title: Hypoglycemic brain damage.
abstract: Hypoglycemia was long considered to kill neurons by depriving them of glucose. We now know that hypoglycemia kills neurons actively from without, rather than by starvation from within. Hypoglycemia only causes neuronal death when the EEG becomes flat. This usually occurs after glucose levels have fallen below 1 mM (18 mg/dl) for some period, depending on body glycogen reserves. At the time that abrupt brain energy failure occurs, the excitatory amino acid aspartate is massively released into the limited brain extracellular space and floods the excitatory amino acid receptors located on neuronal dendrites. Calcium fluxes occur and membrane breaks in the cell lead rapidly to neuronal necrosis. Significant neuronal necrosis occurs after 30 min of electrocerebral silence. Other neurochemical changes include energy depletion to roughly 25% of control, phospholipase and other enzyme activation, tissue alkalosis and a tendency for all cellular redox systems to shift towards oxidation. The neurochemistry of hypoglycemia thus differs markedly from ischemia. Hypoglycemia often differs from ischemia in its neuropathologic distribution, a phenomenon applicable in forensic practice. The border-zone distribution of global ischemia is not seen, necrosis of the dentate gyrus of the hippocampus can occur and a predilection for the superficial layers of the cortex is sometimes seen. Cerebellum and brainstem are universally spared in hypoglycemic brain damage. Hypoglycemia constitutes a unique metabolic brain insult.
authors.affiliation: Departments of Pathology and Clinical Neuroscience, Faculty of Medicine, University of Calgary, Calgary, AB, Canada. rauer@ucalgary.ca <rauer@ucalgary.ca>
authors.forename: Roland N
authors.initials: RN
authors.lastname: Auer
mesh_terms: D000471:Alkalosis / Q000378:metabolism; D001923:Brain Chemistry; D001930:Brain Injuries / Q000473:pathology*; D004569:Electroencephalography; D049429:Forensic Pathology; D006801:Humans; D007003:Hypoglycemia / Q000473:pathology*; D008854:Microscopy, Electron; D009336:Necrosis; D009474:Neurons / Q000473:pathology*