Effects of theophylline and cyclohexyladenosine on brain injury following normo- and hyperglycemic ischemia: a histopathologic study in the rat

The present study was designed to determine the effects of theophylline, an adenosine receptor antagonist, and cyclohexyladenosine (CHA), an adenosine receptor agonist, on ischemic brain injury following normo- and hyperglycemic ischemia and reperfusion in fasted male Wistar rats. Moderate hyperglycemia was achieved by administering 17% D-glucose (3 g/kg i.p.), whereas normoglycemic animals received an equal volume of saline. The animals were further divided into two groups: One group was pretreated with either theophylline (0.20 mumol/g i.p.) or an equal volume of saline; the second group received either intraventricular CHA (6.25 nmol) or mock CSF prior to the onset of ischemia. During ischemia, pericranial temperature was maintained at 36 degrees C and EEG was monitored. Cerebral ischemia was induced for 15 min, after which flow was restored and the animals were allowed to recover completely. There were no significant differences in physiologic parameters among the groups studied. Five days following the ischemic episode, the rats were perfused with formalin and the brains subserially sectioned (8 microns) in the coronal plane and stained with celestine blue/acid fuchsin. Histopathologic analysis was performed in a blinded fashion to determine percentage of dead neurons. Hyperglycemic animals had significantly greater ischemic injury in CA1, cortex, and caudate than the normoglycemic group (p < 0.01). Moreover, rats pretreated with theophylline had a significantly (p < 0.01) higher percentage of dead neurons in CA1, cortex, and caudate than corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)