Transient middle cerebral artery occlusion by intraluminal suture: I. Three-dimensional autoradiographic image-analysis of local cerebral glucose metabolism blood flow interrelationships during ischemia and early recirculation

Ludmila Belayev, Weizhao Zhao, Raul Busto, Myron D. Ginsberg

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Using autoradiographic image-averaging strategies, we studied die relationship between local glucose utilization (LCMRglc) and blood flow (LCBF) in a highly reproducible model of transient (2-hour) middle cerebral artery occlusion (MCAO) produced in Sprague-Dawley rats by insertion of an intraluminal suture coated with poly-L-lysine. Neurobehavioral examination at 60 minutes after occlusion substantiated a high-grade deficit in all animals. In two subgroups, LCBF was measured with 14C-iodoantipyrine at either 1.5 hours of MCAO, or at 1 hour of recirculation after suture removal. In two other matched subgroups, LCMRglc was measured with 14C-2-deoxyglucose at 1.5 to 2.25 hours of MCAO, and at 0.75 to 1.5 hours of recirculation after 2 hours of MCAO. Average image data sets were generated for LCBF, LCMRglc, and the LCMRglc/LCBF ratio for each study time. Middle cerebral artery occlusion for 2 hours induced graded LCBF decrements affecting ipsilateral cortical and basal ganglionic regions. After 1 hour of recirculation, LCBF in previously ischemic neocortical regions increase by 40% to 200% above ischemic levels, but remained depressed, on average, at about 40% of control. By contrast, frank hyperemia was noted in the previously ischemic caudoputamen. Mean cortical LCBF values during MCAO correlated highly with their respective LCBF values after 1 hour of recirculation (R = 0.93), suggesting that post- ischemic LCBF recovery is related to the depth of ischemia. Despite focal ischemia, LCMRglc during ~2 hours of MCAO was preserved, on average, at near-normal levels; but following ~1 h of recirculation, LCMRglc became markedly depressed (on average, 55% of control in previously densely ischemic cortical regions). Regression analysis indicated that this depressed glucose utilization was determined largely by the intensity of antecedent ischemia. By pixel analysis, the ischemic core (defined as LCBF 0% to 20% of control) comprised 33% of the ischemic hemisphere, and the penumbra (LCBF 20% to 40%) accounted for 26%. The penumbra was concentrated at the coronal poles of the ischemic lesion and formed a thin shell around the central ischemic core. During 2 hours of MCAO, the LCMRglc/LCBF ratio within the ischemic penumbra was increased four-fold above normal (average, 179 umol/100 mL). In marked contrast, after ~1 h recirculation, this uncoupling had almost completely subsided. The companion study (Zhao et al, 1997) further analyzes these findings in relation to patterns of infarctive histopathology.

Original languageEnglish (US)
Pages (from-to)1266-1280
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume17
Issue number12
DOIs
StatePublished - Dec 1997

Keywords

  • 2-deoxyglucose
  • Cerebral blood flow
  • Flow-metabolism couple
  • Focal cerebral ischemia
  • Penumbra
  • Stroke

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

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