EFFECTS OF THEOPHYLLINE AND CYCLOHEXYLADENOSINE ON BRAIN INJURY FOLLOWING NORMOGLYCEMIC AND HYPERGLYCEMIC ISCHEMIA - A HISTOPATHOLOGIC STUDY IN THE RAT
Jg. Zhou et al., EFFECTS OF THEOPHYLLINE AND CYCLOHEXYLADENOSINE ON BRAIN INJURY FOLLOWING NORMOGLYCEMIC AND HYPERGLYCEMIC ISCHEMIA - A HISTOPATHOLOGIC STUDY IN THE RAT, Journal of cerebral blood flow and metabolism, 14(1), 1994, pp. 166-173
The present study was designed to determine the effects of theophyllin
e, 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 o
f saline. The animals were further divided into two groups: One group
was pretreated with either theophylline (0.20 mu mol/g i.p.) or an equ
al volume of saline; the second group received either intraventricular
CHA (6.25 nmol) or mock CSF prior to the onset of ischemia. During is
chemia, 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 m
u m) in the coronal plane and stained with celestine blue/acid fuchsin
. Histopathologic analysis was performed in a blinded fashion to deter
mine percentage of dead neurons. Hyperglycemic animals had significant
ly greater ischemic injury in CA(1) cortex, and caudate than the normo
glycemic group (p < 0.01). Moreover, rats pretreated with theophylline
had a significantly (p < 0.01) higher percentage of dead neurons in C
A(1) cortex, and caudate than corresponding controls. On the other han
d, rats treated with CHA exhibited significantly (p < 0.01) less cereb
ral ischemic injury than corresponding controls, in either normo- or h
yperglycemic conditions. These data confirm previous studies showing t
he deleterious effects of hyperglycemia on cerebral ischemia-reperfusi
on injury. Moreover, our results illustrate a protective effect of ade
nosine on both normo- and hyperglycemic ischemia-reperfusion injury an
d thus support the hypothesis that attenuated cerebral ischemic produc
tion of adenosine contributes to increased tissue injury observed unde
r hyperglycemic conditions.