PURKINJE-CELL VULNERABILITY TO MILD TRAUMATIC BRAIN INJURY

In this study we examined the cerebellar response to mild traumatic br ain injury by assessing microglial activation and Purkinje cell loss, Activated microglia were identified using the antibodies OX-42 and ED- 1 as well as isolectin B4. The anti-Purkinje cell antibody PEP-19 was used to evaluate Purkinje cell loss after injury, The mechanism of cel l injury was examined using a monoclonal antibody to the inducible 72- kDa heat shock protein, A monoclonal antibody to the N-terminal sequen ce of Fos was used as a marker for neuronal activation, There was prog ressive activation of microglia in the cerebellar vermis within a few days after forebrain injury. In coronal sections the processes of acti vated microglia were oriented in ''stripes'' perpendicular to the cort ical surface, In sagittal sections the activated microglia were in irr egularly shaped clusters or in a fan-like distribution that radiated f rom the Purkinje cell layer toward the cortical surface. There was a s ignificant loss of Purkinje cells 7 days postinjury as compared to the control group, There was no evidence of induction of heat shock prote in in the cerebellum, In addition, there was no evidence of induction of c-Fos protein in either the cerebellar cortex or inferior olivary n uclei within the first 3 h after injury, These studies demonstrate tha t a fluid percussive impact to the forebrain results in cerebellar dam age, The close anatomical association between activated microglia and Purkinje cells suggests that Purkinje cell injury is the cause of the microglial activation, The mechanism of Purkinje cell death, however, remains unclear.