CORTICAL CHOLINERGIC DYSFUNCTION AFTER HUMAN HEAD-INJURY

Loss of cholinergic neurotransmission is implicated in memory impairme nt and cognitive dysfunction after head injury. The aim of the present study was to investigate presynaptic markers, particularly in relatio n to cholinergic neurotransmission in human postmortem brain from pati ents who died following a head injury and age-matched controls. Cholin e acetyltransferase activity and high-affinity nicotinic receptor bind ing sites were assayed in the inferior temporal gyrus, cingulate gyrus , and superior parietal cortex of 16 head-injured patients and 8 contr ols. Synaptophysin immunoreactivity was determined in the left cingula te gyrus from the same patient groups. In the head-injured group, chol ine acetyltransferase activity was consistently reduced in each cortic al region compared to control subjects. The presence of a subdural hae matoma and a prolonged survival period after head injury tended to be associated with lower choline acetyltransferase activity. In contrast to the marked reduction in choline acetyltransferase activity, nicotin e receptor binding was unchanged in head-injured compared to control p atients. Synaptophysin immunoreactivity in the cingulate gyrus was red uced by approximately 30% (p < 0.05) in the head-injured group compare d to controls. Correlation of choline acetyltransferase activity with synaptophysin immunoreactivity indicated there is a deficit of choline rgic presynaptic terminals in postmortem human brain following head in jury.