Moderate Diffuse Axonal Injury Research Articles

Deep learning method to assess brain injury risk

Model-based brain injury criteria can present higher potential to predict injury than global head kinematic parameters. Numerical head injury prediction tools are time consuming and require Finite Element (FE) skilled users. To address these difficulties, a deep learning technique was applied to an existing previously developed brain FE model for which an injury risk curve has been proposed in terms of maximum Von Mises stress to predict moderate diffuse axonal injury. A total of 4492 experimental head impacts coming from experimental helmet testing were considered as input for the analysis. Each input was expressed in terms of three linear accelerations and three angular velocities versus time, when the target metric was the time history Von Mises Stress () curve computed within the brain via the FE analysis. The architecture used for the Deep Learning (DL) model is the U-Net and four models based on it were evaluated. The dataset was split into three datasets dedicated for learning and testing. The quality of the DL models were assessed via the Maximum Absolute Error between FE and DL models computed brain maximum Further, a regression analysis of brain response with both methods was conducted. The results demonstrated that deep learning methods can be applied in the context of brain response estimation when helmet assessment is considered without any FE computation, only by considering the 6 D head kinematic vs time demonstrating that the deep learning approach should be further developed for research and industrial applications.

Serum levels of tau protein increase according to the severity of the injury in DAI rat model.

Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury.DAI was induced in animals using the Marmarou model.After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteenratswereemployedin the present studyand were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury.Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild, P=0.02; mild vs. severe, P=0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.

Experimental and numerical considerations of helmet evaluation under oblique impact

Based on real-world bicycle accident reconstructions and virtual accident simulations, the present study proposes realistic head-impact conditions in terms of oblique impact velocities. Thus, an existing bicycle helmet has been impacted frontally and laterally under oblique impacts with a Hybrid III dummy head fully instrumented for a 6D motion recording. The head acceleration curves were implemented in the Strasbourg University Finite Elements Head Model to assess the brain-injury risk in terms of intracerebral Von-Mises stress. Results of the experimental respectively numerical head response are expressed in terms of maximum linear and rotational accelerations, HIC, and brain-injury risk. Results show maximum linear acceleration of about 152g leading to HIC of 700. The maximum rotational head accelerations ranged from 5 to 12 krad/s², according to the rotation axis. The numerical head-injury risk assessment conducted to a risk of moderate DAI (Diffuse Axonal Injury) in the 27% to 70% range. These results demonstrated that the direction and time evolution of linear and rotational accelerations need to be taken account via the use of model-based head-injury criteria. This study is therefore a demonstrator for novel helmet test method as well as a step for advanced bicycle helmet design.

Myelin Damage in Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is characterized by delayed axonal disconnection. Although the effect of DAI on axonal pathology has been well documented, there is limited information regarding the role of myelin in the pathogenesis of DAI. We used a modified Marmarou method to create a moderate DAI model in adult rat and examined the corpus callosum and brain stem for myelin pathology and dynamic glial responses to DAI. During the first week following DAI, Luxol Fast Blue staining and western blot analysis for MBP showed significant loss of myelin in the corpus callosum and the brain stem. Increased apoptosis of mature oligodendrocyte, as depicted by its marker CC-1, was observed. Conversely, there was an increased number of Olig2-positive cells accompanied by hypertrophic microglia/macrophage and mild reactive astrocytes. Electron microscopy revealed degenerating axons in the corpus callosum and marked myelin abnormalities in the brain stem in the early stage of DAI. Brain stem regions exhibited myelin intrusions or external protrusions with widespread delamination and myelin collapse, leading to degeneration of accompanying axons. Our results show distinct pathologic processes involving axon and myelin between the corpus callosum and the brain stem in DAI. Oligodendrocyte selective vulnerability and subsequent demyelination may contribute to axonal degeneration in the brain stem. Defining the cause of ongoing oligodendrocyte death and promoting myelin regeneration may provide important targets for therapeutic interventions of DAI.

Application of diffusion tensor imaging in prognosis evaluation in patients with moderate and severe diffuse axonal injury

Objective To investigate the application of diffusion tensor imaging (DTI) in evaluating prognosis of patients with moderate and severe diffuse axonal injury (DAI). Methods A prospective cohort study was made on 35 patients with moderate and severe DAI, who were enrolled from June 2013 to December 2015 as study group. There were 21 males and 14 females, with age of (55.1±11.6) years. The Glasgow coma scale (GCS) was (8.2±2.9)points on admission. Moderate DAI was seen in 20 patients and severe DAI in 15 patients. Other 15 healthy volunteers were selected as control group. Fractional anisotropy (FA) was measured by DTI in three areas of interests as follows: the corpus callosum, thalamus, and brainstem areas. Glasgow outcome scale (GOS) was adopted to assess the prognosis of DAI patients at 6 months after the injury. The FA values of the three areas between study group and control group as well as FA values of patients when they were admitted to hospital and 6 months after injury were measured. In this way, the relationship between the FA values of different areas of interests in DAI patients on admission and the prognosis 6 months after injury was analyzed. Results The FA values of the corpus callosum, thalamus and brainstem area in study group were all lower than those in control group (P<0.05). Further, FA values of the corpus callosum, thalamus, brainstem area in severe DAI patients were lower than those of moderate DAI patients (P<0.05). FA values of the corpus callosum, thalamus, brain stem areas in DAI patients at 6 months after injury were lower than those of corresponding areas when DAI patients were admitted to hospital (P<0.05). FA values of the corpus callosum, thalamus and brain stem on admission were significantly positively correlated with GOS at 6 months after injury (P<0.05). Conclusions Lower FA values of the corpus callosum, thalamus and brainstem area in patients with moderate and severe DAI are associated with more severe injury and worse prognosis. DTI scans can be used as a valuable tool to evaluate the prognosis of DAI patients. Key words: Diffuse axonal injury; Diffusion tensor imaging; Prognosis

Histologically Neuroprotective Effect of MgSO4after Moderate Diffuse Axonal Injury in Rats

Objective: Previous studies have shown that blood-ionized magnesium levels decline, associated with the development of histological changes (apoptosis), after traumatic brain injury. Therefore, we have a hypothesis that early magnesium salt treatment may be improving posttraumatic apoptotic change. Methods: Thirty two anesthetized adult Sprague-Dawley rats were injured with a Marmarou's weight-drop device and bloodionized magnesium was checked, prior to and following magnesium administration (MgSO 4 750 μmol/kg. IM). The temporal pattern of apoptosis in rat brain after moderate diffuse axonal injury (mDAI) was characterized using TUNEL histochemistry. Results: After MgSO4 injection at 30 min. posttrauma, animals demonstrated an elevated blood-ionized magnesium concentration reaching a maximum of 2.57±0.03 mg/dL at 2.5 hours after drug administration and apoptotic index was significantly declined by about 45%(54.8±1.7, 51.5±3.2 at 12, 24 h in control group, 24.8±2.6, 20.5±1.4 at 12, 24 h in treated group, p<0.05). Conclusions: These findings suggest that early treatment with MgSO4 is very effective in histological findings following experimental traumatic brain injury in the rat. Clinically, we suspect that an increase in blood-ionized magnesium concentration with administration of magnesium salt may be associated with improvement in neurological and functional outcome.

Apoptotic Change in Response to Magnesium Therapy after Moderate Diffuse Axonal Injury in Rats

The biochemical factors related to moderation of secondary or delayed damage to the central nervous system (CNS) remain undefined. We have recently demonstrated that the weight- drop induced moderate diffuse axonal injury (mDAI) in rats causes a rapid decline in serum ionized magnesium (Mg(2+)) and a significant increase in the amount of serum ionized calcium (Ca(2+)) relative to Mg(2+) (Ca(2+)/ Mg(2+)). For three hours, serum Mg(2+) levels remained significantly depressed at 76% of preinjury values (p < 0.05), but total serum magnesium remained unchanged (tMg, p > 0.05). Head trauma resulted in a small decrease of Ca(2+) (about 10%), but a significant increase in the amount of Ca(2+)/Mg(2+) (mean value in control group: in injured group for 3 hours after trauma =4.65 +/- 0.012 : 5.69 +/- 0.015, p < 0.05) was observed. In order to further investigate the relationship between Mg(2+) and brain injury, the effect of Mg(2+) treatment on posttraumatic histological changes (apoptotic changes) was examined following the weight-drop induced brain injury. At 30 min postinjury, animals treated with MgSO(4) (750 micromol/kg) showed significant improvements of apoptotic changes when compared to the control group (54.8 +/- 1.7, 51.5 +/- 3.2 at 12, 24 h in control group, 24.8 +/- 2.6, 20.5 +/- 1.4 at 12, 24 h in treated group, p < 0.05). The early decline in serum Mg(2+) and the increase in the amount of Ca(2+)/Mg(2+) immediately following brain trauma uncovered by these findings suggest that they may be a critical factor in the development of irreversible tissue injury. If this proves to be the case, treatment with MgSO(4) may be effective in improving histological findings following experimental traumatic brain injury in rats.

Apoptotic change and NOS activity in the experimental animal diffuse axonal injury model.

Although nitric oxide (NO) plays an important role in the pathophysiological process of cerebral ischemia or severe traumatic brain injury, its contribution to the pathogenesis of moderate diffuse axonal injury (mDAI) remains to be clarified. The alterations in nitric oxide synthase (NOS) activity and the histopathological response after mDAI was investigated. Forty anesthetized Sprague-Dawley adult rats were injured with a Marmarou's weight-drop device through a Plexiglas guide tube. These rats were divided into 8 groups (control, 1 hr, 2 hr, 3 hr, 6 hr, 12 hr, 24 hr, 48 hr after trauma). The temporal pattern of apoptosis in the adult rat brain after mDAI was characterized using TUNEL histochemistry. In addition, the cDNA for NOS activity was amplified using RT-PCR. The PCR products were electrophoresed on a 2% agarose gel. eNOS activity was not detected, but nNOS activity was expressed after 3 hr and continuously 48 hr after impact, which was approximately double that of the control group at 12 and 24 hr. Subsequently, there was a decrease in activity after 48 hr. The iNOS activity increased dramatically after 12 hr and was constant for a further 12 hr followed by a dramatic decrease below the level of the control group. Significant apoptotic changes occurred 12 and 24 hr. after insult. nNOS and iNOS activity were affected after moderate diffuse axonal injury in a time-dependent manner and there was a close relation between the apoptotic changes and NOS activity. Although the nNOS activity was expressed early, its activity was not stronger than iNOS, which was expressed later.