Weight Drop Models of Traumatic Brain Injury in Rats Associated with Cognitive Disorders and Glial Scar Formation: A Systematic Review

Objective: Traumatic brain injury (TBI) causes persistent cognitive disorders due to glial scar formation, inhibiting axonal regeneration. Targeting glial scar formation may improve TBI-related cognitive disorders, and require standardized animal models for research. This review aims to identify a weight drop model inducing cognitive disorders and glial scar formation in rats with TBI, supporting further investigations. Methods: A literature search using PubMed, Science Direct, and ProQuest databases identified relevant articles. Inclusion criteria were randomized controlled trials published in English, in full text, between 2012 and 2022. Review articles and abstracts were excluded. Key words were chosen via the P.I.C.O framework, and article quality was assessed using the Systematic Review Center for Laboratory Animal Experimentation guideline by three reviewers. Results: Among 1,042 articles, 32 studies demonstrated cognitive disorders in rats using the weight drop model. Three studies explored glial scar formation and found that two weight drop methods were associated with cognitive disorders and glial scar formation in rats with TBI: applying a 10-gram load from a 5 cm height to the exposed heads of Sprague–Dawley rats or using a 200 gram weight from a 2.5 cm height to the exposed skulls of mice. Conclusion: Two weight drop model methods were found to induce the formation of glial scar, which consequently resulted in persistent cognitive disorders. These discoveries provide significant insights for future research on potential interventions aimed at preventing glial scar formation and improving cognitive disturbances in TBI. Clinically, this research holds significant promise for informing treatment strategies in TBI patients by identifying targets to prevent or reverse glial scar formation. Such interventions could reduce cognitive decline, improve rehabilitation outcomes, and support the restoration of brain function. Early therapeutic approaches targeting glial scars may enable timely and effective strategies to minimize permanent neurological damage and enhance recovery in TBI patients.