Flow thresholds for extracellular purine catabolite elevation in cat focal ischemia.
Ischemic glutamate excitotoxicity may be counteracted by adenosine which appears extracellularly during ischemia as an intermediate purine catabolite and has the potential to modulate glutamate release and its receptor action. The present study was conducted to evaluate the flow threshold for purine catabolite accumulation in relation to that for glutamate elevation in focal ischemia which was induced by middle cerebral artery (MCA) occlusion in halothane anesthetized cats. Assemblies of platinum electrodes and microdialysis probes were inserted into the somatosensory (SF, n = 13) and the auditory (A, n = 9) cortices to assess local cerebral blood flow (CBF) using hydrogen clearance and purine catabolite (adenosine, inosine and hypoxanthine) as well as glutamate concentrations in the dialysate using high-performance liquid chromatography (HPLC). In both investigated areas, purine catabolites were elevated if CBF fell below 25 ml/100 g/min, while glutamate increased at a flow threshold below 20 ml/100 g/min. Maximum elevations of adenosine, inosine and hypoxanthine were 76-, 29- and 11-fold, respectively, that of glutamate was 24-fold. In the range between 20 and 25 ml/100 g/min, significant increases of adenosine (5-15-fold) were measured, while glutamate did not markedly increase. The elevation of adenosine was transient whereas that of inosine, hypoxanthine and glutamate persisted over an ischemic period of 3 h. The higher flow threshold for adenosine may reflect an inherent but time limited protective mechanism against glutamate excitotoxicity.
Max-Planck-Institut für neurologische Forschung, Köln, FRG.
K
K
Matsumoto
R
R
Graf
G
G
Rosner
N
N
Shimada
W D
WD
Heiss
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001303:Auditory Cortex / Q000378:metabolism / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002415:Cats; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004566:Electrodes; D005260:Female; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D011687:Purines / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000378:metabolism / Q000502:physiology
D005971:Glutamates; D011687:Purines; D018698:Glutamic Acid; D000255:Adenosine Triphosphate