Gharahi Hamidreza, Garimella Harsha T, Chen Zhijian J, Gupta Raj K, Przekwas Andrzej
Biomedical and Data Sciences Division, CFD Research Corporation, Huntsville, AL, United States.
Department of Defense Blast Injury Research Program Coordinating Office, U.S. Army Medical Research and Development Command, Fort Detrick, MD, United States.
Front Cell Neurosci. 2023 Feb 6;17:1007062. doi: 10.3389/fncel.2023.1007062. eCollection 2023.
Blast induced Traumatic Brain Injury (bTBI) has become a signature casualty of military operations. Recently, military medics observed neurocognitive deficits in servicemen exposed to repeated low level blast (LLB) waves during military heavy weapons training. In spite of significant clinical and preclinical TBI research, current understanding of injury mechanisms and short- and long-term outcomes is limited. Mathematical models of bTBI biomechanics and mechanobiology of sensitive neuro-structures such as synapses may help in better understanding of injury mechanisms and in the development of improved diagnostics and neuroprotective strategies.
In this work, we formulated a model of a single synaptic structure integrating the dynamics of the synaptic cell adhesion molecules (CAMs) with the deformation mechanics of the synaptic cleft. The model can resolve time scales ranging from milliseconds during the hyperacute phase of mechanical loading to minutes-hours acute/chronic phase of injury progression/repair. The model was used to simulate the synaptic injury responses caused by repeated blast loads.
Our simulations demonstrated the importance of the number of exposures compared to the duration of recovery period between repeated loads on the synaptic injury responses. The paper recognizes current limitations of the model and identifies potential improvements.
爆炸所致创伤性脑损伤（bTBI）已成为军事行动中的典型伤亡类型。最近，军事医护人员在军事重型武器训练期间观察到，暴露于反复低强度爆炸（LLB）波的军人存在神经认知缺陷。尽管有大量临床和临床前TBI研究，但目前对损伤机制以及短期和长期后果的了解仍然有限。bTBI生物力学和敏感神经结构（如突触）的力学生物学数学模型可能有助于更好地理解损伤机制，并有助于开发改进的诊断方法和神经保护策略。
在这项工作中，我们构建了一个单一突触结构模型，将突触细胞粘附分子（CAMs）的动力学与突触间隙的变形力学相结合。该模型能够解析从机械加载超急性期的毫秒级到损伤进展/修复急性/慢性期的分钟至小时级的时间尺度。该模型用于模拟反复爆炸载荷引起的突触损伤反应。
我们的模拟结果表明，与反复载荷之间的恢复期持续时间相比，暴露次数对突触损伤反应具有重要影响。本文认识到该模型目前的局限性，并确定了潜在的改进方向。
