Traumatic brain injury elevates glycogen and induces tolerance to ischemia in rat brain.
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.
Otori
Tatsuo
T
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Friedland
Julie C
JC
Sinson
Grant
G
McIntosh
Tracy K
TK
Raghupathi
Ramesh
R
Welsh
Frank A
FA
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
D006003:Glycogen; D005947:Glucose