Recurrent Moderate Hypoglycemia Ameliorates Brain Damage and Cognitive Dysfunction Induced by Severe Hypoglycemia

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FIG. 3.
FIG. 3.

Recurrent hypoglycemia limits brain cell death 1 week following 90 min of severe hypoglycemia. A: Representative H-E staining of the cortex and hippocampal structures, CA1, and the dentate gyrus (DG), 1 week following 90-min severe hypoglycemic or euglycemic clamps in RH-SH90, RH-EUG, CON-SH90, and CON-EUG rats. Rats that underwent severe hypoglycemia had damaged neurons characterized by pyknotic nuclei (green arrows). Scale bar = 100 μm. B: Fluoro-Jade B–positive cells (green fluorescence) in the cortex, hippocampal CA1 region, and dentate gyrus of the same four treatment groups. Scale bar = 100 μm. C: Blood glucose was not significantly different between CON-SH90 (open circles) (n = 9) and RH-SH90 (closed circles) (n = 8) rats during 90 min of severe hypoglycemia. Blood glucose was clamped at equal levels of euglycemia in CON-EUG (open triangles) (n = 9) and RH-EUG (closed triangles) (n = 11) rats for 90 min. D: Following 90 min of severe hypoglycemia, the markedly increased number of FJB+ cells in the cortex, CA1, and dentate gyrus observed in the CON-SH90 rats (diagonal hatch) was significantly (*P < 0.05) reduced in RH-SH90 rats (gray horizontal hatch). Bars representing Fluoro-Jade B–positive cells in CON-EUG and RH-EUG groups are not visible in this figure because no appreciable brain damage was observed in euglycemic rats not exposed to severe hypoglycemia. E: CON-EUG and RH-EUG rats experienced no seizure-like behavior. Rats exposed to 90 min severe hypoglycemia exhibited seizure-like behavior, although RH-SH90 rats had significantly less seizure-like behavior than CON-SH90 rats (*P < 0.01). F: In rats that experienced severe hypoglycemia (RH-SH90 and CON-SH90), seizure-like behaviors positively correlated with the amount of Fluoro-Jade B cells in the hippocampus (R = 0.572; P < 0.05). (A high-quality digital representation of this figure is available in the online issue.)

This Article

  1. Diabetes vol. 59 no. 4 1055-1062