Extracellular correlates of glutamate toxicity in short-term cerebral ischemia and reperfusion: a direct in vivo comparison between white and gray matter.
Glutamate toxicity and cellular calcium overload are thought to be pathophysiological key factors not only in gray matter (GM) but also in white matter (WM) ischemia. Correlates of excitotoxicity have never been directly investigated in vivo in GM and WM ischemia and reperfusion. We measured simultaneously amino acids, purines, and calcium in relation to tissue depolarization using microdialysis and ion-selective electrodes and regional CBF using hydrogen clearance in GM and WM of cats during 10 min of global ischemia and 120 min of reperfusion. CBF ceased during ischemia. Reperfusion was followed by hyperperfusion that turned into hypoperfusion within 60 min in both GM and WM. Direct current potential decreased in ischemia to around -15 mV in GM and -10 mV in WM and shifted back after reperfusion towards control levels in both compartments. Extracellular calcium decreased in GM during ischemia, whereas it increased in WM. After reperfusion, calcium returned to control levels in both GM and WM. Glutamate, aspartate, GABA, and taurine increased in GM but not in WM during ischemia and reperfusion. Adenosine increased transiently in both compartments peaking during the first minutes of reperfusion, and returned thereafter to control levels. Contrasting with GM, deleterious processes such as glutamate accumulation and cellular Ca(2+) influx do not occur in WM during short-term ischemia and reperfusion. Rather, an intrinsic neuroprotective role of adenosine may be discussed. In our view, therefore, therapeutic strategies against glutamate toxicity in short-term ischemia and reperfusion should be mainly focused on GM.
Dohmen
Christian
C
Max-Planck-Institut für neurologische Forschung, Gleueler Street 50, 50931 Köln, Germany. chris@pet.mpin-koeln.mpg.de
Kumura
Eiji
E
Rosner
Gerd
G
Heiss
Wolf-Dieter
WD
Graf
Rudolf
R
D000241:Adenosine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002415:Cats; D002560:Cerebrovascular Circulation / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D008297:Male; D017551:Microdialysis; D011687:Purines / Q000378:metabolism; D015427:Reperfusion Injury / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D011687:Purines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D002118:Calcium