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.

Proteomic identification of nitrated brain proteins in traumatic brain‐injured rats treated postinjury with gamma‐glutamylcysteine ethyl ester: Insights into the role of elevation of glutathione as a potential therapeutic strategy for traumatic brain injury

“…This inactivity prevents effector binding downstream signaling (i.e., glycogen ca- tabolism, etc.). In TBI, glycogen levels are increased compared with control, supporting the downstream effects impaired by GDI (Otori et al, 2004).…”

Increased Pentose Phosphate Pathway Flux after Clinical Traumatic Brain Injury: A [1,2-13C2]glucose Labeling Study in Humans

“…Lastly, PPC flux was determined relative to glycolytic activity, not necessarily accounting for all the excess glucose that was consumed by nonoxidative pathways in the brain, such as glycogen synthesis. Other studies have suggested that these fluxes may be increased after injury as well (Otori et al, 2004). …”

Repeated Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability

“…While it is rational to assume that TBI increases the brain's vulnerability to secondary injury, preconditioning effects have been demonstrated (Otori et al, 2004). Fluid percussion (FP) injury given 1 hr prior to ischemia exaccerbates hippocampal cell loss (Jenkins et al, 1989), but when given 24hr before ischemia it is neuroprotective (Otori et al, 2004).…”