Diffuse Axonal Damage Research Articles

Protection against Blast-Induced Traumatic Brain Injury by Increase in Brain Volume.

Blast-induced traumatic brain injury (bTBI) is a leading cause of injuries in recent military conflicts and it is responsible for an increased number of civilian casualties by terrorist attacks. bTBI includes a variety of neuropathological changes depending on the intensity of blast overpressure (BOP) such as brain edema, neuronal degeneration, diffuse axonal damage, and vascular dysfunction with neurological manifestations of psychological and cognitive abnormalities. Internal jugular vein (IJV) compression is known to reduce intracranial compliance by causing an increase in brain volume and was shown to reduce brain damage during closed impact-induced TBI. We investigated whether IJV compression can attenuate signs of TBI in rats after exposure to BOP. Animals were exposed to three 110 ± 5 kPa BOPs separated by 30 min intervals. Exposure to BOP resulted in a significant decrease of neuronal nuclei (NeuN) together with upregulation of aquaporin-4 (AQP-4), 3-nitrotyrosine (3-NT), and endothelin 1 receptor A (ETRA) expression in frontal cortex and hippocampus one day following exposures. IJV compression attenuated this BOP-induced increase in 3-NT in cortex and ameliorated the upregulation of AQP-4 in hippocampus. These results suggest that elevated intracranial pressure and intracerebral volume have neuroprotective potential in blast-induced TBI.

Sleep Modulation Alleviates Axonal Damage and Cognitive Decline after Rodent Traumatic Brain Injury.

Traumatic brain injury (TBI) is a clinically important entity. Cognitive deficits belong to the most prevalent chronic posttraumatic symptoms, most likely due to diffuse axonal injury (DAI). A growing body of evidence suggests a role of sleep in the clearance of waste products in the brain, possibly including amyloid precursor protein (APP), a marker of DAI. In this study, we provide evidence that enhancement of slow-wave oscillatory activity in the delta-frequency range decreases the APP-immunoreactivity and preserves cognitive abilities after trauma, potentially offering novel, noninvasive treatment options for traumatic injury.

Diffuse Axonal Injury: Pathological and Clinical Aspects

Diffuse axonal and vascular injuries are the initial pathological findings in victims of diffuse brain trauma Macroscopic findings include deep contusions and multiple petechial hemorrhages primarily involving cerebral white matter basal ganglia and upper brainstem Histologically amyloid precursor protein staining still remains the gold standard for microscopic detection of diffuse axonal damage A number of other histological and immunohistochemical techniques have emerged over time aiding the diagnosis of diffuse axonal injury There has been little success however in the microscopic differentiation of traumatic from non traumatic causes of diffuse axonal injury This review explains various pathological and clinical aspects of traumatic axonal and vascular injuries including current scenarios in microscopic detection of diffuse axonal injury as well as their limitations

Novel Rat Model of Weight Drop-Induced Closed Diffuse Traumatic Brain Injury Compatible with Electrophysiological Recordings of Vigilance States.

Traumatic brain injury (TBI) is a major cause of persistent disabilities such as sleep-wake disorders (SWD). Rodent studies of SWD after TBI are scarce, however, because of lack of appropriate TBI models reproducing acceleration-deceleration forces and compatible with electroencephalography/myography (EEG/EMG)-based recordings of vigilance states. We therefore adapted the Marmarou impact acceleration model to allow for compatibility with EEG-headset implantation. After implantation of EEG/EMG electrodes, we induced closed TBI by a frontal, angular hit with a weight-drop device (56 rats, weight 2500 g, fall height 25 cm). Subsequently, we tested our model's usefulness for long-term studies on a behavioral, electrophysiological, and histological level. Neurological, motor, and memory deficits were assessed with the neurological severity score, open field, and novel object recognition tests, respectively. EEG/EMG recordings were performed in both Sham (n = 7) and TBI (n = 7) rats before and 1, 7, and 28 days after trauma to evaluate sleep-wake proportions and post-traumatic implant stability. Histological assessments included hematoxylin and eosin staining for parenchymal damage and hemorrhage and amyloid precursor protein staining for diffuse axonal damage. All rats survived TBI without major neurological or motor deficits. Memory function was impaired after TBI at weeks 1, 2, and 3 and recovered at week 4. EEG implants were stable for at least 1 month and enabled qualitative and quantitative sleep analyses. Histological assessments revealed no major bleedings or necrosis but intense diffuse axonal damage after TBI. This approach fulfills major pre-conditions for experimental TBI models and offers a possibility to electrophysiologically study behavioral states before and after trauma.

Changes in music listening in post-concussion syndrome after mild traumatic brain injury.

Mild traumatic brain injury (MTBI) constitutes a public health problem with major socioeconomic consequences (Maas, Stocchetti, & Bullock, 2008). The notion of post-concussion syndrome (PCS) following MTBI is now a well-described (Borg et al., 2004) and extensively discussed concept (Rees, 2003; Wood, 2007). However, current standard imaging (mainly MRI) techniques rarely reveal abnormalities, and the consequences of diffuse axonal damage are difficult to document. For these reasons, PCS is often considered to be either psychogenic in origin (Whittaker, Kemp, & House, 2007)ora fallacious pretext for financial compensation. However, it is clear that new MR imaging methods such as MRI diffusion anisotropy (Belanger, Vanderploeg, Curtiss, & Warden, 2007; Maller et al., 2010) and magnetic resonance spectroscopy (MRS; Garnett et al., 2000; Govindaraju et al., 2004) can reveal structural and metabolic white matter abnormalities in connection with post-concussion symptoms, including depression (Maller et al., 2010). A significant proportion (5-7%) of patients with MTBI present a later cognitive decline (Hammond et al., 2004). Recent studies conducted on 2525 U.S. soldiers exposed to blasts and who suffered MTBI clearly reveal the neurological correlates of PCS and indicate that PCS is closely associated with loss of consciousness during the trauma (Hoge et al., 2008). The link between cognitive deficits related to PCS and impairment of brain connectivity, particularly in frontal regions, has been recently demonstrated (Sponheim et al., 2011).Apart from a few music-related pathologies (congenital amusia, musicogenic epileptic seizures), few studies have reported abnorCeline malities of listening to or producing music in neurological and psychiatric pathologies (Vion-Dury & Besson, 2010). However, throughout human history, billions of human beings have created and listened to sound patterns and sequences that do not carry any denotative meaning (Sacks, 2008). In this respect, Andrade and Bhattacharya (2003) proposed that the brain is tuned to music. Although many studies emphasize the value of music therapy in patients with various neurological and psychiatric diseases, the scientific literature exploring changes in the quality of music listening is sparse. Sacks presented many clinical examples related to this issue (Sacks, 2008), but only a few examples of any given pathology are available to the best of our knowledge.The current study stems from a clinical observation: during individual interviews prior to neurophysiological assessment of PCS following an MTBI, several patients reported an experience of disruption, with alterations of their capacity to evaluate durations and the feeling of being disoriented in time. This led us to question them about changes in their music listening habits because music can be regarded as an art of time (Emery, 2000); thus, its appreciation requires precise processing of temporal structures at different scales (Accaoui, 2001). Following the question Has your way of listening to music changed since your brain trauma?, patients remained silent for several seconds. Then, they reported being aware that their music listening habits had changed. However, they were unable to accurately describe this modification. This recurrent clinical observation gave rise to this study, the aim of which was to assess musicrelated changes in patients suffering from MTBI, by combining both objective and subjective data experienced in the firstperson, according to the neurophenomenological approach (Vion-Dury, 2007; Vion-Dury et al., 2011) and by analyzing if these music-related changes are correlated to any abnormality in imaging, neuropsychological, or neurophysiologic evaluation.MethodSubjectsThis study took place during a global assessment of the PCS diagnosis in MTBI patients, as organized by the Groupe d'Etudes des Professionnels Alpes-Mediterranee sur les Traumatismes Crâniens (GREPAM-TC), from October 2008 to June 2009 (Soriat-Barriere, Tcherniack, & Vion-Dury, 2011). …

Decreasing incidence of paroxysmal sympathetic hyperactivity syndrome in the vegetative state

To update knowledge of the incidence of paroxysmal sympathetic hyperactivity (PSH, also referred to as dysautonomia), an emergency condition tentatively attributed to sympathetic paroxysms or diencephalic-hypothalamic disarrangement associated with severe diffuse brain axonal damage or hypoxia. This condition is reportedly common in the vegetative state, threatens survival and affects outcome. The results of a retrospective study on 333 subjects in a vegetative state admitted to a dedicated unit in 1998-2005 are compared with a survey on patients admitted to the same unit in 2006-2010. In the 1998-2005 period, the incidence of PSH was 32% and 16% in post-traumatic and non-traumatic patients, respectively. It decreased to 18% and 7% in the 2006-2010 period. The PSH duration and the time spent in emergency units before admission and in the dedicated unit for the vegetative state after admission also decreased significantly. Incidence was greater among post-traumatic- patients; its effect on outcome does not appear to have changed.

The Neuropathology of Fatal Cerebral Malaria in Malawian Children

We examined the brains of 50 Malawian children who satisfied the clinical definition of cerebral malaria (CM) during life; 37 children had sequestration of infected red blood cells (iRBCs) and no other cause of death, and 13 had a nonmalarial cause of death with no cerebral sequestration. For comparison, 18 patients with coma and no parasitemia were included. We subdivided the 37 CM cases into two groups based on the cerebral microvasculature pathology: iRBC sequestration only (CM1) or sequestration with intravascular and perivascular pathology (CM2). We characterized and quantified the axonal and myelin damage, blood-brain barrier (BBB) disruption, and cellular immune responses and correlated these changes with iRBC sequestration and microvascular pathology. Axonal and myelin damage was associated with ring hemorrhages and vascular thrombosis in the cerebral and cerebellar white matter and brainstem of the CM2 cases. Diffuse axonal and myelin damage were present in CM1 and CM2 cases in areas of prominent iRBC sequestration. Disruption of the BBB was associated with ring hemorrhages and vascular thrombosis in CM2 cases and with sequestration in both CM1 and CM2 groups. Monocytes with phagocytosed hemozoin accumulated within microvessels containing iRBCs in CM2 cases but were not present in the adjacent neuropil. These findings are consistent with a link between iRBC sequestration and intravascular and perivascular pathology in fatal pediatric CM, resulting in myelin damage, axonal injury, and breakdown of the BBB.

Heterogeneous Pattern of Retinal Nerve Fiber Layer in Multiple Sclerosis. High Resolution Optical Coherence Tomography: Potential and Limitations

BackgroundRecently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique.MethodologyForty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP).Principal FindingsAll 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9–540 months).ConclusionsRNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).

A polytrauma patient with an unusual posterior fracture-dislocation of the femoral head: a case report

We report a case of a 27-year-old man who was involved in a high-speed car accident. He sustained multiple organ damage including multiple brain petechiae suggesting diffuse axonal damage, aortic dissection, retroperitoneal haematoma and a fracture-dislocation of the right hip with a femoral head fracture and an ipsilateral intertrochanteric fracture. Due to the general condition of the patient, physiological stabilisation was prioritized, and at 2 weeks the fracture-dislocation of the hip was treated with a proximal femoral nail for the intertrochanteric fracture and Herbert screws for the femoral head fracture. Postoperatively, two episodes of recurrent hip dislocation occurred, and this was stabilized eventually with a Steinman pin inserted across the hip joint and taken out 1 month later. Weight-bearing was allowed according to clinical and radiographical assessments. Heterotopic ossification developed around the hip joint, but without evidence of AVN or osteoarthritis. At 18-months follow-up, the fractures had healed and the patient had a Harris Hip score of 79.1. Anatomical reduction and stable fixation of fracture-dislocations of the hip are important for achieving an acceptable result.

Graded model of diffuse axonal injury for studying head injury‐induced cognitive dysfunction in rats

Diffuse axonal injury (DAI) plays a major role in the development of cognitive dysfunction, emotional difficulties and behavioral disturbances in patients following closed head injury, even when they have no definite abnormalities on conventional MRI. This study aimed to develop a highly controlled and reproducible model for DAI that simulates post-traumatic cognitive dysfunction in humans. Sprague-Dawley (SD) rats were subjected to impact acceleration head injury, using a pneumatic impact targeted to a steel disc centered onto their skull. The severity of injury was graded as three levels by adjusting the driving pressure at 60, 70 or 80 pounds per square inch. In vivo MRI was obtained 2 days post-injury. Cognitive function was evaluated using the Morris water maze at 1 and 2 weeks post-injury. HE staining and immunohistochemistry were performed to assess neuronal and axonal damages after 2 weeks. MRI demonstrated that this model induced no gross structural modification in the brain. The degree and duration of cognitive dysfunction were dependent on the force of impact. Histological analysis revealed the force-dependent damage of the neurons and microtubule-associated protein 2-positive axons in the neocortex. Hippocampal damage was much less pronounced and was not linked to cognitive dysfunction. This is the first report that precisely evaluates the threshold of impact energy to lead to neocortical damage and cognitive dysfunction in rodents. This model would be suitable for clarifying the complex mechanisms of post-traumatic brain damage and testing novel therapeutic approaches against post-traumatic cognitive dysfunction due to diffuse axonal damage.

Crossbow injuries: A case report

Despite the increasing popularity of crossbows in recreational hunting, injuries and deaths from crossbows are still relatively rare. In suicides, the body areas favoured are similar to those of gun users, namely the thorax and head. These deaths almost always occur in males. The case presented is that of a 49 year old male with a history of mental illness and suicidal attempts, who committed suicide with a crossbow. The weapon was discharged into the left thorax. Examination of crossbow injuries can be difficult due to their similarities with other incised wound patterns. As many victims may survive for some time after injury, removal of the bolt is possible. As well, removal of the bolt followed by advanced decomposition may alter the wound patterns. Careful examination of clothing, as well as entry wound reconstruction may give an indication to the weaponry used. Radiology is useful for detecting debris along the wound path, as well as position of the bolt when it is in situ. Finally, when dealing with cases of crossbow head injuries, consideration of both blood loss as well as diffuse axonal damage is important, both in non-fatal and fatal cases.

Diffuse Axonal Injury in Periventricular Leukomalacia as Determined by Apoptotic Marker Fractin

Periventricular leukomalacia (PVL), the major substrate of neurologic deficits in premature infants, is associated with reduced white matter volume. Using immunomarkers of axonal pathology [beta-amyloid precursor protein (beta-APP) and apoptotic marker fractin], we tested the hypothesis that widespread (diffuse) axonal injury occurs in the gliotic white matter beyond the foci of necrosis in PVL, thus contributing to the white matter volume reduction. In a cohort of 17 control cases and 13 PVL cases with lesions of different chronological ages, diffuse axonal damage in PVL was detected by fractin in white matter sites surrounding and distant from acute and organizing foci of necrosis. Using beta-APP, axonal spheroids were detected within necrotic foci in the acute and organizing (subacute) stages, a finding consistent with others. Interestingly, GAP-43 expression was also detected in spheroids in the necrotic foci, suggesting attempts at axonal regeneration. Thirty-one percent of the PVL cases had thalamic damage and 15% neuronal injury in the cerebral cortex overlying PVL. We conclude that diffuse axonal injury, as determined by apoptotic marker fractin, occurs in PVL and that its cause likely includes primary ischemia and trophic degeneration secondary to corticothalamic neuronal damage.

Kafa Travmalarında Diffüz Akson Zararı Tanıda B-App’nin Yeri

Farklı derecelerde kafa travması geçirmiş olan kişilerde ölümün ya da uzamış nörolojik defisitlerin en önemli nedenlerinden biri diffüz akson zararıdır (DAZ). Otopsi olgularında DAZ’ın tanısı beynin uygun bölgelerinden alınacak örneklerde Hematoksilen Eozin ile boyanmış kesitlerin mikroskopik incelenmesi ile mümkündür. Ancak, posttravmatik dönemde çok kısa süre yaşamış olan olgularda zararın morfolojik bulguları tam oluşmadığından bu olgularda DAZ’ın tanınması zordur. ß-APP bu tür olgularda DAZ’in tanınabilmesinde önemli rol oynamaktadır. Canlı iken gerçekleşmiş olan zararı yansıtması, sadece zarar görmüş aksonları işaretlemesi ve postmortem in-tervalden etkilenmemesi en önemli üstünlükleridir. Çalışmanın amacı, DAZ’ın oluş mekanizması ile morfolojik bulgularını gözden geçirmek, kafa travması geçirmiş olguların değerlendirilmesinde ß-APP’nin rolü ve önemini vurgulamaktır.Anahtar kelimeler: Travma, beyin, diffüz akson zararı, ß-APP

Diffuse Axonal Damage, Myelin Impairment, Astrocytosis and Inflammatory Response Following Microinjections of NMDA into The Rat Striatum

White matter damage and inflammatory response are important secondary outcomes after acute neural disorders. Nevertheless, a few studies addressed the temporal outcomes of these pathological events using non-traumatic models of acute brain injury. In the present study, we describe acute inflammatory response and white matter neuropathology between 1 and 7 days after acute excitotoxic striatal damage. Twenty micrometer sections were stained by hematoxylin and eosin technique for gross histopathological analysis and immunolabed for neutrophils (anti-mbs-1), activated macrophages/microglia (anti-ed1), astrocytes (anti-gfap), damaged axons (anti-betaapp) and myelin basic protein (MBP). Recruitment peak of neutrophils and macrophages occurred at 1 and 7 days post-nmda injection, respectively. Diffuse damaged axons (beta-app + end-bulbs) were apparent at 7 days, concomitant with progressive myelin impairment and astrocytosis. Further studies using electron microscopy and blockers of inflammatory response and glutamatergic receptors should be performed to confirm and address the mechanisms of white matter damage following an excitotoxic lesion.

Farmacoterapia de las secuelas cognitivas secundarias a traumatismo craneoencefálico

To review and correlate the most common cognitive disorders secondary to traumatic brain injuries (TBI), the neurobiology of these deficits and their possible modulation by neuropharmacological means.As of a complex cascade of injuries to the brain, patients with TBI may experience alterations that affect the cognitive domain on different levels and to varying degrees, the most common being alteration of the level of alertness; slowing of the speed at which information is processed; attention, memory and learning deficits; language and communication disorders; and impaired executive functions. Brain damage may be caused by a range of pathological mechanisms, such as focal bruising, diffuse axonal damage, cytotoxic damage and neurotransmitter excitotoxicity. Certain pharmacological agents have an effect on the cognitive functions. Pharmacological agents that improve cognitive performance include dopaminergic agents, psychostimulants, some antidepressants and cholinesterase inhibitors.Studies into the pharmacological neuromodulation of the cognitive disorders secondary to TBI are currently in the early stages. The information we have available on the neurochemical bases of cognition and cognitive disorders due to TBI suggest that the most important goals of pharmacological intervention in this group of patients are the stimulation of the catecholaminic and cholinergic functions.

Understanding fatigue in multiple sclerosis: new insights in causes and assessment

Fatigue is one of the most common symptoms encountered in multiple sclerosis (MS), and research is continuously improving the knowledge and assessment of this specific field. There are growing and clear indications that an important role in determining fatigue is played by ‘central’ abnormalities and dysfunctions. Recent studies have focused on the correlations between diffuse axonal damage, brain atrophy and fatigue. New innovative scales are available to measure fatigue, and the nature of the relationship between depression and fatigue in MS is still under debate.

Lesión traumática del tronco cerebral diagnosticada por resonancia magnética: Reconsideración epidemiológica y pronóstica

CT-scan allows emergency surgical evaluation of head injury lesions, but does not offer a comprehensive diagnosis of the resulting brain injuries. Magnetic Resonance Imaging (MRI) can complete the evaluation of head injury, particularly in the brain stem. We attempted to estimate the frequency of traumatic primary brain stem injuries Thirty patients with moderate or severe head injury (GCS < or = 13) underwent a MRI study during the first two weeks after trauma. In order to exclude old patients with previous ischemic lesions unrelated to the head trauma, only young patients (16-40 years-old) were included. Patients with cranial surgery were also eliminated from the study. Based on previous studies, the FLAIR (8000/120/T. Inversion 2200mseg) sequence was selected. Brain stem injuries were detected in 26.6% of the patients; this was confirmed by two independent radiologists. Six patients had hyperintense lesions compatible with diffuse axonal damage, and two others showed hemorrhagic lesions. These findings were directly related to a specific neurological deficit in four patients; while in the remaining, unspecific consciousness disturbances were noted. We believe that the FLAIR sequence demonstrate a type of traumatic brain stem injury (probably corresponding to diffuse axonal injury) that is more frequent and less severe in terms of prognosis than those classically described in previous CT scan studies.

Update of Neuropathology and Neurological Recovery After Traumatic Brain Injury

This review focuses on the potential for traumatic brain injury to evoke both focal and diffuse changes within the brain parenchyma, while considering the cellular constituents involved and the subcellular perturbations that contribute to their dysfunction. New insight is provided on the pathobiology of traumatically induced cell body injury and diffuse axonal damage. The consequences of axonal damage in terms of subsequent deafferentation and any potential retrograde cell death and atrophy are addressed. The regional and global metabolic sequelae are also considered. This detailed presentation of the neuropathological consequences of traumatic brain injury is used to set the stage for better appreciating the neurological recovery occurring after traumatic injury. Although the pathological and clinical effects of focal and diffuse damage are usually intermingled, the different clinical manifestations of recovery patterns associated with focal versus diffuse injuries are presented. The recognizable patterns of recovery, involving unconsciousness, posttraumatic confusion/amnesia, and postconfusional restoration, that typically occur across the full spectrum of diffuse injury are described, recognizing that the patient's long-term recovery may involve more idiosyncratic combinations of dysfunction. The review highlights the relationship of focal lesions to localizing syndromes that may be embedded in the evolving natural history of diffuse pathology. It is noted that injuries with primarily focal pathology do not necessarily follow a comparable pattern of recovery with distinct phases. Potential linkages of these recovery patterns to the known neuropathological sequelae of injury and various reparative mechanisms are considered and it is proposed that potential biological markers and newer imaging technologies will better define these linkages.

The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats

Experimental models of traumatic brain injury have been developed to replicate selected aspects of human head injury, such as contusion, concussion, and/or diffuse axonal injury. Although diffuse axonal injury is a major feature of clinical head injury, relatively few experimental models of diffuse traumatic brain injury (TBI) have been developed, particularly in smaller animals such as rodents. Here, we describe the pathophysiological consequences of moderate diffuse TBI in rats generated by a newly developed, highly controlled, and reproducible model. This model of TBI caused brain edema beginning 20 min after injury and peaking at 24 h post-trauma, as shown by wet weight/dry weight ratios and diffusion-weighted magnetic resonance imaging. Increased permeability of the blood–brain barrier was present up to 4 h post-injury as evaluated using Evans blue dye. Phosphorus magnetic resonance spectroscopy showed significant declines in brain-free magnesium concentration and reduced cytosolic phosphorylation potential at 4 h post-injury. Diffuse axonal damage was demonstrated using manganese-enhanced magnetic resonance imaging, and intracerebral injection of a fluorescent vital dye (Fluoro-Ruby) at 24-h and 7-day post-injury. Morphological evidence of apoptosis and caspase-3 activation were also found in the cerebral hemisphere and brainstem at 24 h after trauma. These results show that this model is capable of reproducing major biochemical and neurological changes of diffuse clinical TBI.

The conformation of the brain plays an important role in the distribution of diffuse axonal injury in fatal road traffic accident.

A study was made of the brain lesions in 120 random victims of fatal road traffic accidents to determine the frequency and topographic distribution of diffuse axonal damage (DAI) in relation to the midline brain structures. The identification of axons was carried out with a mouse antibody anti-neurofilament proteins 70-, 160-, and 210-kD. DAI was identified in 96 (80%) brains and classified as Grade 1 in 21.9%, as Grade 2 in 51%, and as Grade 3 in 27.1% of the patients. In spite of the diffuse distribution that is characteristic of DAI, damage occurred preferentially in the interhemispheric formations (corpus callosum and fornix) and rostral portion of the brainstem, usually to one side of the midline. From a mechanical point of view, the interhemispheric formations and the rostral portion of the brainstem act as fixating structures for the cerebral hemispheres during rotational acceleration of the head. It is known that the motion of the cerebral hemispheres is delayed at the points of fixation, where greater stress would be produced, particularly on the side subjected to greater displacement. The frequent involvement by DAI of deep, center-medial brain structures, usually to one side of the midline, supports the mechanism proposed above.