Purkinje cell vulnerability to mild and severe forebrain head trauma.

Pathophysiological changes in the cortex, thalamus, and hippocampus have been implicated as contributors to motor and cognitive deficits in a number of animal models of traumatic brain injury (TBI). Indirect cerebellar injury may contribute to TBI pathophysiology because impairment of motor function and coordination are common consequences of TBI, but are also domains associated with cerebellar function. However, there is a lack of direct evidence to support this claim. Hence, in this study, a dose-response relationship of the cerebellum's susceptibility was determined at four grades of fluid percussion injury (1.5, 2.0, 2.5, and 3.0 atm) applied in the right lateral cerebral cortex of adult male Sprague-Dawley rats. Evidence suggests primary and secondary injury mechanisms resulting in selective cerebellar Purkinje neuron (PN) loss, whereas interneurons of the molecular layer were spared. The posterior region of the cerebellar vermis displayed significant PN loss (p = 0.001) at 1 day postinjury, whereas the gyrus of the horizontal fissure and gyrus of lobules III and IV exhibited delayed PN loss at higher levels of injury severity. Interestingly, neither terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) or cleaved caspase-3 colocalized with PNs at any time point or injury severity. Expression of calbindin-28k increased in regions of greatest PN loss, suggesting that the surviving PNs possess higher calcium-buffering capacities, which may account for their survival.