Whether R selleck MEK162 M hypoglycemia causes cognitive impair ment remains an important question. Repetitive hypoglycemia in the developing brain causes selective impairment of synaptic plasticity, in the absence of be induced after only a single episode of moderate hypoglycemia. Neither diabetic nor non diabetic rats showed oxidative injury after only one episode, suggest ing that repetitive moderate hypoglycemia events are required to induce oxidative injury in the hippocampal dendritic area. Inhibitors,Modulators,Libraries Our results also confirm previous find ings that hypoglycemia induces lipid peroxidation in discrete regions of the forebrain. Previously, McNay and Sherwin published the intriguing result that R M hypoglycemia actually led to cognitive im provement in rats. In the Inhibitors,Modulators,Libraries study, they performed a spatial working memory test shortly after R M hypoglycemia.

This improvement was Inhibitors,Modulators,Libraries equal in diabetic and non diabetic rats, in contrast to the present study. However, a major difference between these studies is that behavioral testing in the present study was conducted 6 weeks after R M hypoglycemia. Another study showed that R M hypoglycemia prevented subse quent severe hypoglycemia induced neuronal death and cognitive impairment. This acute preconditioning ef fect is not relevant to the chronic functional impairment described here. Microglial activation is also induced by severe hypoglycemia, and can contribute to neuronal injury, by releasing several neurotoxic substances, includ hippocampal neuronal death, suggesting that impaired synaptic plasticity in the hippocampus caused by repeti tive hypoglycemia could underlie memory and cognitive deficits observed in diabetic children.

Inhibitors,Modulators,Libraries In the present study, we tested the hypothesis that R M hypoglycemia may cause oxidative injury in hippocampal dendrites. To do this, we subjected young diabetic and healthy rats to R M hypoglycemia and evaluated by immunostaining for 4HNE, an,B unsaturated hydro xyalkenal produced by lipid peroxidation in cells. 4HNE immunoreactivity in the hippocampal dendritic area was substantially increased after sequential hypoglycemic events, and was higher in diabetic rats compared to non diabetic rats. Next we asked if oxidative injury could ing superoxide, nitric oxide, and metalloproteinase In the present study, we found that R M hypoglycemia also induced microglial activation in the hippocampus, as seen in severe hypoglycemia, and diabetic rats showed higher microglial activation after R M hypoglycemia.

Thus, this confirms that the inflam matory response was also induced after R M hypoglycemia, but whether this inflammatory response contributes to the oxidative stress or later cognitive im pairment is not established. Debate continues over the role of hypoglycemia and or hyperglycemia Inhibitors,Modulators,Libraries sellckchem in producing cognitive impairment in type 1 diabetes.