Influence of hyperglycemia on cerebral adenosine production during ischemia and reperfusion

Abstract

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.

Adenosine and Neopterin Levels in Cerebrospinal Fluid of Patients with Neurological Disorders.

“…This is due to the short half-life of adenosine (5,30), because adenosine is taken up soon in synaptic terminals and glial cells. The adenosine levels of the patients with acute cerebral infarction in the present study are consistent with a previous report of rat hypoxia (34). The neopterin levels in the CSFof the present patients with HAM/TSPas well as those with acute meningitis were significantly increased (35)(36)(37)(38).…”

Ischemia Induces Significant Changes in Purine Nucleoside Concentration in the Retina-Choroid in Rats

“…In the cerebral cortex, for example, adenosine increased blood flow and decreased the release of excitatory amino acids Sciotti et al, 1992). Increases in adenosine concentration in the cerebral cortex were detected within one minute after the onset of ischemia or hypoxia, and increased concentrations were noted with reperfusion (Hsu et al, 1991 ;Winn, Rubio and Berne, 1981).…”

Biology of metabolic syndrome in a vascular patient

“…46,47 Elevated glucose concentrations during an acute ischemic stroke predisposes patients to parenchymal hematoma, which in turn determines a non-favorable outcome at three months. The increases in glucose concentrations have been shown to lower the neuronal ischemic threshold [48][49][50] and potentiate infarct volume after focal ischemia. 51,52 We have shown that the presence of the prediabetic state, metabolic syndrome, is prevalent among patients undergoing carotid revascularization and that these patients are at a greater risk for perioperative morbidity as well as stroke, MI and major adverse events (MAEs) during follow-up when compared with patients without metabolic syndrome.…”