TIME-COURSE OF INCREASED VULNERABILITY OF CHOLINERGIC NEUROTRANSMISSION FOLLOWING TRAUMATIC BRAIN INJURY IN THE RAT

We have previously shown that spatial memory changes following experim ental traumatic brain injury (TBI) include long-term changes that are (1) 'overt': detected by routine behavioral assessments, or (2) 'cover t': undetected in the absence of a secondary pharmacological challenge , such as by the cholinergic antagonist, scopolamine. Our objective in this study was to extend this finding by characterizing the time cour se of recovery of overt acid covert spatial memory performance followi ng two magnitudes of experimental TBI. The Morris water maze was used to assess cognitive performance. Rats received either moderate magnitu de (6 m/s, 1.7 mm deformation) or low magnitude (6 m/s, 1 mm deformati on) impacts through a lateral craniectomy under isoflurane anesthesia. Sham rats underwent identical surgical procedures but were not injure d. To avoid motor deficits, water maze testing started two weeks post- injury. Rats were given four trials per day for seven consecutive days . For each trial, latency to find a hidden platform was timed. On the sixth, rats were injected (i.p.) with scopolamine (1 mg/kg) 15 min pri or to maze testing. The next day, rats were retested. This testing reg imen was repeated, beginning 4, 6, and 10 weeks post-TBI. Results show ed that, while the low-magnitude injury produced no overt spatial memo ry deficits, the moderate-magnitude group exhibited overt deficits dur ing the first test regimen. Also, while both injury magnitudes produce d an enhanced sensitivity to spatial memory impairment by scopolamine at two weeks post-TBI, this covert deficit persisted only in the sever e group at 4, 6, and 10 weeks post-TBI. Qualitative Light microscopy s howed that both injury groups had graded cortical necrosis. However, u nderlying subcortical structures such as the hippocampus appeared inta ct, with no overt cellular or parenchymal damage to the neuropil. Thes e data suggest three distinct stages of functional recovery: (1) the i nitial period when overt deficits are present, (2) a period following recovery from overt deficits within which covert deficits can be reins tated by a pharmacological challenge, and (3) a period following recov ery from both overt and covert deficits. Covert deficits can persist l ong after the recovery of overt deficits and, like other neurological deficits, the rate of recovery is dependent on the magnitude of TBI. F inally, spatial memory deficits can occur in the absence of light micr oscopic evidence of cell death in the hippocampus.