Pattern of Neuronal and Axonal Damage, Glial Response, and Synaptic Changes in Rat Cerebellum within the First Week following Traumatic Brain Injury

Abstract

AbstractWe examined damage and repair processes in the rat cerebellum within the first week following moderate traumatic brain injury (TBI) induced by lateral fluid percussion injury (LFPI) over the left parietal cortex. Rats were killed 1, 3, or 7 days after the injury or sham procedure. Fluoro-Jade B staining revealed 2 phases of neurodegenerative changes in the cell bodies and fibers: first, more focal, 1 day after the LFPI, and second, widespread, starting on post-injury day 3. Purkinje cell loss was detected in posterior lobule IX 1 day following LFPI. Apoptosis was observed in the cerebellar cortex, on days 1 and 7 following LFPI, and was not caspase- or apoptosis-inducing factor (AIF)-mediated. AIF immunostaining indicated axonal damage in the cerebellar white matter tracts 3- and 7-days post-injury. Significant astrocytosis and microgliosis were noticed on day 7 following LFPI at the sites of neuronal damage and loss. Immunohistochemical labeling with the presynaptic markers synaptophysin and growth-associated protein-43 revealed synaptic perturbations already on day 1 that were more pronounced at later time points following LFPI. These results provide new insights into pathophysiological alterations in the cerebellum and their mechanisms following cerebral TBI.