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PubMed1992

Pathological study of diffuse axonal injury patients who died shortly after impact.

It is generally considered that axonal injury is apparent only on electron microscopy in the very early stage after a closed head injury. To clarify the pathological findings in head injury patients dying very shortly after the impact, we analyzed 8 fatal cases of diffuse axonal injury (DAI) who underwent medicolegal autopsy at the Department of Forensic Medicine of Kyoto Prefectural University of Medicine. Seven cases died within one hour after injury and another one case died 3 days after injury. We studied these cases macroscopically, microscopically, and electron microscopically. Macroscopically all cases showed the typical findings of diffuse axonal injury. Microscopical study of the cases who died within one hour revealed no characteristic findings of DAI such as appearance of retraction balls or microglia. On the other hand, in the case who died only 3 days after injury it showed the typical retraction balls. Electron microscopic study showed the remarkable destruction of cytoskeletal structure of axons in all cases. From our results, it is reasonable to speculate that DAI may be common among head injury patients who die very soon after the impact.

Adolescent↗
PubMed2004

[Neurobehavior changes of rats after diffuse axonal injury and the treatment effect with cyclosporin A].

OBJECTIVE: To observe rat's memory and learning behavior after diffuse axonal injury (DAI) and evaluate the treatment efficacy of cyclosporin A (CsA). METHODS: Twenty-four SD rats were divided into three groups: non-injured group (n=8), vehicle-treated group (n=8) to whom saline was applied and CsA-treated group (n=8). By analyzing behavior changes of rats in Morris water maze and dark-avoidance test, the CsA treatment efficacy was evaluated. RESULTS: The Morris water maze was used to observe rats' memory and learning behavior. During a place-training experiment, the latency to find platform in each trial descended remarkably. Vehicle-treated group exhibited acquisition deficits compared with CsA-treatment group. The latency in each trial was longer in vehicle-treated group (F=60.44, P<0.01). With continued training, the rats' performance in CsA-treatment group was better than those in control brain-injured group in crossing platform test (F=-4.00, P<0.01), but no difference with the normal group. In dark-avoidance test, the rats in normal control group had remembered the electricity shock very fast, and seldom entered into dark chamber. The mean latency time was (292.88+/-12.61) seconds. The latency time of rats in CsA-treated group was (224.75+/-55.95) seconds. The latency time of rats in vehicle-treated group was (153.25+/-69.36) seconds. The time of rats in CsA-treated group was shorter than the time of vehicle-treated group animal(F=-71.50, P<0.05). CONCLUSION: The rats' memory function is impaired after DAI. The learning acquisition and memory retention impairments are ameliorated after administration of CsA.

Animals↗
PubMed1982

Diffuse axonal injury due to nonmissile head injury in humans: an analysis of 45 cases.

Forty-five cases of diffuse axonal injury (DAI) brought about by nonmissile head injury in humans are analyzed and compared with 132 cases of fatal head injury without DAI. All cases were subjected to a comprehensive neuropathological study. In the patients with DAI a statistically significant lower incidence of lucid interval, fracture of the skull, cerebral contusions, intracranial hematoma, and evidence of high intracranial pressure were found, with a higher incidence of head injury due to road traffic accident. Brain swelling and hypoxic brain damage were not statistically different in the two groups. The features of DAI in humans are compared with the DAI that has been produced in subhuman primates by pure inertial loading brought about by angular acceleration of the head. The available evidence indicates that DAI in human beings occurs at the time of head injury and is not due to complicating factors such as hypoxia, brain swelling, or raised intracranial pressure.

Adolescent↗
PubMed1998

Extradural haematoma and diffuse axonal injury in victims of fatal road traffic accidents.

Seven cases of victims of road traffic accidents with extradural haematoma (EH) and diffuse axonal injury (DAI) are reported. Such cases are part of a total of 120 victims of fatal road traffic accidents that were subjected to pathological study. The association of the two lesions occurred in 5.8% of the patients and all cases of EH were associated with DAI. The latter explains the immediate coma (absence of lucid interval) and the grave prognosis for all seven patients. It was noted that EH is relatively infrequent in road traffic accidents, but in such cases it is more severe since it is frequently associated with DAI and immediate coma.

Accidents, Traffic↗
PubMed2005

Diagnosis and treatment of diffuse axonal injury in 169 patients.

OBJECTIVE: To evaluate current diagnosis and therapeutic effect and outcome of diffuse axonal injury (DAI) in 169 patients. METHODS: The data of 169 DAI patients treated in the Second, Sixth, Eighth and Ninth Hospitals of Shenzhen and Shekou Hospital from January 2001 to January 2005 were collected. The imaging features, classification, GCS (Glasgow coma scale), treatment and outcome of the 169 patients were retrospectively analyzed. RESULTS: The simpler the imaging features, the closer the focus of DAI to the periphery of hemisphere and the higher the GCS score, the better the prognoses of DAI patients will be. CONCLUSIONS: The prognoses of DAI patients are closely related to the imaging features and classification, GCS and clinical treatment.

Journal Article↗
PubMed1989

[Significance of magnetic resonance imaging in diffuse axonal injury].

Advantages of magnetic resonance imaging (MRI) to computed tomography (CT) on a diagnosis of diffuse axonal injury (DAI) were discussed. Sixteen patients diagnosed as DAI defined by the criteria of Gennarelli were studied with CT and MRI. Lesions were demonstrated as high intensity areas on MRI of T2 weighted imaging (SE 2000/111) in all of the patients. These lesions were located only in a cerebral white matter in the cases of mild DAI, whereas in the cases of severe DAI located in a basal ganglia, corpus callosum, dorsal part of the brain stem as well as in the cerebral white matter. As for the findings of CT, these parenchymal lesions were not visualized in nine cases including six cases without any pathological findings. Our series suggest that MRI is superior to CT on the diagnosis of DAI and provides some information to evaluate the severity of DAI.

Adolescent↗
PubMed2003

Acute subdural hematoma and diffuse axonal injury in fatal road traffic accident victims: a clinico-pathological study of 15 patients.

OBJECTIVE: Although acute subdural hematoma (ASDH) and diffuse axonal injury (DAI) are commonly associated in victims of head injury due to road traffic accidents, there are only two clinico-pathological studies of this association. We report a clinical and pathological study of 15 patients with ASDH associated with DAI. METHOD: The patients were victims of road traffic accidents and were randomly chosen. The state of consciousness on hospital admission was evaluated by the Glasgow coma scale. For the identification of axons the histological sections of the brain were stained with anti-neurofilament proteins. RESULTS: Twelve of the 15 patients were admitted to hospital in a state of coma; in three patients, the level of consciousness was not evaluated, as they died before hospital admission. CONCLUSION: The poorer prognosis in patients with ASDH who lapse into coma immediately after sustaining a head injury, as described by several authors, can be explained by the almost constant association between ASDH and DAI in victims of fatal road traffic accidents.

Accidents, Traffic↗
PubMed2000

The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid-percussive brain injury in rats.

The immunolocalization of tumor necrosis factor-alpha (TNF alpha) after diffuse axonal injury (DAI) is demonstrated using a midline fluid percussion rat model (moderate brain injury of 1000 mm Hg was generated) and the effects of TNF alpha on the axolemmal permeability using horseradish peroxidase as a tracer. In addition, the accumulation of beta-amyloid precursor protein (beta-APP) was investigated, which has recently been shown to be a reliable marker for the diagnosis of DAI in cases with fatal head injury. TNF alpha levels in brain tissues from the impact site and the cortex including the corpus callosum, gradually increased during the first 1 h, rose to a maximal elevation at 3 h, gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase (HRP) tracer experiments revealed that primary axonal damage appeared as early as 15 min after impact but rapidly recovered and that 1 h after impact, secondary axonal damage occurred in the corpus callosum and the brain stem. By immunoelectron microscopy it was seen that beta-APP accumulated in the axon from 1 h after impact demonstrating that there was functional axonal damage. TNF alpha reactions were detected in the lysosomes of microglia 30 min after impact and 1 h after impact these reactions were mainly detected in the glial cells (such as microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain stem. It is generally accepted that TNF alpha directly induces primary demyelination and oligodendrocyte apoptosis. Therefore, TNF alpha conveyed from the microglial cells is one cofactor contributing to the formation of the delayed axonal damage observed at these sites. The present study suggests that TNF alpha conveyed from the glial cells may contribute to the pathogenic mechanism of DAI formation following fluid percussive brain injury.

Amyloid beta-Protein Precursor↗
PubMed2006

Compensatory cortical activation during performance of an attention task by patients with diffuse axonal injury: a functional magnetic resonance imaging study.

OBJECTIVE: To determine how cortical compensation occurs in higher cognitive systems during the recovery phase of diffuse axonal injury (DAI). DESIGN: 12 right-handed patients with a magnetic resonance imaging (MRI) lesion pattern compatible with pure DAI were identified. Pure DAI was defined as finding of traumatic microbleeds on T2*-weighted gradient-echo images in the absence of otherwise traumatic or non-traumatic MRI abnormalities. 12 matched healthy controls were also enrolled. Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory test (Paced Visual Serial Attention Test (PVSAT)). RESULTS: No significant group differences were observed in reaction times for the PVSAT. Although patients with pure DAI committed a few errors during the PVSAT, controls respond correctly to each probe. Controls showed activations in the left frontal gyrus, left parietal gyrus and right inferior parietal gyrus. Patients with pure DAI showed activations in the left inferior frontal gyrus, right inferior frontal gyrus and right middle frontal gyrus. Between-group analysis of the PVSAT task showed significantly greater activation of the right inferior frontal gyrus (BA 45) and right middle frontal gyrus (BA 9) in patient with pure DAI versus controls. CONCLUSIONS: Patients with pure DAI require compensatory activation of the contralateral (right) prefrontal region to carry out activities similar to healthy controls. These findings provide further evidence for the adaptive capacity of neuronal systems and brain plasticity during the recovery stages of DAI.

Adolescent↗
PubMed2002

[An infant with diffuse axonal injury].

Development of MRI enabled accurate and rapid diagnosis of head traumas which had been impossible with the conventional CT. The diagnosis of posttraumatic diffuse axonal injury (DAI) is a typical example. Most of the reported cases of DAI in childhood are of relatively older age, and DAI is rare in infancy. We report here a 1-year-9-month-old infant with DAI. After falling from two meters in height, he presented consciousness disturbance and a seizure that necessitated artificial respiration for half a day. He recovered completely without sequelae. Brain CT on arrival to the ER department was unremarkable, but MRI scans shortly thereafter showed typical findings of DAI. In childhood, DAI tends to be milder than in adult-hood, which may be explained by the age-dependent frequency of traffic accidents, and by anatomical and functional factors of a infant's brain. A large number of infantile cases should be accumulated to draw a more clearcut conclusion.

Brain↗
PubMed2005

Lesions identified on T2*-weighted gradient echo images in two patients with suspected diffuse axonal injury that resolved in less than ten days.

T2*-weighted gradient echo (GE) imaging is useful for detection of intracranial hemorrhage in the patients with diffusion axonal injury (DAI). However, the temporal changes in the DAI-related lesions on T2*-weighted GE images are not clear. We report two very rare cases with DAI in which lesions identified on T2*-weighted GE images resolved in less than ten days.

Adolescent↗
PubMed2005

Motor recovery mechanism of diffuse axonal injury: a combined study of transcranial magnetic stimulation and functional MRI.

PURPOSE: The purpose of this study was to investigate the motor recovery mechanism following diffuse axonal injury (DAI) using transcranial magnetic stimulation (TMS) and functional MRI (fMRI). METHODS: Twenty-six hands of 13 control subjects and 14 affected hands of 8 patients (two hemiparetics and six quadriparetics) were evaluated. All the patients were initially diagnosed with DAI and were evaluated after they had reached their maximal motor recovery. fMRI was performed at 1.5 T using a hand grasp-release movement paradigm and TMS was applied with a round coil over the vertex. RESULTS: fMRI revealed that both normal subjects and patients with DAI showed increased contralateral primary sensori-motor cortex activation during affected hand movement. The motor evoked potentials (MEPs) of the patient group was slightly delayed in latency and significantly increased in duration and turns. The relative MEP amplitude, phase, and excitatory threshold were not significantly different between the groups. CONCLUSIONS: These findings may indicate the heterogeneity of the axons in the recovery process of the corticospinal tract. It seems that the motor recovery in patients who had suffered DAI was attributable to the recovery of the corticospinal tract.

Adult↗
PubMed1997

Evaluation of learning and memory dysfunction and histological findings in rats with chronic stage contusion and diffuse axonal injury.

We previously reported a modified fluid percussion device capable of consistently producing experimental cortical contusion (CC) and diffuse axonal injury (DAI) in separate groups of rats by lateral and midline fluid percussion, respectively. The purpose of the present study was to compare the differences in learning acquisition and memory retention impairments between these two types of injured rats in the chronic stage using the Morris water maze technique. We also compared the histological differences between these two different types of traumatic brain injury. The results showed a statistically significant difference in learning acquisition impairment between the sham and CC rats and also between the sham and DAI rats. However, a significant difference in memory retention impairment was observed only between the sham and DAI rats. Histologically, the neuronal cell loss of CA3 pyramidal cells in the hippocampus was observed on the ipsilateral side in the CC and bilaterally in DAI. The neuronal cell loss was seen in bilateral entorhinal cortex layer II in DAI, but it was not seen in CC. From these results, we speculate that the marked cell loss in the hippocampus CA3 region in both CC and DAI rats was related to the impairment of spatial learning acquisition. The marked cell loss in entorhinal cortex layer II in DAI rats may be one of the important factors in the impairment of spatial memory retention.

Animals↗
PubMed2001

Simulation of acute subdural hematoma and diffuse axonal injury in coronal head impact.

Coronal head impacts were simulated in a physical model, based on the hypothesis that acute subdural hematoma (ASDH) is related to cerebral vertex displacement and diffuse axonal injury (DAI) to local Green-Lagrange strain. The geometry of the 2D model was based on anatomical measurements taken from the MRI scans of 10 adult males. Silicone gel modelled the cerebrum, paraffin the CSF and elastic membranes the trabeculae of the sulci. Pendulum impacts gave peak angular acceleration of 7800 rad s(-2) in models with and without sulci. The motion of the gel and Green-Lagrange strain were calculated from tracked coordinates of Patrick markers. Worst-case bridging vein strains are produced on the contrecoup side and are approximately doubled by adding sulci. Given that axons in the corpus callosum are highly oriented, Green-Lagrange strain was resolved in the fibre direction. It is found to be close to the minimum principal strain, indicating a degree of natural, teleological protection for the axons. The data support the use of delta0peak as a suitable descriptor for the risk of DAI but not for ASDH.

Adult↗
PubMed2006

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment.

The present study used short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI) to evaluate motor cortex excitability in 16 diffuse axonal injury (DAI) patients with memory impairment and compared the data with those of 16 healthy controls. SAI was reduced in patients compared with controls (92+/-12 versus 39+/-11% of the test size; p<0.0001, unpaired t-test). DAI patients tended to have a high resting motor threshold (RMT) and less pronounced SICI and ICF than controls, but these differences were not significant. A single oral dose (3mg) of donepezil, an acetylcholinesterase inhibitor that is commonly used to treat Alzheimer's disease (AD), improved SAI in DAI patients with wide individual variations that ranged from an increase of 77-18% of test size. These findings suggest that measuring SAI may provide a means of probing the integrity of cholinergic networks in an injured human brain.

Adult↗
PubMed1994

The pathological spectrum of diffuse axonal injury in blunt head trauma: assessment with axon and myelin strains.

Although diffuse axonal injury (DAI) has been described as a major form of primary damage to the brain in blunt head injury, there has been no systematic study of the pathological changes in different regions of the brain. In this study, 22 cases of DAI were comprehensively examined histologically in the following areas: corpus callosum, internal capsule, superior cerebellar peduncles, cerebral white matter, fornix, rostral brain stem and globus pallidus, with a total of 17 standard blocks in each case. Sections were stained for axons with Glees and Marsland and neurofilament immunostaining and myelin with luxol fast blue and myelin basic protein immunostaining, and axonal retraction balls and myelin globoids were counted. Neurofilament immunostaining was superior to Glees and Marsland in both the positivity rates and the actual scores. Small myelin globoids were identified by the myelin stains, probably as a form of myelin damage secondary to axonal disruption. Such acute myelin damage was previously undescribed. There was no significant difference in both positivity rates and the scores obtained for luxol fast blue and myelin basic protein. Of all the regions of the brain examined, the internal capsule, corpus callosum and superior cerebellar peduncles yielded the highest counts of axonal balls as well as the highest incidences. It is recommended that in cases of DAI, these three regions of the brain should be examined most profitably with neurofilament immunostaining supplemented with a myelin stain.

Adolescent↗
PubMed2000

Content change of neurofilament protein subunits in experimental brain diffuse axonal injury by lateral head rotation.

OBJECTIVE: To explore the content change of neurofilament (NF) protein subunits in the experimental brain diffuse axonal injury (DAI) by lateral head rotation. METHODS: Twenty-four Sprague Dawley (SD) rats were equally divided into three injury groups (2 h, 12 h, and 24 h post injury) and one control group. The models of DAI were made in the injury groups by lateral head rotation. Western blotting technique was used to measure the content of NF68 (a kind of NF protein subunit) in the brainstem tissues among all the injured and control rats. The NF68 immunohistochemical staining was used in another six SD rats in order to observe the morphological changes in DAI. RESULTS: The NF68 content in the brainstem tended to decrease at 2 h post injury, decreased significantly at 12 h and continued its decrease at 24 h. NF56 and NF52, as the breakdown products of NF68, had a tendency to increase at 2-12 h after the injury, and amounted to a significantly higher level at 24 h. Microscopically, there were a lot of swelling neuronal axons in the ventral part of the medullar oblongata at 2 h after the injury. Some axons were disconnected, and axonal retraction balls formed on their proximal end. CONCLUSIONS: There is an occurrence of phosphorolysis within the brainstem in DAI by lateral head rotation. These reactions cause the breakdown of NF68, which results in the decrease of NF68 in content. It suggests that the breakdown of neurofilament protein subunits is an important reason for structur al destroy of neurofilaments in DAI.

Journal Article↗
PubMed1993

Ubiquitin marks the reactive swellings of diffuse axonal injury.

Ubiquitin is a protein that targets proteins for non-lysosomal degradation. It has been found to be present in a number of inclusions characteristic of neurodegenerative diseases. Using the fluid percussion model of closed head injury in the cat, a well-established model of diffuse axonal injury (DAI), we now report that the reactive axonal swellings and the retraction balls produced in this model stain positively with anti-ubiquitin immunohistochemistry. Furthermore, the affected axons become ubiquitin positive quickly (within the first 6 h after injury). Anti-ubiquitin immunohistochemistry compares well with the recently reported ability of antibodies to low molecular weight neurofilament proteins to demonstrate reactive axonal change in DAI, and it could provide additional clues to the pathogenesis of axonal transection.

Animals↗