Influence of hyperglycemia on cerebral adenosine production during ischemia and reperfusion.
We hypothesized that systemic hyperglycemia would alter cerebral adenosine concentrations during ischemia and reperfusion. In the present study, we analyzed brain tissue and cerebrospinal fluid (CSF) from hyperglycemic and normoglycemic rats before ischemia, after 15 min of incomplete forebrain ischemia, and during 60 min of reperfusion. Hyperglycemic rats received 3 g/kg of 17% D-glucose intraperitoneally, which increased blood glucose to 357 +/- 23 mg/100 ml compared with 128 +/- 12 mg/100 ml in normoglycemic rats. Brain tissue was sampled by the freeze-blow technique, and CSF was obtained by collecting cortical perfusate from the closed cranial window. Tissue and CSF were analyzed for adenosine and its metabolites inosine and hypoxanthine, and tissue was also analyzed for adenine nucleotides. Hyperglycemia significantly attenuated the increase in brain tissue and CSF adenosine and its metabolites during ischemia while preserving adenine nucleotide concentrates. This attenuation of ischemic adenosine production persisted after 5 min of reperfusion in tissue and throughout 60 min of reperfusion in CSF. Because adenosine, a cerebral vasodilator, can inhibit the release of neuronal excitotoxins as well as affect neutrophil-endothelial interactions, adenosine has been proposed as an endogenous neuroprotector. Thus the attenuation of adenosine and its metabolites may be a factor in the pathogenesis of increased ischemic brain injury associated with systemic hyperglycemia.
Hsu
S S
SS
Department of Neurological Surgery, University of Washington, Seattle 98104.
Meno
J R
JR
Zhou
J G
JG
Gordon
E L
EL
Winn
H R
HR
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002545:Brain Ischemia / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006943:Hyperglycemia / Q000134:cerebrospinal fluid / Q000378:metabolism*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000134:cerebrospinal fluid / Q000378:metabolism; D007288:Inosine / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D019271:Hypoxanthine; D007288:Inosine; D000241:Adenosine