Traumatic brain injury (TBI) is a major source of death and disability worldwide; however, its pathogenesis is no longer regarded as an immediate, irreversible process that occurs at the time of injury. Long-term alterations in personality, sensory-motor function, and cognition are common among trauma survivors. The pathophysiology of brain injury is very complex, so it is difficult to understand. Establishing models such as weight drop, controlled cortical impact, fluid percussion, Accelerationdeceleration, hydrodynamic and cell line culture, etc., to simulate the event within controlled conditions has been a critical step in better understanding traumatic brain injury and enabling improved therapy. Establishing effective in vivo and in vitro models of traumatic brain injury and mathematical models is described here as part of the discovery of neuroprotective techniques. Some models, such as weight drop, fluid percussion, and cortical impact, help us understand the pathology of brain injury and provide suitable and effective therapeutic doses of the drug. A chemical mechanism such as prolonged or toxic exposure to chemicals and gases causes toxic encephalopathy, an acquired brain injury that may or may not be reversible. This review provides a comprehensive overview of numerous in-vivo and in-vitro models and molecular pathways to advance the knowledge of TBI. It covers traumatic brain damage pathophysiology, including apoptosis, the function of chemicals and genes, and a brief discussion on putative pharmacological remedies.