Injury severity determines Purkinje cell loss and microglial activation in the cerebellum after cortical contusion injury

Clinical evidence suggests that the cerebellum is damaged after traumatic brain injury (TBI) and experimental studies have validated these observations. We have previously shown cerebellar vulnerability, as demonstrated by Purkinje cell loss and microglial activation, after fluid percussion brain injury. In this study, we examine the effect of graded controlled cortical impact (CCI) injury on the cerebellum in the context of physiologic and anatomical parameters that have been shown by others to be sensitive to injury severity. Adult male rats received mild, moderate, or severe CCI and were euthanized 7 days later. We first validated the severity of the initial injury using physiologic criteria, including apnea and blood pressure, during the immediate postinjury period. Increasing injury severity was associated with an increased incidence of apnea and higher mortality. Severe injury also induced transient hypertension followed by hypotension, while lower grade injuries produced an immediate and sustained hypotension. We next evaluated the pattern of subcortical neuronal loss in response to graded injuries. There was significant neuronal loss in the ipsilateral cortex, hippocampal CA2/CA3, and laterodorsal thalamus that was injury severity-dependent and that paralleled microglial activation. Similarly, there was a distinctive pattern of Purkinje cell loss and microglial activation in the cerebellar vermis that varied with injury severity. Together, these findings emphasize the vulnerability of the cerebellum to TBI. That a selective pattern of Purkinje cell loss occurs regardless of the type of injury suggests a generalized response that is a likely determinant of recovery and a target for therapeutic intervention.