title: Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat brain.
abstract: Previous studies have demonstrated that traumatic brain injury (TBI) increases the vulnerability of the brain to an acute episode of hypoxia-ischemia. The objective of the present study was to determine whether TBI alters the vulnerability of the brain to a delayed episode of ischemia and, if so, to identify contributing mechanisms. Sprague-Dawley rats were subjected to lateral fluid-percussion (FP) brain injury (n = 14) of moderate severity (2.3-2.5 atm), or sham-injury (n = 12). After recovery for 24 h, all animals underwent an 8-min episode of forebrain ischemia, followed by survival for 6 days. Ischemic damage in the hippocampus and cerebral cortex of the FP-injured hemisphere was compared to that in the contralateral hemisphere and to that in sham-injured animals. Remarkably, the number of surviving CA(1) neurons in the middle and lateral segments of the hippocampus in the FP-injured hemisphere was significantly greater than that in the contralateral hemisphere and sham-injured animals (p < 0.05). Likewise, in the cerebral cortex the number of damaged neurons tended to be lower in the FP-injured hemisphere than in the contralateral hemisphere. These results suggest that TBI decreased the vulnerability of the brain to a delayed episode of ischemia. To determine whether TBI triggers protective metabolic alterations, glycogen levels were measured in cerebral cortex and hippocampus in additional animals 24 h after FP-injury (n = 13) or sham-injury (n = 7). Cortical glycogen levels in the ipsilateral hemisphere increased to 12.9 +/- 6.4 mmol/kg (mean +/- SD), compared to 6.4 +/- 1.8 mmol/kg in the opposite hemisphere and 5.7 +/- 1.3 mmol/kg in sham-injured animals (p < 0.001). Similarly, in the hippocampus glycogen levels in the FP-injured hemisphere increased to 13.4 +/- 4.9 mmol/kg, compared to 8.1 +/- 2.4 mmol/kg in the contralateral hemisphere (p < 0.004) and 6.2 +/- 1.5 mmol/kg in sham-injured animals (p < 0.001). These results demonstrate that TBI triggers a marked accumulation of glycogen that may protect the brain during ischemia by serving as an endogenous source of metabolic energy.
authors.affiliation: Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Otori
authors.forename: Julie C
authors.initials: JC
authors.lastname: Friedland
authors.forename: Grant
authors.initials: G
authors.lastname: Sinson
authors.forename: Tracy K
authors.initials: TK
authors.lastname: McIntosh
authors.forename: Ramesh
authors.initials: R
authors.lastname: Raghupathi
authors.forename: Frank A
authors.initials: FA
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D006003:Glycogen; D005947:Glucose