A mouse model of temporal lobe contusion

Trauma to the brain can induce a contusion characterized by a discrete intracerebral or diffuse interstitial hemorrhage. In humans, "computed tomography (CT)-positive", i.e., hemorrhagic, temporal lobe contusions (tlCont) have unique sequelae. tlCont confers significantly increased odds for moderate or worse disability and the inability to return to baseline work capacity compared to intra-axial injuries in other locations. Patients with tlCont are at elevated risks of memory dysfunction, anxiety and post-traumatic epilepsy due to involvement of neuroanatomical structures unique to the temporal lobe including the amygdala, hippocampus and ento-/perirhinal cortex. Because of the relative inaccessibility of the temporal lobe in rodents, no preclinical model of tlCont has been described, impeding progress in elucidating the specific pathophysiology unique to tlCont. Here, we present a minimally invasive mouse model of tlCont with the contusion characterized by a traumatic interstitial hemorrhage. Mortality was low and sensorimotor deficits (beam walk, accelerating rotarod) resolved completely within 3-5 days. However, significant deficits in memory (novel object recognition, Morris water maze) and anxiety (elevated plus maze) persisted at 14-35 days, and non-convulsive electroencephalographic seizures and spiking were significantly increased in the hippocampus at 7-21 days. Immunohistochemistry showed widespread astrogliosis and microgliosis, bilateral hippocampal sclerosis, bilateral loss of hippocampal and cortical inhibitory parvalbumin neurons, and evidence of interhemispheric connectional diaschisis involving the fiber bundle in the ventral corpus callosum that connects temporal lobe structures. This model may be useful to advance our understanding of the unique features of tlCont in humans.