title: Metabolic and perfusion responses to recurrent peri-infarct depolarization during focal ischemia in the Spontaneously Hypertensive Rat: dominant contribution of sporadic CBF decrements to infarct expansion.
abstract: Peri-infarct depolarizations (PIDs) contribute to the evolution of focal ischemic lesions. Proposed mechanisms include both increased metabolic demand under conditions of attenuated perfusion and overt vasoconstrictive responses to depolarization. The present studies investigated the relative contributions of metabolic and perfusion effects to PID-associated infarct expansion during middle cerebral artery (MCA) occlusion in the Spontaneously Hypertensive Rat. The initial distribution of ischemic depolarization (ID) was established within minutes after MCA occlusion at a cerebral blood flow threshold of ∼40 mL/100 g per minute, with expansion of the depolarized territory during 3 hours detected in half of the animals. Peri-infarct depolarizations were associated with transient metabolic responses, comparable to those observed after spreading depression, with no evidence of cumulative energy failure after multiple transient depolarizations during 1 hour. Speckle contrast imaging of PID-associated flow transients documented prominent distal hyperemic flow responses that became progressively attenuated in regions of already impaired perfusion, with modest propagated flow decreases more proximal to the ischemic core. However, sporadic PIDs were associated with persistent decrements in perfusion, increasing tissue volume below the threshold for energy failure, ID and infarction. These latter, comparatively rare, events can account for the pattern of stepwise infarct expansion in this model.
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takeda
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Michael
authors.initials: M
authors.lastname: Jacewicz
authors.forename: William A
authors.initials: WA
authors.lastname: Pulsinelli
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Nowak
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation; D054022:Cerebrum / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D013181:Cortical Spreading Depression; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR