An Experimental Model of Closed Head Injury in Mice: Pathophysiology, Histopathology, and Cognitive Deficits

The present study describes the characterization of an experimental model of closed head injury (CHI) in the mouse. This model is a modification of a setup described and used previously in the rat. The weight-drop device was modified and adapted to the size and weight of the mouse and the typical parameters that define the severity of the injury and its outcome were evaluated. The posttraumatic accumulation of water, i.e., cerebral edema, the disruption of the blood–brain barrier (BBB), histopathology, motor and cognitive functions were studied up to 30 days following CHI. Increases in cerebral water content and of BBB permeability were observed in the injured hemisphere at 4 h (p < 0.05) and 24 h (p < 0.01) postinjury, respectively. By 7 days, edema disappeared, while the BBB remained open for up to 30 days. The motor function was evaluated by a set of criteria termed neurological severity score (NSS). NSS was severely impaired immediately after CHI and later showed a spontaneous progressive recovery, although some residual deficits, mainly of beam-walk and balance, were still present at 30 days. Mice trained in the Morris water maze before the injury demonstrated highly significant deficits in memory retention up to at least 11 days postinjury (p < 0.01). Histopathological analysis revealed significant neuronal cell death in CA1, CA2, and CA3 regions of the left hippocampus following CHI. However, in the right hippocampus, overt neuronal cell death was observed only in area CA3 at 7 days after CHI. These results suggest that the modified model of CHI in mice can reproduce the posttraumatic sequelae observed in rats and show that some of the data obtained in this model are essentially similar to those observed in human head injury. The experimental model of CHI in mice may be a useful tool for studies in animals that carry specific genetic alterations, aimed at manipulating neurochemical pathways involved in the pathophysiology of brain damage.