Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Ahmedabad, Gandhinagar, Gujarat, India.
Methods Mol Biol. 2024;2761:569-588. doi: 10.1007/978-1-0716-3662-6_38.
Traumatic brain injury (TBI) is one of the foremost causes of disability and death globally. Prerequisites for successful therapy of disabilities associated with TBI involved improved knowledge of the neurobiology of TBI, measurement of quantitative changes in recovery dynamics brought about by therapy, and the translation of quantitative methodologies and techniques that were successful in tracking recovery in preclinical models to human TBI. Frequently used animal models of TBI in research and development include controlled cortical impact, fluid percussion injury, blast injury, penetrating blast brain injury, and weight-drop impact acceleration models. Preclinical models of TBI benefit from controlled injury settings and the best prospects for biometric quantification of injury and therapy-induced gradual recovery from disabilities. Impact acceleration closed head TBI paradigm causes diffuse TBI (DTBI) without substantial focal brain lesions in rats. DTBI is linked to a significant rate of death, morbidity, and long-term disability. DTBI is difficult to diagnose at the time of hospitalization with imaging techniques making it challenging to take prompt therapeutic action. The weight-drop method without craniotomy is an impact acceleration closed head DTBI model that is used to induce mild/moderate diffuse brain injuries in rodents. Additionally, we have characterized neuropathological and neurobehavioral outcomes of the weight-drop model without craniotomy for inducing closed head DTBI of graded severity with a range of mass of weights (50-450 gm). This chapter also discusses techniques and protocols for measuring numerous functional disabilities and pathological changes in the brain brought on by DTBI.
创伤性脑损伤（TBI）是全球首要的残疾和死亡原因之一。成功治疗 TBI 相关残疾的前提是提高对 TBI 神经生物学的认识、测量治疗带来的恢复动力学的定量变化，以及将在临床前模型中成功追踪恢复的定量方法和技术转化为人类 TBI。在研究和开发中经常使用的 TBI 动物模型包括皮质控制冲击、流体冲击损伤、爆炸伤、穿透性爆炸脑损伤和落体冲击加速度模型。TBI 的临床前模型受益于控制损伤环境和对损伤和治疗引起的残疾逐渐恢复进行生物计量量化的最佳前景。加速度闭合性颅脑损伤范式在大鼠中引起弥漫性 TBI（DTBI）而没有实质性的局灶性脑损伤。DTBI 与高死亡率、高发病率和长期残疾率相关。DTBI 很难通过影像学技术在住院时进行诊断，因此难以采取及时的治疗措施。无开颅手术的落体方法是一种加速度闭合性颅脑 DTBI 模型，用于在啮齿动物中诱导轻度/中度弥漫性脑损伤。此外，我们还对无开颅手术的落体模型进行了特征描述，用于诱导具有不同质量（50-450 克）范围的闭合性颅脑 DTBI 的分级严重程度。本章还讨论了用于测量 DTBI 引起的大脑多种功能障碍和病理变化的技术和方案。
