Hypoglycemic brain injury: Potentiation from respiratory depression and injury aggravation from hyperglycemic treatment overshoots

Hypoglycemia can cause brain dysfunction, brain injury, and death. The pres ent study seeks to broaden current information regarding mechanisms of hypo glycemic brain injury by investigating a novel etiology. The cat's high res istance to brain injury from hypoglycemia suggested that additional influen ces such as respiratory depression might play a facilitating role. Three gr oups of cats were exposed to fasting and insulin-induced hypoglycemia (HG; n = 6), euglycemic respiratory depression (RD; n = 5), and combined hypogly cemic respiratory depression (HG/RD; n = 10). The HG animals were maintaine d at <1.5 mmol (mean I mmol) serum glucose concentration for 2 to 6.6 hours . The respiratory depression was associated with Pao, and Pace, values of s imilar to 50 mm Hg for hour and of similar to 35 and similar to 75 mm Hg, r espectively, for the second hour. Magnetic resonance diffusion-weighted ima ging estimated brain energy state before, during, and after hypoglycemia. T he hypoglycemic respiratory depression exposures were terminated either to euglycemia(n = 4) or to hyperglycemia (n = 6). Brain injury was assessed af ter 5 to 7 days of survival. Cats exposed to hypoglycemia alone maintained unchanged diffusion coefficients; that is, they lacked evidence of brain en ergy failure and all six remained brain-intact. Only 1 of 5 euglycemic RD b ut 10 of 10 HG/RD cars developed brain damage (HG and RD vs. HG/RD, P < 0.0 1). This difference in brain injury rates suggests injury potentiation by h ypoglycemia and respiratory depression acting together. Three injury patter ns emerged, including activation of microglia, selective neuronal necrosis, and laminar cortical necrosis, Widespread activation of microglia suggesti ng damage to neuronal cell processes affected all damaged brains. Selective neuronal necrosis affecting the cerebral cortex, hippocampus, and basal ga nglia was observed in all but one case, instances of laminar cortical necro sis were limited to cats exposed to hypoglycemic respiratory depression tre ated with hyperglycemia. Thus, treatment with hyperglycemia compared with e uglycemia after hypoglycemic respiratory depression exposures significantly increased the brain injury scores (24 +/- 6 vs. 13 +/- 2 points: P < 0.05) . This new experimental hypoglycemia model's contribution lies in recognizi ng additional factors that critically define the occurrence of hypoglycemic brain injury.