title: Time course of increased vulnerability of cholinergic neurotransmission following traumatic brain injury in the rat.
abstract: We have previously shown that spatial memory changes following experimental traumatic brain injury (TBI) include long-term changes that are (1) 'overt': detected by routine behavioral assessments, or (2) 'covert': 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 course of recovery of overt and covert spatial memory performance following two magnitudes of experimental TBI. The Morris water maze was used to assess cognitive performance. Rats received either moderate magnitude (6 m/s, 1.77 mm deformation) or low magnitude (6 m/s, 1 mm deformation) impacts through a lateral craniectomy under isoflurane anesthesia. Sham rats underwent identical surgical procedures but were not injured. 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 prior to maze testing. The next day, rats were retested. This testing regimen was repeated, beginning 4, 6, and 10 weeks post-TBI. Results showed that, while the low-magnitude injury produced no overt spatial memory deficits, the moderate-magnitude group exhibited overt deficits during the first test regimen. Also, while both injury magnitudes produced an enhanced sensitivity to spatial memory impairment by scopolamine at two weeks post-TBI, this covert deficit persisted only in the severe group at 4, 6, and 10 weeks post-TBI. Qualitative light microscopy showed that both injury groups had graded cortical necrosis. However, underlying subcortical structures such as the hippocampus appeared intact, with no overt cellular or parenchymal damage to the neuropil. These data suggest three distinct stages of functional recovery: (1) the initial period when overt deficits are present, (2) a period following recovery from overt deficits within which covert deficits can be reinstated by a pharmacological challenge, and (3) a period following recovery from both overt and covert deficits. Covert deficits can persist long after the recovery of overt deficits and, like other neurological deficits, the rate of recovery is dependent on the magnitude of TBI. Finally, spatial memory deficits can occur in the absence of light microscopic evidence of cell death in the hippocampus.
authors.affiliation: Department of Neurosurgery, University of Texas Health Science Center at Houston 77030, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Dixon
authors.forename: S J
authors.initials: SJ
authors.lastname: Liu
authors.forename: L W
authors.initials: LW
authors.lastname: Jenkins
authors.forename: M
authors.initials: M
authors.lastname: Bhattachargee
authors.forename: J S
authors.initials: JS
authors.lastname: Whitson
authors.forename: K
authors.initials: K
authors.lastname: Yang
authors.forename: R L
authors.initials: RL
authors.lastname: Hayes
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001924:Brain Concussion / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D002799:Cholinergic Fibers / Q000473:pathology / Q000502:physiology*; D004924:Escape Reaction / Q000502:physiology; D006624:Hippocampus / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology*; D009410:Nerve Degeneration / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D009949:Orientation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D012601:Scopolamine; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D012601:Scopolamine; D000109:Acetylcholine