Hypoglycemic brain damage is a different global brain insult from cardiac arrest encephalopathy. We here follow the path of glucose from blood to the brain interstitial space, into the cell, through glycolysis into the Krebs cycle, including the consequent new homeostasis in amino acid metabolism that gives rise to increased aspartic acid within cells. Leakage of aspartate massively floods the extracellular space to kill neurons, while continued turning of a truncated form of the Krebs cycle keeps most brain cells alive. Endogenous substrates are utilized, chiefly phospholipids and fatty acids. The duration of tolerable insult is much longer for hypoglycemia than ischemia, which also releases more glutamate than aspartate into the brain interstitium. The neuropathology in humans is not always distinguishable, but if there is dentate gyrus destruction, a very late event in global ischemia, the distinction of hypoglycemic from ischemic damage can be made. Hypoglycemic brain damage occurs in hospitals, attempted suicide and homicide.
KeywordsHypoglycemia Clinical Experimental Glucose EEG Cortex Hippocampus Electron Microscopy
- Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS (2002) Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab 22:271–279CrossRefPubMedGoogle Scholar
- Patti ME, McMahon G, Mun EC, Bitton A, Holst JJ, Goldsmith J, Hanto DW, Callery M, Arky R, Nose V, Bonner-Weir S, Goldfine AB (2005) Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia 48:2236–2240CrossRefPubMedGoogle Scholar
- Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA (2007) Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([R-R*,S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther 321:45–50CrossRefPubMedGoogle Scholar