Moderate Traumatic Brain Injury Triggers Rapid Necrotic Death of Immature Neurons in the Hippocampus

Abstract

Traumatic brain injury (TBI) causes cell death predominantly in the cerebral cortex, but there is additional secondary cell death in the hippocampus. We previously found that most of the dying cells in the mouse hippocampus are newborn immature granular neurons in a mouse model of lateral controlled cortical impact (CCI) injury with a moderate level of impact. It is not known how long this selective cell death in the hippocampal dentate gyrus lasts, and how it is induced. Using Fluoro-Jade B and immunohistochemistry, we show that most of the neuron death in the hippocampus occurs within 24 hours after TBI and that cell death continues at low level for at least another 2 weeks in this lateral CCI model. Most of the dying immature granular neurons did not exhibit morphologic characteristics of apoptosis, and only a small subpopulation of the dying cells was positive for apoptotic markers. In contrast, most of the dying cells coexpressed the receptor-interacting protein 1, a marker of necrosis, suggesting that immature neurons mainly died of necrosis. These results indicate that moderate TBI mainly triggers rapid necrotic death of immature neurons in the hippocampus in a mouse CCI model.