Recovery of water maze performance in aged versus young rats after brain injury with the impact acceleration model.

Abstract

Clinically, elderly patients have a higher cognitive morbidity from head trauma than young patients. We have modeled injury in aged rats in an effort to elucidate the pathophysiology of this enhanced sensitivity and, in particular, to determine if there are susceptibility differences in forebrain cholinergic innervation in young versus aged rats. Aged (20-23 months) and young (2-3 months) rats were subjected to injury under halothane anesthesia using the Marmarou impact acceleration model. Injury parameters required adjustment downward for the aged rats (323 g at 1.61 m versus 494 g at 2.06 m) to provide equivalent mortality (30% versus 20%) and loss of righting-reflex times (10-12 min average). At 1 week following injury, the aged animals were markedly more impaired in water maze performance than were young rats, and this difference persisted at least up to 5 weeks following injury. The extent of improvement in performance from 1 to 5 weeks was markedly worse for aged animals compared to young animals. Forebrain synaptosomal choline uptake was decreased in aged injured rats by 8-14% at 1, 3, and 5 weeks postinjury, but not decreased in young injured rats. No differences were noted in entorhinal cortex or hippocampal choline uptake. This model effectively demonstrates the markedly increased susceptibility of older animals to head injury and their decreased capacity for recovery. The neurophysiological basis for this difference is presently unknown, but the differences in cognitive dysfunction between young and aged rats appears to be much greater than would seem to be explained by the small differences in forebrain cholinergic innervation.