title: Recurrent hypoglycemia increases oxygen glucose deprivation-induced damage in hippocampal organotypic slices.
abstract: More than 65% of mortality among diabetics is due to stroke and heart disease. The major side effect of intensive therapy in both type 1 and type 2 diabetics is recurrent hypoglycemic episodes (RH). Our previous study in a rat model of insulin-requiring diabetes indicated that RH exacerbates cerebral ischemic damage. Studies related to RH in hypoglycemia unawareness suggest that RH may be deleterious to outcome following cerebral ischemia owing to systemic effects, since hormonal response to hypoglycemia is impaired following RH. The goal of the present study was to determine if RH increases oxygen-glucose deprivation (OGD)-induced damage in hippocampal organotypic slices, which are devoid of systemic influence. Hippocampal slices cultured in ex vivo conditions for 9-10 days were exposed to ten 30-min episodes of "hypoglucose" (to mimic the hypoglycemic condition) medium (1.06 mM) twice a day. Slices were exposed to OGD 12h after the last hypo/normo-glucose exposure. OGD in control slices resulted in 60% neuronal death. The percentage of cell death in RH-treated slices was significantly higher by 24% than in control slices. The results demonstrate that RH can affect brain cells in the absence of humoral influence. In conclusion, the previous exposure of hippocampal slices to RH exacerbates OGD-induced damage. Understanding the mechanism by which RH increases ischemic damage in diabetics will help improve outcome following stroke.
authors.affiliation: Cerebral Vascular Disease Research Center, Department of Neurology, 1420 NW 9th Ave., TSL/203E, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
authors.forename: Kunjan R
authors.initials: KR
authors.lastname: Dave
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: Ami P
authors.initials: AP
authors.lastname: Raval
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D007003:Hypoglycemia / Q000150:complications* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology*; D007328:Insulin / Q000494:pharmacology; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000473:pathology; D009924:Organ Culture Techniques; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D016202:N-Methylaspartate; D005947:Glucose; D010100:Oxygen