Children with type 1 diabetes who suffer recurrent and severe hypoglycemia while younger than 5 years old have impaired mental abilities later in life. The combin ation of an early onset of diabetes and recurrent epi sodes of hypoglycemia appears to be associated with reduced attention and spatial memory in adolescence. Within the diabetic group, verbal intelligence was reduced product info with increased exposure to hyperglycemia, but not to hypoglycemia. In contrast, spatial Inhibitors,Modulators,Libraries intelligence and delayed recall were reduced only with repeated hypoglycemia, particularly when hypoglycemic episodes occurred before the age of 5 years. Recurrent episodes of mild moderate hypoglycemia are associated with a decreased perception of the hypoglycemic state and blunted secretion of counter regulatory hormones, phenomena termed hypoglycemia unawareness and hypoglycemia associated autonomic failure, respectively.

In diabetic patients, even mild to moderate hypoglycemia may produce a sig nificant increase in low frequency EEG activity and impair cognitive function. Several studies have sought to determine the cognitive impact of recurrent hypoglycemia, but results from clinical studies have been mixed and the question of whether recurrent exposure to severe hypoglycemia promotes Inhibitors,Modulators,Libraries long term cognitive dys function is unresolved. There have been several studies performed to deter mine whether neuronal death is induced after moderate hypoglycemia, which is defined as low blood glucose levels without the presence of isoelectric EEG.

These studies concluded that moderate hypoglycemia induced scattered neuronal death in the cerebral cortex layer 2 3, but not in the hippocampus. Yamada et al. also found that moderate hypoglycemia led to no hippo campal neuronal death, however, they did observe sig nificantly deteriorated synaptic plasticity, demonstrated by an inability to induce long term Inhibitors,Modulators,Libraries Inhibitors,Modulators,Libraries potentiation at CA1 synapses. Thus, Inhibitors,Modulators,Libraries we speculated that repetitive episodes of moderate hypoglycemia might lead to synap tic injury in the hippocampus in the absence of apparent neuronal somatic injuries in the hippocampus, and con sequently, the development of cognitive impairments. To date, several hypoglycemia experiments have been performed with normal adult rodents, therefore the clinical implication of these studies is not readily apparent since moderate hypoglycemia com monly occurs in juvenile type 1 diabetes patients. There fore, the present study was conducted in 1 month old young rats that were rendered diabetic by streptozotocin injection, next mimicking juvenile type 1 diabetes. To test our hypothesis, the present study has addressed five questions.