 4. She only received palliative whole-brain radiation therapy (WBRT) and died 3 months after discharge. Clinical discussion NET is a spectrum that encompasses benign to malignant cells. There is a female predominance in lower grades and male predominance in higher grades. No effective management for brain metastases was described, and the prognosis remains poor. Conclusion Multiple brain metastases can be the first presentation of patients with NET. Early diagnosis and treatment may have a more favorable impact on the outcome of this disease. The longstanding numerous hemorrhagic NET brain metastases is exceedingly rare. The neuroimaging appearance is similar to other neoplastic and non-neoplastic lesions. An important differential diagnosis to consider is metastatic melanoma and choriocarcinoma, familial cavernous malformation, diffuse axonal injury, cerebral vasculitis, and amyloid angiopathy.

To identify the relationship between subcallosal haemorrhage and diffuse axonal injury (DAI) grading.Computed tomography (CT) and magnetic resonance imaging (MRI) images of all patients with traumatic brain injury over the past 5 years were reviewed. Subcallosal haemorrhage was defined as the presence of haemorrhage on admission CT underneath the corpus callosum. Grading of DAI was performed using MRI or CT exclusive of subcallosal haemorrhage status. The association of demographic factors, mechanism of injury, Glasgow Coma Scale (GCS) on admission, and positive subcallosal haemorrhage status with the presence of moderate-severe DAI was assessed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of subcallosal haemorrhage status in predicting DAI severity. Median modified Rankin Scale (mRS) scores were compared between subcallosal haemorrhage positive and negative cases.The images of 1,150 patients were reviewed with 301 patients showing DAI. Of those, 64 patients (21.2%) and 237 patients (78.7%) were positive and negative for subcallosal haemorrhage, respectively. Isolated subcallosal haemorrhage was noted in 15 patients (23.4%). A subcallosal haemorrhage positive status (OR=5.16, p 0.001) was statistically significantly associated with moderate-severe DAI. The ROC curve for predicting moderate-severe DAI with subcallosal haemorrhage status showed an area under the curve of 0.625 (95% confidence interval [CI]: 0.561-0.688, p 0.001). The median mRS score was significantly higher (p 0.001) in the subcallosal haemorrhage positive group (median 4.5, interquartile range [IQR] 2-6) versus the negative group (median 2, IQR 2-3). Isolated subcallosal haemorrhage group showed moderate-severe DAI in 80% (12/15) of cases.Subcallosal haemorrhage is a highly specific radiographic predictor of moderate-severe DAI (grade 2-3).

Traumatic brain injury (TBI) is a leading cause of death in the United States. Depending on the severity of injury, complications such as memory loss and emotional changes are common. While the exact mechanisms are still unclear, these cognitive deficiencies are thought to arise from microstructural damages to the brain tissue, such as in diffuse-axonal injury where neuron fibers are sheared. Constitutive models can predict such damage at a microstructural level and allow for insight into the mechanisms of injury initiating at lower length scales. In this study, we developed a continuum damage model of brain tissue that is validated by experimental quasi-static stress-strain tests in tension, compression, and shear. The present work shows that damage is most present in the shear stress state, making the tissue suitable for damage modeling via shear interaction terms. Using this model, new insights into microstructural breakdown due to shear stresses and strains can be gained by application to simulations.

The degree of brain injury is the governing factor for the magnitude of the patient's psycho- and physiological deficits post-injury, and the associated long-term consequences. The present scaling method used to segregate the patients among mild, moderate and severe phases of traumatic brain injury (TBI) has major limitations; however, a more continuous stratification of TBI is still elusive. With the anticipation that differentiating molecular markers could be the backbone of a robust method to triage TBI, we used a modified closed-head injury (CHI) Marmarou model with two impact heights (IH). By definition, IH directly correlates with the impact force causing TBI. In our modified CHI model, the rat skull was fitted with a helmet to permit a diffuse axonal injury. With the frontal cortex as the focal point of injury, the adjacent brain regions (hippocampus, HC and cerebellum, CB) were susceptible to diffuse secondary shock injury. At 8 days post injury (po.i.), rats impacted by 120 cm IH (IH120) took a longer time to find an escape route in the Barnes maze as compared to those impacted by 100 cm IH (IH100). Using a time-resolved interrogation of the transcriptomic landscape of HC and CB tissues, we mined those genes that altered their regulations in correlation with the variable IHs. At 14 days po.i., when all rats demonstrated nearly normal visuomotor performance, the bio-functional analysis suggested an advanced healing mechanism in the HC of IH100 group. In contrast, the HC of IH120 group displayed a delayed healing with evidence of active cell death networks. Combining whole genome rat microarrays with behavioral analysis provided the insight of neuroprotective signals that could be the foundation of the next generation triage for TBI patients.

The physical structure of neurons - dendrites converging on the soma, with an axon conveying activity to distant locations - is uniquely tied to their function. To perform their role, axons need to maintain structural precision in the soft, gelatinous environment of the central nervous system and the dynamic, flexible paths of nerves in the periphery. This requires close mechanical coupling between axons and the surrounding tissue, as well as an elastic, robust axoplasm resistant to pinching and flattening, and capable of sustaining transport despite physical distortion. These mechanical properties arise primarily from the properties of the internal cytoskeleton, coupled to the axonal membrane and the extracellular matrix. In particular, the two large constituents of the internal cytoskeleton, microtubules and neurofilaments, are braced against each other and flexibly interlinked by specialised proteins. Recent evidence suggests that the primary function of neurofilament sidearms is to structure the axoplasm into a linearly organised, elastic gel. This provides support and structure to the contents of axons in peripheral nerves subject to bending, protecting the relatively brittle microtubule bundles and maintaining them as transport conduits. Furthermore, a substantial proportion of axons are myelinated, and this thick jacket of membrane wrappings alters the form, function and internal composition of the axons to which it is applied. Together these structures determine the physical properties and integrity of neural tissue, both under conditions of normal movement, and in response to physical trauma. The effects of traumatic injury are directly dependent on the physical properties of neural tissue, especially axons, and because of axons' extreme structural specialisation, post-traumatic effects are usually characterised by particular modes of axonal damage. The physical realities of axons in neural tissue are integral to both normal function and their response to injury, and require specific consideration in evaluating research models of neurotrauma.

This article provides a concise overview, at the structural and functional level, of those changes evoked by traumatic brain injury across the spectrum of the disease. Using data derived from animals and humans, the pathogenesis of focal versus diffuse brain damage is presented for consideration of its overall implications for morbidity. Emphasis is placed on contusion and its potential expansion in concert with diffuse changes primarily assessed at the axonal level. Concomitant involvement of neuroexcitation and its role in global and focal metabolic changes is considered. Lastly, the influence of premorbid factors including age, genetics, and socioeconomic background is discussed.

TBI is one of the most common causes of hospital admission and a leading cause of death, it is therefore frequently encountered by pathologists in the coronial and medicolegal services. It is not a single entity but a heterogeneous group of pathologies which are caused by different mechanisms and have different survival outcomes and medicolegal implications. TBI is caused by physical contact or acceleration and deceleration mechanisms or a combination of these. It is classified into focal and diffuse damage; both of which should be correlated with the circumstances of death and clinical history before a conclusion can be made regarding their contribution to the cause of death. Focal damage in the brain such as intracranial haemorrhages and contusions can be easily recognised by naked eye examination, but they require detailed description of their anatomical distribution and extent. However the diffuse traumatic brain damage, particularly those related to axonal injury, requires histological and immunohistochemical (IHC) tests to be established. The understanding of the medicolegal implications of focal and diffuse axonal injury has evolved in the last decade with the introduction of better IHC and neuro-radiological methods.

To permit appropriate targeted therapy, the present clinical study was aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eight male DAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1mg/kg per 12h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independence measure (FIM). The markers of inflammation [interleukin-1β (IL-1β), IL-6, transforming growth factor-β1 (TGF-β1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIM scores were observed in progesterone group at the six-month follow-up (P

Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI.

Summary Background Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Preclinical Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. Clinical Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1–4 Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in pre-frontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms.

Traumatic brain injuries (TBIs) induce persistent behavioral and cognitive deficits via diffuse axonal injury. Such axonal injuries are often examined in vivo using diffusion MRI, which identifies demyelinated regions in deep white matter. However, TBI patients can exhibit impairment in the absence of diffusion-measured abnormalities, suggesting that axonal injury and demyelination may occur outside the deep white matter. Importantly, myelinated axons are also present within the cortex. Cortical myelination cannot be measured using diffusion imaging, but can be assessed using the T1/T2 ratio myelin mapping method. Here, we conducted the first work examining effects of TBI on intracortical myelin in living humans by applying the myelin mapping technique to 26 US Military Veterans with varying histories of TBI severity. We observed that myelin maps could be created in individual TBI patients that were similar to known distributions of cortical myelin. Critically, after controlling for participant age, a history of more severe TBI was associated with progressively reduced intracortical myelin in a broad, diffuse pattern across the cortex. Such significant but diffuse reductions in myelin were observed in high-myelin but not low-myelin regions. By contrast, the presence of blast TBI did not affect intracortical myelin above and beyond TBI severity in either a diffuse or focal pattern. These findings suggest that intracortical myelin may be a biomarker of TBI that is anatomically complimentary to diffusion MRI measures of deep white matter. Thus, myelin mapping could potentially be combined with diffusion imaging measures to improve MRI-based diagnostic tools for TBI.

Introduction One of the most common causes of death in Iran and other developing countries, are traffic accidents. Accordingly, this study was done based on the investigation and prevention of traffic injuries. Method This cross sectional study includes all fatal traffic accidents in the province of Kerman during a year; moreover, spss19 software is used for analyzing data. The main references of this survey were both the clinical reports of the victims of the road accidents as well as their Autopsy findings in forensic medicine center of the Iranian province of Kerman. In this study, 1185 victims of road accidents have been under supervision. Furthermore, statistical information such as age, sex, education, career, position of the occupant (Car drivers, motorcycle drivers and pedestrians), injuries related to the accident, type of vehicle, City-location of the accident and Place of death are observed. The main causes of death victims of road accidents were categorized into six groups. Occupational groups according EE0-1Job category were classified into 9 groups. Results are reported as descriptive as a frequency index (%), mean ± standard deviation, in addition, chi squared test was used to compare the clinical findings and autopsy And p Result In total 1185 people, there are 939 men (79.2%) and 246 women (20.8%). Most deaths occurred in young adult, 26.7% (19–24 years, n = 316). Injuries recorded during the autopsy examination include abrasion (n = 267, 22.5%) and laceration (n = 201, 17%) That was different significantly (p = 0.0001). In comparing of the skin lesions and Fractures between the hospital clinical records and autopsy finding, the difference was significant (p = 0.0001). The most common brain injury in hospital was epidural hematoma (n = 152, 12.8%). There was significant difference when compared with autopsy (n = 165, 13.9%) then brain contusion was most autopsy findings (n = 144, 12.2%). Whereas 141 cases was diagnosed in the hospital (11.9%) (p = 0.0001), And the diagnosis of diffuse axonal injury in both groups was similar (n = 75). Discussion The morbidity and mortality caused by head injury not only caused by traumatic brain injury, but it is sometimes due to cause delay in diagnosis and surgical procedures. We recommend abrasion & laceration injuries that could be suggestive of more serious injuries to more accurately assess the patient's bedside. Conclusion In spite the high rate of deaths in road accidents in the Iranian province of Kerman, Epidemiological data on road accidents in this area is still low. Although all improvement in clinical approach and medical facilities in Iran, a clinical diagnosis cannot be replaced autopsy in the diagnosis of death's causes. All in all, data registration and strong attention to findings of clinical tests such as laceration & abrasion is firmly encouraged to estimate of financial loss in the case of patients' survival.

Axonal microtubule (MT) bundles crosslinked by microtubule-associated protein (MAP) tau are responsible for vital biological functions such as maintaining mechanical integrity and shape of the axon as well as facilitating axonal transport. Breaking and twisting of MTs have been previously observed in damaged undulated axons. Such breaking and twisting of MTs is suggested to cause axonal swellings that lead to axonal degeneration, which is known as ''diffuse axonal injury''. In particular, overstretching and torsion of axons can potentially damage the axonal cytoskeleton. Following our previous studies on mechan- ical response of axonal MT bundles under uniaxial tension and compression, this work seeks to characterize the mechanical behavior of MT bundles under pure torsion as well as a combination of torsional and tensile loads using a coarse-grained compu- tational model. In the case of pure torsion, a competition between MAP tau tensile and MT bending energies is observed. After three turns, a transition occurs in the mechanical behavior of the bundle that is characterized by its diameter shrinkage. Further- more, crosslink spacing is shown to considerably influence the mechanical response, with larger MAP tau spacing resulting in a higher rate of turns. Therefore, MAP tau crosslinking of MT filaments protects the bundle from excessive deformation. Simulta- neous application of torsion and tension on MT bundles is shown to accelerate bundle failure, compared to pure tension experiments. MAP tau proteins fail in clusters of 10-100 elements located at the discontinuities or the ends of MT filaments. This failure occurs in a stepwise fashion, implying gradual accumulation of elastic tensile energy in crosslinks followed by rupture. Failure of large groups of interconnecting MAP tau proteins leads to detachment of MT filaments from the bundle near discontinuities. This study highlights the importance of torsional loading in axonal damage after traumatic brain injury.

Advancements in diffusion-weighted imaging during the past decade have led to the use of diffusion tensor imaging to further characterize the structural integrity of neural tissue and to noninvasively trace neuronal tracts in the brain and spine. This has led to many clinical applications that have aided in surgical planning for brain and spinal cord tumors and has increased the diagnostic potential of magnetic resonance imaging in disorders such as multiple sclerosis, Alzheimer disease, and traumatic brain injury.

Repeated blast exposures commonly induce traumatic brain injury (TBI) characterized by diffuse axonal injury (DAI). We hypothesized that degradation of cytoskeletal proteins in the brain can lead to DAI, and evaluated α-II spectrin degradation in the pathophysiology of blast-induced TBI using the tightly-coupled three repetitive blast exposure mice model with a 1-30 min window in between exposures. Degradation of α-II spectrin and the expression profiles of caspase-3 and calpain-2, the major enzymes involved in the degradation were analyzed in the frontal cortex and cerebellum using Western blotting with specific antibodies. DAI at different brain regions was evaluated by neuropathology with silver staining. Repeated blast exposures resulted in significant increases in the α-II spectrin degradation products in the frontal cortex and cerebellum compared to sham controls. Expression of active caspase-3, which degrades α-II spectrin, showed significant increase in the frontal cortex after blast exposure at all the time points studied, while cerebellum showed an acute increase which was normalized over time. The expression of another α-II spectrin degrading enzyme, calpain-2, showed a rapid increase in the frontal cortex after blast exposure and it was significantly higher in the cerebellum at later time points. Neuropathological analysis showed significant levels of DAI at the frontal cortex and cerebellum at multiple time points after repeated blast injury. In summary, repeated blast exposure results in specific degradation of α-II spectrin in the brain along with differential expression of caspase-3/calpain-2 suggesting cytoskeletal breakdown as a possible contributor of DAI after repeated blast exposure.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function.

Few long-term studies report late outcomes after severe traumatic brain injury. New rehabilitation techniques are needed for this heterogenous patient group. We present a dance intervention six and half years after an extreme severe TBI including excessive diffuse axonal injury, which disconnects the brain networks. Given the fact, that efficient brain function depends on the integrated operation of large-scale brain networks like default mode network (DMN), we created an intervention with multisensory and multimodal approach and goal-directed behavior. The intervention lasted four months including weekly one-hour dance lessons with the help of a physiotherapist and dance teacher. The measures included functional independence measure (FIM), repeated electroencephalogram (EEG) analysis of three subnets of DMN and clinical evaluations and observations. The results showed clear improvement after the intervention, and FIM stayed in elevated level during several years after the intervention. We present suggestion for further studies using larger patient groups.

OBJECTIVE: Traumatic brain injury in contact sports has significant impact on short-term neurologic and neurosurgical function as well as longer-term cognitive disability. In this study, we aim to demonstrate that contact sport participants exhibit differences in diffusion tensor imaging (DTI) caused by repeated physical impacts on the brain. We also aim to determine that impact incurred by the contact sports athletes during the season may result in the differences between the pre- and postseason DTI scans. -METHODS: DTI data were collected from 10 contact-sport (mean age 20.4 ! 1.36 years) and 13 age-matched noncontact-sport (mean age 19.5 ! 1.03 years) male athletes on a 3-Tesla magnetic resonance imaging scanner. A single-shot, echo-planar imaging sequence with b-value of 1000 s/mm 2 and 25 gradient directions was used. Eight of the athletes were again scanned after the end of the season. The b0 nondiffusion-weighted image was averaged five times. Voxelwise, two-sample t tests were run for all group comparisons, and in each case, the positive false-discovery rate was computed to assess the whole-map, multiple-comparison corrected significance. -RESULTS: There were significant differences in the fractional anisotropy valuesintheinferiorfronto-occipitalfasciculus,partsofthesuperiorandposterior coronal radiate, and the splenium of the corpus callosum (CC) as well as smaller clustersinthegenuandpartsofthebodyoftheCC.Inaddition,theexternalcapsule alsoshowssomedifferencebetweenthecontactandnoncontactathletebrains.In addition, the preseason and postseason showed differences in these regions, however, the postseason P-values show significance in more areas of the CC. -CONCLUSIONS: There are significant DTI changes in the CC, the external capsule, the inferior fronto-occipital fasciculus, as well as regions such as the superior/posterior corona radiata the preseason contact versus the noncontact control athletes were compared and also when the postseason contact athletes with the control athletes were compared. There are also differences in the DTI parameters in the post and preseason scans. Key words - Diffusion tensor imaging - Magnetic resonance imaging - Traumatic brain injury Abbreviations and Acronyms CC: Corpus callosum DTI: Diffusion tensor imaging FA: Fractional anisotropy MD: Mean diffusivity TBI: Traumatic brain injury From the 1

The principal aim in the management of patients with cerebral contusion (CC) following severe traumatic brain injury (TBI) is the prevention, amelioration, and treatment of secondary neuronal dysfunction and pathology. Distinguishing between irreversibly damaged and surviving tissue could have considerable therapeutic and prognostic implications for patients. To characterize structurally the neuronal compartment of the contused region in samples derived from patients who suffered severe TBI and were subjected to decompressive craniectomy, we used NeuN, a neuronal marker. We determined that NeuN "patches", sectors with loss of NeuN immunoreactivity (NeuN-IR), represented 25% of the area among the analyzed cases. We also found a 67% decrease in NeuN levels via Western blot. Tissue adjoining patches of NeuN-IR were considered "preserved" due to the apparent normal density of neurons and conservation of the six cortical layers. Nevertheless, these sectors retained only 39% of their neurons with the classical pattern described for normal NeuN-IR. Using Fluorojade we identified a 16-fold increase in density of moribund neurons in "preserved" sectors when compared to controls. Additionally these abnormalities were enhanced 5-fold in "patches" of NeuN-IR when compared to preserved regions. Therefore, NeuN/Fluorojade abnormalities are indicative of different cell fates characteristic of CC tissue. This analysis addressed exclusively the neuronal compartment and provides new insights into the degenerative state of neurons in the contused region that is likely to contribute to clinical outcome and differentiate TBI from ischemia.

Over the past 70 years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). Pathologically, DAI encompasses a spectrum of abnormalities from primary mechanical breaking of the axonal cytoskeleton, to transport interruption, swelling and proteolysis, through secondary physiological changes. Depending on the severity and extent of injury, these changes can manifest acutely as immediate loss of consciousness or confusion and persist as coma and/or cognitive dysfunction. In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer's disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.

Introduction Traumatic brain injury (TBI) sustained during childhood can cause difficulties in a wide range of physical, neurological, cognitive, social and functional domains. However, the ability of health professionals and researchers to accurately predict the outcome of pediatric TBI remains limited. The advent of advanced neuroimaging techniques shows some promise in improving outcome prediction, as they contribute to greater sensitivity in characterizing intracranial lesions underlying many cognitive and functional deficits. In this study, the relationship between lesions identified on susceptibility weighted imaging (SWI) and cognitive and functional outcomes was investigated following childhood TBI. Method Participants between 5 and 14 years of age with varying levels of TBI severity (mild, mild complicated, moderate, severe, n = 106) underwent susceptibility weighted scanning on average 1-month post-injury and completed an assessment of intellectual functioning, processing speed, and behavioral and adaptive skills 6-month post-injury. Results More severe TBI was generally associated with poorer intellectual functioning, greater behavioral problems and lower adaptive functioning. Number and volume of SWI lesions were significantly correlated with clinical outcome variables including Glasgow Coma Score (GCS), surgical intervention, length of hospital stay and length of intubation, as well as with intellectual functioning. Together, SWI and GCS accounted for a significant, though small, proportion of the variance in intellectual quotient (IQ). Conclusions SWI is a sensitive technique for detecting brain lesions at all TBI severity levels and shows promise in contributing to prediction of cognitive outcomes in the initial stages post-injury.

Traumatic axonal injury (TAI) is an important pathoanatomical subgroup of traumatic brain injury (TBI) and a major driver of mortality and functional impairment. Experimental models have provided insights into the effects of mechanical deformation on the neuronal cytoskeleton and the subsequent processes that drive axonal injury. There is also increasing recognition that axonal or white matter loss may progress for years post-injury and represent one mechanistic framework for progressive neurodegeneration after TBI. Previous trials of novel therapies have failed to make an impact on clinical outcome, in both TBI in general and TAI in particular. Recent advances in understanding the cellular and molecular mechanisms of injury have the potential to translate into novel therapeutic targets.

Blast traumatic brain injury (bTBI) is a leading cause of injury in the armed forces. Diffuse axonal injury, the hallmark feature of blunt TBI, has been investigated in direct mechanical loading conditions. However, recent evidence suggests inertial cavitation as a possible bTBI mechanism, particularly in the case of exposure to blast loading. Cavitation damage to free surfaces has been well-studied in the field of fluid dynamics, but bubble interactions within confined 3D environments have not been largely investigated. Cavitation occurs via a low-pressure region caused by pressure waves, and is strongly dependent on local geometric and mechanical properties. The structural damage features as the result of cavitation - particularly at the cellular level - are incompletely understood, in part due to the rapid bubble formation and strain rates of up to ∼10ˆ5-10ˆ6 s-1. This project aims to characterize material damage in 2D and 3D environments and cell cultures by utilizing a novel high-speed red-blue diffraction assisted image correlation method at speeds of up to 106 frames per second.