Hypoglycemic Brain Injury in the Rat: Correlation of Density of Brain Damage with the EEG Isoelectric Time: A Quantitative Study

Abstract

Thirty-eight male Wistar rats were exposed to insulin-induced hypoglycemia resulting in periods of cerebral isoelectricity ranging from 10 to 60 min. Plasma glucose levels during cerebral isoelectricity ranged from 0.12 mM to 1.36 mM. Control rats were injected with insulin, but hypoglycemia was terminated with glucose at the stage of large delta-wave EEG slowing. After recovery, the rats were allowed to wake up and survive for 1 wk. The number of dying neurons was assessed with acid-fuchsin/cresyl-violet-stained, whole-brain, subserial sections using direct visual counting of acidophilic, cytoclastic neurons. Brains from control rats that were not allowed to become isoelectric showed no dying neurons. Ten minutes of cerebral isoelectricity produced very minimal brain damage. The density of neuronal necrosis was positively related to the number of minutes of cerebral isoelectricity up to the maximum examined period of 60 min, but showed no correlation with the blood sugar levels. The cerebral cortex, hippocampus, caudate nucleus, spinal cord, and, to a lesser extent, cerebellar Purkinje cells were affected. The distribution of neuronal necrosis was not identical with that seen in ischemia, but, rather, suggested a CSF-borne neurotoxin operant in contributing to the pathogenesis of neuronal necrosis in hypoglycemic brain damage. Neuronal death does not occur in hypoglycemia unless the EEG becomes isoelectric, whatever the blood sugar level. Serious brain damage does not occur until electrocerebral silence has been established for at least several minutes. Neuronal death accelerates after 30 min of EEG isoelectricity in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

“…All animals recovered for 7 days fol lowing ischemia, before transcardial perfusion with phos phate-buffered 4% formaldehyde. The perfusion-fixed brains were dehydrated, paraffin embedded, sectioned at 5 f-Lm, and stained according to the method described by Auer et al (1984). Necrotic neurons stain bright red, while intact cells stain violet.…”

Prevention of Acute/Severe Hypoglycemia-Induced Neuron Death by Lactate Administration

“…Hypoglycemia was induced with regular insulin as described by Auer et al (1984) with minor modifications (Suh et al, 2003). In brief, male Sprague-Dawley rats weighing 250 to 350 g were fasted overnight and hypoglycemia was induced by intraperitoneal injection of 10 U/kg of regular insulin (Novolin-R, Novo Nordisk, Clayton, NC, USA).…”

Adaptive Preservation of ATP and Tolerance to Hypoxia following Carotid Artery Ligation in the Immature Rat

“…After re moval of the brain, the area of cortical pallor in the ipsi lateral cortex was graded on a 4-point scale: 0, pallor not detected; I, <30% of the cortical surface exhibiting pal lor; 2, 30-70% pallor; and 3, >70% pallor. The brains of 23 day olds were sectioned at a thickness of 20 fLm in a cryostat at -15°C, and the sections were stained with thionin and acid fuchsin as described previously (Auer et al, 1984). With these stains, necrotic neurons appear bright red with condensed nuclei.…”