oxadiazoles and Cerebral-Infarction

In the present study, we have investigated the effects of glycogen synthase kinase-3 (GSK-3) inhibition on infarct volume and neurobehavioral functions in a focal cerebral ischemia model. To achieve our goals, GSK-3 inhibitor II or VIII was injected at several time points and in varing dosages. GSK-3 inhibitor VIII was more effective than inhibitor II, and infarct volume and water content in the VIII group were significantly decreased 24h after the onset of ischemic stroke, as compared with the control group. These protective effects were associated with reductions of TUNEL-positive cells, neutrophil infiltration, glucose levels after ischemia, and GSK-3 enzyme activity. In addition, expressions of death and inflammation-related signals decreased and those of survival-related signals increased. Lastly, neurobehavioral functions were restored to a greater extent in the VIII group than in the control group. Together, these results suggest that GSK-3 inhibition reduces infarct volume and restores neurobehavioral functions.

Topics: Animals; Behavior, Animal; Blood Glucose; Brain Edema; Calcium-Binding Proteins; Caspase 3; Cerebral Infarction; Cyclooxygenase 2; Disease Models, Animal; Glial Fibrillary Acidic Protein; Glycogen Synthase Kinase 3; Microfilament Proteins; Oxadiazoles; Poly(ADP-ribose) Polymerases; Protein Kinase Inhibitors; Pyridines; Rats; Rats, Sprague-Dawley; Thiazoles; Urea

The potent and selective AMPA receptor antagonist NBQX was tested for cytoprotective properties in an adult rat model of transient focal neocortical ischemia. Nineteen spontaneously hypertensive rats sustained 2 h of middle cerebral artery occlusion, followed by 22 h of recirculation. Ninety minutes following the onset of ischemia, at the time of, and 30 min following reperfusion, they received i.p. injections of either saline (n = 10) or 30 mg kg-1 of NBQX (n = 9). Saline-treated rats had a mean volume of neocortical infarction ( +/- s.d.) of 181 +/- 31 mm3, while NBQX-treated rats sustained significantly less damage, 125 +/- 19 mm3 (p less than 0.001). Regional cerebral blood flows during ischemia and reperfusion were not affected by the drug. We suggest that the AMPA receptor may play an important role in ischemic cerebral infarction.

Topics: Animals; Blood Pressure; Carbon Dioxide; Cerebral Infarction; Cerebrovascular Circulation; Ischemic Attack, Transient; Male; Oxadiazoles; Oxygen; Partial Pressure; Quinoxalines; Rats; Rats, Inbred SHR; Receptors, AMPA; Receptors, Neurotransmitter