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- Title
Cortical Fluoro-Jade staining and blunted adrenomedullary response to hypoglycemia after noncoma hypoglycemia in rats.
- Authors
Tkacs, Nancy C.; Yanhua Pan; Raghupathi, Ramesh; Dunn-Meynell, Ambrose A.; Levin, Barry E.
- Abstract
Intensive insulin therapy in patients with type 1 diabetes mellitus reduces long-term complications; however, intensive therapy is also associated with a three-fold increase in hypoglycemic episodes. The present study in conscious rats characterizes the physiologic and neuropathologic consequences of a single episode of moderate hypoglycemia. In this model, intravenous insulin is used to reduce plasma glucose to 30 to 35 mg/dL for 75 mins. This single hypoglycemic insult acutely induces hypoglycemia-associated autonomic failure (HAAF), with epinephrine responses to hypoglycemia reduced more than 36% from control. Neuropathology after this insult includes the appearance of dying cells, assessed with the marker Fluoro-jade B (FJ). After hypoglycemic insult, FJ+ cells were consistently seen in subdivisions of the medial prefrontal cortex, the orbital cortex, and the piriform cortex. There was a significant correlation between depth of hypoglycemia and number of FJ+ cells, suggesting that there is a critical threshold below which vulnerable cells begin to die. These data suggest that there is a population of cells that are vulnerable to moderate levels of hypoglycemia commonly experienced by patients with insulin-treated diabetes. These cells, which may be neurons, are primarily found in cortical regions implicated in visceral perception and autonomic control, raising the possibility that their loss contributes to clinically reported deficits in autonomic and perceptual responses to hypoglycemia.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1645–1655. doi:10.1038/sj.jcbfm.9600152; published online 18 May 2005
- Subjects
INSULIN; DIABETES; THERAPEUTICS; PHYSIOLOGY; NEUROLOGICAL disorders; HYPOGLYCEMIA; GLUCOSE
- Publication
Journal of Cerebral Blood Flow & Metabolism, 2005, Vol 25, Issue 12, p1645
- ISSN
0271-678X
- Publication type
Article
- DOI
10.1038/sj.jcbfm.9600152