Evaluation of neurogranin levels in a rat model of diffuse axonal injury.

Diffuse axonal injury (DAI), one of the most common and devastating type of traumatic brain injury, is the result of the shear force on axons due to severe rotational acceleration and deceleration. Neurogranin (NRGN) is a postsynaptic protein secreted by excitatory neurons, and synaptic dysfunction can alter extracellular NRGN levels. In this study, we examined NRGN levels in serum and cerebrospinal fluid (CSF) after experimental DAI in terms of their diagnostic value. Experimental DAI was induced using the Marmarou technique in male Wistar albino rats. Serum and CSF NRGN levels of the sham group, one­hour, six­hour, 24­hour, and 72­hour post­DAI groups were measured by ELISA method. DAI was verified by staining with hematoxylin­eosin and ß­amyloid precursor protein in the rat brain samples. While no histopathological and immunohistochemical changes were observed in the early hours of the post­DAI groups, the staining of the ß­APP visibly increased over time, with positivity being most frequent and intense in the 72­hour group. It was found that serum NRGN levels were significantly lower in the 6­hour group than in the sham group. The serum NRGN levels in the 24­hour group were significantly higher than those in the sham group. This study showed a dichotomy of post­DAI serum NRGN levels in consecutive time periods. NRGN levels in CSF were higher in the one­hour group than in the sham group and returned to baseline by 72 hours, although not significantly. Our study provides an impression of serum and CSF NRGN levels in a rat DAI model in consecutive time periods. Further studies are needed to understand the diagnostic value of NRGN.

Annexin A1 conveys neuroprotective function via inhibiting oxidative stress in diffuse axonal injury of rats.

Diffuse axonal injury (DAI) is a critical pathological facet of traumatic brain injury (TBI). Oxidative stress plays a significant role in the progress of DAI. Annexin A1 (AnxA1) has been demonstrated to benefit from recovery of neurofunctional outcomes after TBI. However, whether AnxA1 exhibits neuronal protective function by modulating oxidative stress in DAI remains unknown. Expression of AnxA1 was evaluated via real-time PCR and western blotting in rat brainstem after DAI. The neurological effect of AnxA1 following DAI through quantification of modified neurologic severity score (mNSS) was compared between wild-type and AnxA1-knockout rats. Brain edema and neuronal apoptosis, as well as expression of oxidative factors and inflammatory cytokines, were analyzed between wild-type and AnxA1 deficiency rats after DAI. Furthermore, mNSS, oxidative and inflammatory cytokines were assayed after timely administration of recombinant AnxA1 for DAI rats. In the brainstem of DAI, the expression of AnxA1 remarkably increased. Ablation of AnxA1 increased the mNSS score and brain water content of rats after DAI. Neuron apoptosis in the brainstem after DAI was exaggerated by AnxA1 deficiency. In addition, AnxA1 deficiency significantly upregulated the level of oxidative and inflammatory factors in the brainstem of DAI rats. Moreover, mNSS decreased by AnxA1 treatment in rats following DAI. Expression of oxidative and inflammatory molecules in rat brainstem subjected to DAI inhibited by AnxA1 administration. AnxA1 exhibited neuronal protective function in the progression of DAI mainly dependent on suppressing oxidative stress and inflammation.

Diffuse axonal injury on magnetic resonance imaging and its relation to neurological outcomes in pediatric traumatic brain injury.

OBJECTIVE: Diffuse axonal injury (DAI), a frequent consequence of pediatric traumatic brain injury (TBI), presents challenges in predicting long-term recovery. This study investigates the relationship between the severity of DAI and neurological outcomes in children. METHODS: We conducted a retrospective analysis of 51 pediatric TBI patients diagnosed with DAI using Adam's classification. Neurological function was assessed at 2, 3, and 6 weeks, and 12 months post-injury using the Pediatric Glasgow Outcome Scale-Extended (PGOSE). RESULTS: PGOSE scores significantly improved over time across all DAI grades, suggesting substantial recovery potential even in initially severe cases. Despite indicating extensive injury, patients with DAI grades II and III demonstrated significant improvement, achieving a good recovery by 12 months. Although the initial Glasgow Coma Scale (GCS) score did not show a statistically significant association with long-term outcomes in our limited sample, these findings suggest that the severity of DAI alone may not fully predict eventual recovery. CONCLUSIONS: Our study highlights the potential for significant neurological recovery in pediatric patients with DAI, emphasizing the importance of long-term follow-up and individualized rehabilitation programs. Further research with larger cohorts and extended follow-up periods is crucial to refine our understanding of the complex relationships between DAI severity, injury mechanisms, and long-term neurological outcomes in children.

Molecular biomarkers of diffuse axonal injury: recent advances and future perspectives.

INTRODUCTION: Diffuse axonal injury (DAI), with high mortality and morbidity both in children and adults, is one of the most severe pathological consequences of traumatic brain injury. Currently, clinical diagnosis, disease assessment, disability identification, and postmortem diagnosis of DAI is mainly limited by the absent of specific molecular biomarkers. AREAS COVERED: In this review, we first introduce the pathophysiology of DAI, summarized the reported biomarkers in previous animal and human studies, and then the molecular biomarkers such as ß-Amyloid precursor protein, neurofilaments, S-100ß, myelin basic protein, tau protein, neuron-specific enolase, Peripherin and Hemopexin for DAI diagnosis is summarized. Finally, we put forward valuable views on the future research direction of diagnostic biomarkers of DAI. EXPERT OPINION: In recent years, the advanced technology has ultimately changed the research of DAI, and the numbers of potential molecular biomarkers was introduced in related studies. We summarized the latest updated information in such studies to provide references for future research and explore the potential pathophysiological mechanism on diffuse axonal injury.

Hyperglycemia disrupted the integrity of the blood-brain barrier following diffuse axonal injury through the sEH/NF-κB pathway.

OBJECTIVES: We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced-disruption of blood-brain barrier (BBB) integrity after diffuse axonal injury (DAI). METHODS: Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium-binding adapter molecule-1, ß-amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. The permeability of blood-brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the nuclear transcription factor kappa B (NF-κB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol-12-myristate-13-acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme-linked immunosorbent assay. RESULTS: Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF-κB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF-κB pathway abrogated the protective effects of TPPU on BBB integrity in vitro. CONCLUSIONS: sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF-κB pathway.

Radiomics Enhances Diagnostic and Prognostic Value of Diffusion Kurtosis Imaging in Diffuse Axonal Injury.

The aim of our study was to investigate the potential of advanced radiomics in analyzing diffusion kurtosis MRI (DKI) to increase the informativeness of DKI in diffuse axonal injury (DAI). We hypothesized that DKI radiomic features could be used to detect microstructural brain injury and predict outcomes in DAI. The study enrolled 31 patients with DAI (mean age 31.48 ± 11.10 years, 8 (25.8%) female) and 12 healthy volunteers (mean age 33.67 ± 11.06 years, 4 (33.3%) female). A total of 342,300 radiomic features were calculated (2282 features per each combination of 10 parametric DKI maps with 15 ROIs). Our results showed that several radiomic features were capable of distinguishing between healthy and injured brain tissue and accurately predicting outcomes with an accuracy of over 0.9. Advanced DKI radiomic features show high diagnostic and prognostic potential in DAI and may outperform average ROI values in DKI maps.

Disrupted functional connectivity of the striatum in patients with diffuse axonal injury: a resting-state functional MRI study.

Diffuse axonal injury (DAI) disrupts the integrity of white matter microstructure and affects brain functional connectivity, resulting in persistent cognitive, behavioral and affective deficits. Mounting evidence suggests that altered cortical-subcortical connectivity is a major contributor to cognitive dysfunction. The functional integrity of the striatum is particularly vulnerable to DAI, but has received less attention. This study aimed to investigate the alteration patterns of striatal subdivision functional connectivity. Twenty-six patients with DAI and 27 healthy controls underwent resting-state fMRI scans on a 3.0 T scanner. We assessed striatal subdivision functional connectivity using a seed-based analysis in DAI. Furthermore, a partial correlation was used to measure its clinical association. Compared to controls, patients with DAI showed decreased functional connectivity between the right inferior ventral striatum and right inferior frontal gyrus, as well as the right inferior parietal lobule, between the left inferior ventral striatum and right inferior frontal gyrus, between the right superior ventral striatum and bilateral cerebellar posterior lobe, between the bilateral dorsal caudal putamen and right anterior cingulate gyrus, and between the right dorsal caudal putamen and right inferior parietal lobule. Moreover, decreased functional connectivity was observed between the left dorsal caudate and the right cerebellar posterior lobe, while increased functional connectivity was found between the left dorsal caudate and right inferior parietal lobule. Correlation analyses showed that regions with functional connectivity differences in the DAI group correlated with multiple clinical scoring scales, including cognition, motor function, agitated behavior, and anxiety disorders. These findings suggest that abnormalities in cortico-striatal and cerebellar-striatal functional connectivity are observed in patients with DAI, enriching our understanding of the neuropathological mechanisms of post-injury cognitive disorders and providing potential neuroimaging markers for the diagnosis and treatment of DAI.

The Relationship Between Cortical Morphological and Functional Topological Properties and Clinical Manifestations in Patients with Posttraumatic Diffuse Axonal Injury: An Individual Brain Network Study.

To evaluate the altered network topological properties and their clinical relevance in patients with posttraumatic diffuse axonal injury (DAI). Forty-seven participants were recruited in this study, underwent 3D T1-weighted and resting-state functional MRI, and had single-subject morphological brain networks (MBNs) constructed by Kullback-Leibler divergence and functional brain networks (FBNs) constructed by Pearson correlation measurement interregional similarity. The global and regional properties were analyzed and compared using graph theory and network-based statistics (NBS), and the relationship with clinical manifestations was assessed. Compared with those of the healthy subjects, MBNs of patients with DAI showed a higher path length ([Formula: see text]: P = 0.021, [Formula: see text]: P = 0.011), lower clustering ([Formula: see text]: P = 0.002) and less small-worldness ([Formula: see text]: P = 0.002), but there was no significant difference in the global properties of FBNs (P: 0.161-0.216). For nodal properties of MBNs and FBNs, several regions showed significant differences between patients with DAI and healthy controls (HCs) (P < 0.05, FDR corrected). NBS analysis revealed that MBNs have more altered morphological connections in the frontal parietal control network and interhemispheric connections (P < 0.05). DAI-related global or nodal properties of MBNs were correlated with physical disability or dyscognition (P < 0.05/7, with Bonferroni correction), and the alteration of functional topology properties mediates this relationship. Our results suggested that disrupted morphological topology properties, which are mediated by FBNs and correlated with clinical manifestations of DAI, play a critical role in the short-term and medium-term phases after trauma.

Mechanical mechanism and indicator of diffuse axonal injury under blast-type acceleration.

Diffuse axonal injury (DAI) caused by acceleration is one of the most prominent forms of blast-induced Traumatic Brain Injury. However, the mechanical mechanism and indicator of axonal deformation-induced injury under blast-type acceleration with high peak and short duration are unclear. This study constructed a multilayer head model that can reflect the response characteristics of translational and rotational acceleration (the peak time of which is within 0.5 ms). Based on von Mises stress, axonal strain and axonal strain rate indicators, the physical process of axonal injury is studied, and the vulnerable area under blast-type acceleration load is given. In the short term (within 1.75 ms), dominated by sagittal rotational acceleration peaks, the constraint of falx and tentorium rapidly imposes the inertial load on the brain tissue, resulting in a high-rate deformation of axons (axonal strain rate of which exceed 100 s-1). For a long term (after 1.75 ms), fixed-point rotation of the brain following the head causes excessive distortion of brain tissue (von Mises stress of which exceeds 15 kPa), resulting in a large axonal stretch strain where the main axonal orientation coincides with the principal strain direction. It is found that the axonal strain rate can better indicate the pathological axonal injury area and coincides with external inertial loading in the risk areas, which suggests that DAI under blast-type acceleration overload is mainly caused by the rapid axonal deformation instead of by the excessive axonal strain. The research in this paper helps understand and diagnose blast-induced DAI.

Modification of the Marmarou and Foda model of diffuse axonal injury (DAI) improves percentage survival of rats at 24 h and increases the amount of DAI identified.

More than two decades ago, Marmarou published a valid model for producing diffuse axonal injury (DAI) in rats. Since then, both mild and severe injuries have been obtained by researchers using the original method and a weight of 450 g. However, the diffuse brain injuries produced in rats were only similar to those seen in humans when the rats sustained severe brain injuries. In these cases, rat mortality in the original article was around 50%, and the cause of death was prolonged apnea post-impact. Rat survival after impact is critical for studying the progression of DAI. In order to explain the cause of death in human victims with cranial trauma who do not show gross brain injury, testing for the presence of DAI is essential. Thus, in order to minimize local and cervical injuries to increase rat survival, attention should be paid to the following aspects: a wider head protector disc should be used, the head of the rat should be elevated at the time of impact, and the foam bed should be soft enough to allow the movement caused by acceleration. With our modified method, rat survival increased by 30% compared to the original model (80% versus 50%). Moreover, 85.7% of rats demonstrated DAI after 24 h of survival. With these modifications, injuries appear in the same locations as in humans; thus, the method is suitable for the study of traumatic DAI in humans.

[Primary injuries of corpus callosum vessels in craniocerebral injuries]. / Pervichnye povrezhdeniya sosudov mozolistogo tela pri cherepno-mozgovoi travme.

The aim of the scientific work is to establish morphological characteristics of hemorrhages in the corpus callosum as a marker of primary vascular injuries in diffuse axonal injury (DAI) in relation to the goals and objectives of forensic examination. Changes in the structures of corpus callosum were analyzed in 45 corpses of persons with traumatic brain injury who died in hospital from DAI diagnosed according to clinical and instrumental data within 24 hours after the trauma. The changes were characterized by rectic hemorrhages (haemorrhagia per rhexin) in combination with successively developing vascular, tissue, and cellular post-traumatic reactions. These changes were not observed in the control group. The following morphological characteristics of hemorrhages were established: small focal, elongated, clearly contoured hemorrhages of different sizes, up to 4 mm long, up to 0.8 mm wide, unidirectional at an angle from the lower to upper surface of the sagittal corpus callosum section, at least three, grouped in limited areas sized up to 1.5 × 1.0 cm without clear borders. The detected hemorrhages and the course of changes give reason to consider them the result of primary traumatic effects, making them a diagnostic marker of DAI.

Ballooned neurons in semi-recent severe traumatic brain injury.

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects.

A model for estimating the brainstem volume in normal healthy individuals and its application to diffuse axonal injury patients.

Diffuse axonal injury (DAI) is a subtype of traumatic brain injury that causes acute-phase consciousness disorders and widespread chronic-phase brain atrophy. Considering the importance of brainstem damage in DAI, a valid method for evaluating brainstem volume is required. We obtained volume measurements from 182 healthy adults by analyzing T1-weighted magnetic resonance images, and created an age-/sex-/intracranial volume-based quantitative model to estimate the normal healthy volume of the brainstem and cerebrum. We then applied this model to the volume measurements of 22 DAI patients, most of whom were in the long-term chronic phase and had no gross focal injury, to estimate the percentage difference in volume from the expected normal healthy volume in different brain regions, and investigated its association with the duration of posttraumatic amnesia (which is an early marker of injury severity). The average loss of the whole brainstem was 13.9%. Moreover, the percentage loss of the whole brainstem, and particularly of the pons and midbrain, was significantly negatively correlated with the duration of posttraumatic amnesia. Our findings suggest that injury severity, as denoted by the duration of posttraumatic amnesia, is among the factors affecting the chronic-phase brainstem volume in patients with DAI.

Hyperglycemia Aggravates Blood-Brain Barrier Disruption Following Diffuse Axonal Injury by Increasing the Levels of Inflammatory Mediators through the PPARγ/Caveolin-1/TLR4 Pathway.

Hyperglycemia aggravates brain damage after diffuse axonal injury (DAI), but the underlying mechanisms are not fully defined. In this study, we aimed to investigate a possible role for hyperglycemia in the disruption of blood-brain barrier (BBB) integrity in a rat model of DAI and the underlying mechanisms. Accordingly, 50% glucose was intraperitoneally injected after DAI to establish the hyperglycemia model. Hyperglycemia treatment aggravated neurological impairment and axonal injury, increased cell apoptosis and glial activation, and promoted the release of inflammatory factors, including TNF-α, IL-1ß, and IL-6. It also exacerbated BBB disruption and decreased the expression of tight junction-associated proteins, including ZO-1, claudin-5, and occludin-1, whereas the PPARγ agonist rosiglitazone (RSG) had the opposite effects. An in vitro BBB model was established by a monolayer of human microvascular endothelial cells (HBMECs). Hyperglycemia induction worsened the loss of BBB integrity induced by oxygen and glucose deprivation (OGD) by increasing the release of inflammatory factors and decreasing the expression of tight junction-associated proteins. Hyperglycemia further reduced the expression of PPARγ and caveolin-1, which significantly decreased after DAI and OGD. Hyperglycemia also further increased the expression of toll-like receptor 4 (TLR4), which significantly increased after OGD. Subsequently, the PPARγ agonist RSG increased caveolin-1 expression and decreased TLR4 expression and inflammatory factor levels. In contrast, caveolin-1 siRNA abrogated the protective effects of RSG in the in vitro BBB model of hyperglycemia by increasing TLR4 and Myd88 expression and the levels of inflammatory factors, including TNF-α, IL-1ß, and IL-6. Collectively, we demonstrated that hyperglycemia was involved in mediating secondary injury after DAI by disrupting BBB integrity by inducing inflammation through the PPARγ/caveolin-1/TLR4 pathway.

Role of integrin and its potential as a novel postmortem biomarker in traumatic axonal injury.

Traumatic axonal injury (TAI) accounts for a large proportion of the mortality of traumatic brain injury (TBI). The diagnosis of TAI is currently of limited use for medicolegal purposes. It is known that axons in TAI are diffusely damaged by secondary processes other than direct head injury. However, the physiopathological mechanism of TAI is still elusive. The present study used RGD peptide, an antagonist of the mechanotransduction protein integrin, to explore the role of integrin-transmitted mechanical signalling in the pathogenesis of rat TAI. The rats were subjected to a linearly accelerating load, and changes in beta-amyloid precursor protein (ß-APP) expression, skeleton ultrastructure, skeleton protein neurofilament light (NF-L), and α-tubulin in the brainstem were observed, indicating that RGD could relieve the severity of axonal injury in TAI rats. In addition, the expression of ß-integrin was stronger and centralized in the brainstem of the deceased died from TAI compared to other nonviolent causes. This study examined the pathophysiology and biomechanics of TAI and assessed the role of integrin in the injury of microtubules and neurofilaments in TAI. Thus, we propose that integrin-mediated cytoskeletal injury plays an important role in TAI and that integrin has the potential as a biomarker for TAI.

[Morphological markers of pathophysiological changes in the neuronal processes in the acute post-traumatic period of diffuse axonal injury]. / Morfologicheskie markery patofiziologicheskikh izmenenii otrostkov neironov v ostrom posttravmaticheskom periode diffuznogo aksonal'nogo povrezhdeniya mozga.

The purpose of the study was to establish morphological markers of pathophysiological changes in the neuronal processes of in the acute (up to 36 hours) post-traumatic period of diffuse axonal injury (DAI) for the purposes of expert practice. Histological examination of the body of corpus callosum of the corpses of 66 persons dead from DAI and of 25 persons dead from various non-violent and violent causes, excluding head trauma, was performed (control group). Morphological markers of specific pathophysiological changes in the neuronal process were established by light microscopy with the use of immunohistochemical examination in acute period DAI. Uneven contours of the processes suggested displacement of cytoskeletal elements, areas of vacuolization of the cytoplasm of the processes suggested violation of intracellular transport caused by a change of permeability with preserved integrity of the process shell without mechanical separation of the process, uneven thickness (3.9 ± 1.6 µm) of the processes, varicose and cone-shaped thickening of them was a manifestation of focal edema of the neuronal process and compression of the cytoskeleton as a result of ion-enzymatic disorders, uneven coloration, areas of fragmentary compaction of neurofilaments indicated the zones of deformation and compression of the cytoskeleton, zones of granular-lumpy decay and fibrillolysis of neurofilaments indicated destruction of the cytoskeleton. Changes in the neuronal processes are a manifestation of a polyethological general pathological process and are not a differential diagnostic criterion of DAI.

Prognostic Significance of Magnetic Resonance Imaging in Detecting Diffuse Axonal Injuries: Analysis of Outcomes and Review of Literature.

Background: Diffuse axonal injury (DAI) is the brain injury characterized by extensive lesions in the white matter tracts over a widespread area. DAI is one of the most common and devastating types of traumatic brain injury and a major cause of unconsciousness and persistent vegetative state after head trauma. It occurs in about half of all cases with severe head trauma. Objective: This study was undertaken to evaluate the prognostic significance of magnetic resonance imaging (MRI) in detecting DAI and to determine which clinical factors provide prognostic information in patients with traumatic brain injuries. Materials and Methods: This prospective study was conducted in a tertiary care hospital between April 2017 to May 2019 on 52 patients admitted to the hospital with severe traumatic injuries of the head and clinical diagnosis of DAI. The clinical outcomes and findings of Thecomputerized tomography (CT)/magnetic resonance imaging (MRI) of the brain were assessed at 1 month, 3 months, 6 months, and 1 year on the basis of improvement in Glasgow Coma Scale (GCS), the time required to consciousness, and the duration of hospital stay. The patients were classified into three groups according to the MRI grading classification proposed by Adams. The outcomes at the 6 month follow-up time were dichotomized as non recovered (Glasgow Outcome Scale (GOS) score 1 or 2) or recovered (GOS score 3-5).The following factors were evaluated in relation to outcome: age, admission GCS score, the motor component of the GCS examination at admission and at 24 hours post admission, brainstem injury based on T2-weighted and gradient echo MRI sequences, presence of bilateral brainstem injuries, presence of DAIin the brainstem and the supra tentorial compartment (including the cortex, basal ganglia, and corpus callosum) on both CT and MRI, cerebral contusions, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and intraventricular hemorrhage. The statistical analysis was performed with x2 between various stages and between patients with and without hemorrhagic DAI. A separate analysis with x2 and Yates' correction was performed after grouping the patients with good recovery and moderate disability against patients with severe disability and vegetative state. Results: The correlation of patients GCS on admission, after 24 hours, and at discharge is statistically significant P < 0.001. Correlation among mean hospital stay in Grade I DAI, Grade II DAI, and Grade III DAI wass statistically significant (f = 70.22, P < 0.001). Correlation among mean time required for consciousness in Grade I DAI, Grade II DAI, and Grade III DAI was statistically significant (f = 181.92, P < 0.001). Based on anatomical location within the brainstem, the poorest outcomes occurred with injury to the medulla- with a 100% mortality rate. Poor outcomes were also associated with any injury to the pons. There was a significant correlation among brainstem injuries that crossed the midline, the motor component of the GCS examination, performed 24 hours after admission and at outcome. The median time to MRI was 1 day (range 0-35 days) among all, but 4 patients underwent MRI within 7 days after admission. Patients who did not recover underwent MRI at an average of 0.8 days after admission, whereas those who recovered underwent MRI at an average of 4.2 days after admission (P = 0.52). To determine if the time from admission to MRI had an influence on results, comparison was made between T2 and patient outcomes in relation to the interval between admission and MRI. Statistical analysis in the group of patients with different DAI stages showed a significant difference (P = 0.013). A statistically significant difference was also found between patients with hemorrhagic and non hemorrhagic DAI (P = 0.004). Conclusion: The current study showed a correlation between the mean time interval to recovery of consciousness in patients with DAI and the severity of injury grading on MRI. Hospital stay required for Grade I DAI was 2-3 weeks, for Grade II DAI was 3-4 weeks, and for Grade III DAI was 7-8 weeks. Apart from the well-known role of the Glasgow Coma Scale (GCS) in the prognosis of the outcome of patients with closed head injury, the presence of hemorrhage in DAI-type lesions and the association with traumatic space occupying lesions are additional poor prognostic signs established in this study. The analysis of outcomes were done for patients admitted with DAI and the current study established that poor outcomes were consistently seen in patients with brainstem injuries and poor results on 24-hour post admission GCS motor examinations.