This manuscript was written up check this in accordance with the ARRIVE guidelines. Type 1 diabetes rat For the type 1 diabetes model, rats received repeated intraperitoneal injections of streptozotocin. One month old male Sprague Dawley rats were injected with 50 mg kg STZ. Rats displaying fasting blood glucose levels higher than 200 mg dl 7 days after the first injection were used in this experiment. All rats injected with STZ showed typical symptoms of diabetes such as polydipsia, polyphagia, and polyuria. Although the STZ induced diabetes mellitus model has cer tain caveats, this model offers Inhibitors,Modulators,Libraries a very effective technique that can be used in most rodents. Fasting blood glu cose levels in STZ treated rats were left uncorrected and fell in the range Inhibitors,Modulators,Libraries of 10 to 20 mM.

R M hypoglycemia One week after STZ injection, R M hypoglycemia was induced without anesthesia. After overnight fasting, Inhibitors,Modulators,Libraries rats were given an insulin injection to induce moderate hypoglycemia, as previously described with minor modification. After insulin Inhibitors,Modulators,Libraries injection, blood glucose was measured from the tail vein using ACCU CHEK glucometer at 30 min intervals. Blood glucose levels between 1 and 2 mM were maintained for 1 h. Blood glucose level was increased by intraperitoneal injection of glucose 1 h after moderate hypoglycemia. In the present study we defined moderate hypoglycemia as sustained blood glucose concentrations between 1 to 2 mM without coma. This process was repeated for 5 consecutive days. Rats were randomly assigned to two groups, one for studying the role of oxidative stress and the other group for cogni tive testing 6 weeks post insult.

To test whether NADPH oxidase activation Inhibitors,Modulators,Libraries is involved in R M hypoglycemia induced oxidative injury in hippocampal dendrites, the NADPH R115777 oxidase assembly inhibitor, apocynin, was injected intraperitoneally immediately after R M hypoglycemia. Since half life of apocynin is about 1 h, we believe that apocynin may inhibit glucose reperfusion induced NADPH oxidase activation for 2 to 3 h. Apocynin was dissolved in 1% DMSO and control rats for these studies received equal volumes of vehicle alone. This process was repeated for 5 consecutive days.