• C E Dixon, R J Hamm, W C Taft, and R L Hayes.
• Department of Neurosurgery, University of Texas Health Science Center at Houston.
• J. Neurotrauma. 1994 Jun 1;11(3):275-87.

AbstractEvidence suggests that prolonged memory deficits in several neurodegenerative diseases are attributable to deficits in central cholinergic neurotransmission. In traumatic brain injury (TBI), such cholinergic deficits also may contribute to prolonged memory disturbances. This study determined whether moderate magnitudes of TBI produced by controlled cortical impact and mild magnitudes of experimental TBI produced by a new closed head impact technique in rats would produce an enhanced vulnerability to the memory disruptive effects of scopolamine, a muscarinic cholinergic receptor antagonist. Water maze performance was used to determine changes in cholinergic hippocampal function following TBI. In the first experiment, rats received a moderate level of TBI by means of a controlled cortical impact. A Morris water maze task assessed spatial memory function on days 30-34 postinjury. During the 5 day assessment period, statistical analyses showed a group main effect for swim latency. Subsequent post hoc analyses indicated that injured rats had significantly longer latencies on days 30 and 31 (p < 0.05, injury vs sham controls). By days 32-35, injured rats showed no statistically significant deficits in spatial memory performance. On day 35, scopolamine (1 mg/kg, IP) was injected into injured rats and sham-injured rats 15 min prior to being retested in the maze. Results showed that although the scopolamine had no effects on the performance of the sham-injured rats, the same dose significantly (p < 0.05) increased the latency to find the hidden platform in the injured group. In the second experiment, rats received a mild concussive closed head impact. Water maze performance was assessed on days 8-12 postinjury. No significant water maze performance deficits were observed. On day 13, injured and uninjured rats were pharmacologically challenged with scopolamine (1 mg/kg) and retested. Similar to the first experiment, injured rats manifested a significantly greater (p < 0.05) sensitivity to scopolamine than sham controls. The results from both experiments suggest that concussive and more severe levels of TBI can produce an enhanced vulnerability to disruption of cholinergically mediated memory function, even when memory function appears normal in the absence of secondary challenges. These data demonstrate that covert deficits can persist after the recovery of normal function. These deficits may be attributable to a decrease in the ability of cholinergic neurons to function properly. These data also provide important insights into features of receptor-coupled disturbances that could contribute to the maintenance of enduring cognitive deficits following TBI.

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