**4. Rodent models of TBI**

Multiple rodent models have been used to study the role of inflammation in TBI. Due to the variety of injury causes and individual patient health effects, human TBI exhibits multifaceted disease processes, and different animal models are used to recapitulate different aspects of human injury. Here, we discuss three common mouse models of TBI: weight drop, fluid percussion injury (FPI), and controlled cortical impact (CCI). All three of these models generate TBI by direct impact, either applied directly to the brain through a craniectomy or applied to the intact skull. While each of these models replicate certain features of human TBI, no one model fully expresses the varied picture of clinical TBI.

• Weight drop and fluid percussion injury are both used to produce diffuse injury in rodent models of TBI. Weight drop injury relies on gravity-driven fall of the weight to generate injury. Injury severity can be controlled by adjusting both the height of the drop and the mass of the weight used. Modification of injury severity allows this model to reproduce features of mild, moderate, or severe TBI. Weight drop injury results in cortical cell death, cerebral edema, neuroinflammation, and blood-brain barrier compromise, and this method of

injury is relatively time-efficient to perform [18, 19]. In addition, weight drop injury results in demonstrable cognitive deficits, which may reproduce features of human TBI [20].

