The onset of postischemic hypoperfusion in rats is precipitous and may be controlled by local neurons.
OBJECTIVE
Reperfusion following transient global cerebral ischemia is characterized by an initial hyperemic phase, which precedes hypoperfusion. The pathogenesis of these flow derangements remains obscure. Our study investigates the dynamics of postischemic cerebral blood flow changes, with particular attention to the role of local neurons.


METHODS
We assessed local cortical blood flow continuously by laser Doppler flowmetry to permit observation of any rapid flow changes after forebrain ischemia induced by four-vessel occlusion for 20 minutes in rats. To investigate the role of local cortical neurons in the regulation of any blood flow fluctuations, five rats received intracortical microinjections of a neurotoxin (10 micrograms ibotenic acid in 1 microliter; 1.5-mm-depth parietal cortex) 24 hours before ischemia to induce selective and localized neuronal depletion in an area corresponding to the sample volume of the laser Doppler probe (1 mm3). Local cerebral blood flow was measured within the injection site and at an adjacent control site.


RESULTS
Ischemia was followed by marked hyperemia (235 +/- 23% of control, n = 7), followed by secondary hypoperfusion (45 +/- 3% of control, n = 7). The transition from hyperemia to hypoperfusion occurred not gradually but precipitously (maximal slope of flow decay: 66 +/- 6%/min; n = 7). In ibotenic acid-injected rats, hyperemia was preserved at the injection site, but the sudden decline of blood flow was abolished (maximal slope of flow decay: 5 +/- 3%/min compared with 53 +/- 8%/min at the control site; n = 5, p less than 0.001) and no significant hypoperfusion developed (103 +/- 20% of control at 60 minutes).


CONCLUSIONS
These data suggest that the rapid transition to cortical hypoperfusion after forebrain ischemia may be triggered locally by a neuronal mechanism but that this mechanism does not underlie the initial hyperemia.
Frerichs
K U
KU
Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md.
Sirén
A L
AL
Feuerstein
G Z
GZ
Hallenbeck
J M
JM
D000818:Animals; D001794:Blood Pressure; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D007051:Ibotenic Acid / Q000494:pharmacology; D007834:Lasers; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014463:Ultrasonography
D007051:Ibotenic Acid