An axonal strain injury criterion for traumatic brain injury

Computational models are often used as tools to study traumatic brain injury. The fidelity of such models depends on the incorporation of an appropriate level of structural detail, the accurate representation of the material behavior, and the use of an appropriate measure of injury. In this study, an axonal strain injury criterion is used to estimate the probability of diffuse axonal injury (DAI), which accounts for a large percentage of deaths due to brain trauma and is characterized by damage to neural axons in the deep white matter regions of the brain. We present an analytical and computational model that treats the white matter as an anisotropic, hyperelastic material. Diffusion tensor imaging is used to incorporate the structural orientation of the neural axons into the model. It is shown that the degree of injury that is predicted in a computational model of DAI is highly dependent on the incorporation of the axonal orientation information and the inclusion of anisotropy into the constitutive model for white matter.     

Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury

Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. TBI severity classification, based on the hospital admission Glasgow Coma Scale (GCS) score, ranges from mild (GCS 13–15) and moderate (GCS 9–12) to severe (GCS ≤ 8). The GCS reflects the risk of dying from TBI, which is low after mild (∼1%), intermediate after moderate (up to 15%) and high (up to 40%) after severe TBI. Intracranial damage can be focal, such as epidural and subdural haematomas and parenchymal contusions, or diffuse, for example traumatic axonal injury and diffuse cerebral oedema, although this distinction is somewhat arbitrary. Study of the cellular and molecular post-traumatic processes is essential for the understanding of TBI pathophysiology but even more to find therapeutic targets for the development of neuroprotective drugs to be eventually used in human beings. To date, studies in vitro and in vivo, mainly in animals but also in human beings, are unravelling the pathological TBI mechanisms at high pace. Nevertheless, TBI pathophysiology is all but completely elucidated. Neuroprotective treatment studies in human beings have been disappointing thus far and have not resulted in commonly accepted drugs. This review presents an overview on the clinical aspects and the pathophysiology of focal and diffuse TBI, and it highlights several acknowledged important events that occur on molecular and cellular level after TBI.     

Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury

Background  

Memory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions.     

外伤性急性弥漫性脑肿胀的临床分析

目的:探讨外伤性急性弥漫性脑肿胀的诊断与治疗.方法:回顾性分析颅脑创伤后脑肿胀患者52例的临床资料.结果:52例中完全恢复16例,生活基本自理者11例,重残6例,植物生存3例,死亡16例.入院格拉斯哥昏迷评分(GCS)计分3～5分(瞳孔均散大)27例,预后良好9例,预后不良18例;GOS计分6～8分18例,预后良好12例,预后不良6例;GCS计分9～12分7例,预后良好5例,预后不良2例.结论:急性弥漫性脑肿胀的死亡率高,预后差,应积极综合治疗.     

Serum metabolomic markers for traumatic brain injury: a mouse model

Introduction

Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.

Objectives

Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.

Methods

A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.

Results

Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.

Conclusion

Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.

     

New mechanics of traumatic brain injury

The prediction and prevention of traumatic brain injury is a very important aspect of preventive medical science. This paper proposes a new coupled loading-rate hypothesis for the traumatic brain injury (TBI), which states that the main cause of the TBI is an external Euclidean jolt, or SE(3)-jolt, an impulsive loading that strikes the head in several coupled degrees-of-freedom simultaneously. To show this, based on the previously defined covariant force law, we formulate the coupled Newton–Euler dynamics of brain’s micro-motions within the cerebrospinal fluid and derive from it the coupled SE(3)-jolt dynamics. The SE(3)-jolt is a cause of the TBI in two forms of brain’s rapid discontinuous deformations: translational dislocations and rotational disclinations. Brain’s dislocations and disclinations, caused by the SE(3)-jolt, are described using the Cosserat multipolar viscoelastic continuum brain model.

清醒小鼠严重颅脑闭合性撞击伤模型的建立

目的-建立一种清醒小鼠严重颅脑闭合性撞击伤模型, 模拟交通事故和战伤中的清醒致伤过程, 为相关研究创造新的动物模型基础。方法-将雄性KM小鼠头戴钢盔后清醒固定, 用BIM III型小型多功能动物撞击机击打, 致伤后2 h、8 h、24 h、48 h、72 h、120 h、1 w、2 w进行神经行为学评分、运动功能评分、死亡小鼠脑组织和肺组织水含量、死亡率、病理切片和电镜观察。结果-致伤后 48 h内致伤组运动功能评分、神经行为学评分明显低于对照组 (P<0 05); 致伤后死亡率高, 各组死亡小鼠脑组织水含量无明显差异, 但致伤组肺组织水含量明显高于对照组 (P <0 05); 病理切片和电镜检查显示, 致伤后脑组织细胞肿胀、坏死。结论-基本成功建立了模拟交通事故和战伤的清醒小鼠严重颅脑闭合性撞击伤模型。     

Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury

Background  

We investigated the neuroprotective properties of levosimendan, a novel inodilator, in an in vitro model of traumatic brain injury.     

Progesterone protects mitochondrial function in a rat model of pediatric traumatic brain injury

Journal of Bioenergetics and Biomembranes - Progesterone has been studied extensively in preclinical models of adult traumatic brain injury (TBI), and has advanced to clinical trials in adults with...     

Modulation of autophagy in traumatic brain injury

Traumatic brain injury (TBI) is defined as a traumatically induced structural injury or physiological disruption of brain function as a result of external forces, leading to adult disability and death. A growing body of evidence reveals that alterations in autophagy-related proteins exist extensively in both experimentally and clinically after TBI. Of note, the autophagy pathway plays an essential role in pathophysiological processes, such as oxidative stress, inflammatory response, and apoptosis, thus contributing to neurological properties of TBI. With this in mind, this review summarizes a comprehensive overview on the beneficial and detrimental effects of autophagy in pathophysiological conditions and how these activities are linked to the pathogenesis of TBI. Moreover, the relationship between oxidative stress, inflammation, apoptosis, and autophagy occur TBI. Ultimately, multiple compounds and various drugs targeting the autophagy pathway are well described in TBI. Therefore, autophagy flux represents a potential clinical therapeutic value for the treatment of TBI and its complications.     

A proposed injury threshold for mild traumatic brain injury

Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanisms, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four head-to-head field collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of mild traumatic brain injury (MTBI). Predictions indicated that the shear stress around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level.     

Acoustic thermometry of the patient brain with traumatic brain injury

Non-invasive deep brain acoustic thermometry is carried out for two patients at Burdenko Neurosurgery Institute. This method is based on the measurements of the own thermal acoustic radiation of the investigated object. These two patients have got the brain injury. Some of their skull bones are absent. Infrared thermometry was also used to measure the surface temperature of the forehead skin. On the basis of the experimental data the temperatures deep within the brain were reconstructed. The values for the two patients are equal to 37.3 ± 0.7 and 37.0 ± 0.3°C.     

The gut reaction to traumatic brain injury

Traumatic brain injury (TBI) is a complex disorder that affects millions of people worldwide. The complexity of TBI partly stems from the fact that injuries to the brain instigate non-neurological injuries to other organs such as the intestine. Additionally, genetic variation is thought to play a large role in determining the nature and severity of non-neurological injuries. We recently reported that TBI in flies, as in humans, increases permeability of the intestinal epithelial barrier resulting in hyperglycemia and a higher risk of death. Furthermore, we demonstrated that genetic variation in flies is also pertinent to the complexity of non-neurological injuries following TBI. The goals of this review are to place our findings in the context of what is known about TBI-induced intestinal permeability from studies of TBI patients and rodent TBI models and to draw attention to how studies of the fly TBI model can provide unique insights that may facilitate diagnosis and treatment of TBI.     

Extracellular N-acetylaspartate depletion in traumatic brain injury

N-Acetylaspartate (NAA) is almost exclusively localized in neurons in the adult brain and is present in high concentration in the CNS. It can be measured by proton magnetic resonance spectroscopy and is seen as a marker of neuronal damage and death. NMR spectroscopy and animal models have shown NAA depletion to occur in various types of chronic and acute brain injury. We investigated 19 patients with traumatic brain injury (TBI). Microdialysis was utilized to recover NAA, lactate, pyruvate, glycerol and glutamate, at 12-h intervals. These markers were correlated with survival and a 6-month Glasgow Outcome Score. Eleven patients died and eight survived. A linear mixed model analysis showed a significant effect of outcome and of the interaction between time of injury and outcome on NAA levels (p = 0.009 and p = 0.004, respectively). Overall, extracellular NAA was 34% lower in non-survivors. A significant non-recoverable fall was observed in this group from day 4 onwards, with a concomitant rise in lactate-pyruvate ratio and glycerol. These results suggest that mitochondrial dysfunction is a significant contributor to poor outcome following TBI and propose extracellular NAA as a potential marker for monitoring interventions aimed at preserving mitochondrial function.     

Proteomic identification of biomarkers of traumatic brain injury

Traumatic brain injury (TBI) is a major national health problem without a US Food and Drug Administration-approved therapy. This review summarizes the importance of discovering relevant TBI protein biomarkers and presents logical rationale that neuroproteomic technologies are uniquely suited for the discovery of otherwise unnoticed TBI biomarkers. It highlights that one must make careful decisions when choosing which paradigm (human vs. animal models) and which biologic samples to use for such proteomic studies. It further outlines some of the desirable attributes of an ideal TBI biomarker and discusses how biomarkers discovered proteomically are complementary to those identified by traditional approaches. Lastly, the most important sequela of any proteomically identified TBI biomarker is validation in preclinical or clinical samples.