Acute functional recovery of cerebral blood flow following forebrain ischemia in the rat

Chao Zhou, Tomakazu Shimazu, Turgut Durduran, Daniel Y. Kimberg, Guoqiang Yu, Xiao Han Chen, John A. Detre, Arjun G. Yodh, Joel H. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Following complete cerebral ischemia the post-ischemic blood flow response to functional activation is severely attenuated for several hours. However, little is know about the spatial and temporal extent of the blood flow response in the acute post-ischemic period following incomplete cerebral ischemia. Methods: We used laser speckle flowmetry, which provides two-dimensional high spatial and temporal resolution blood flow images, to examine the response of relative cerebral blood flow (rCBF) to controlled vibrissae stimulation during the first few hours following temporary incomplete ischemia. Male Sprague-Dawley rats (n=10) were prepared under halothane anesthesia and then switched to α-chloralose. The bone overlying the right somatosensory cortex was thinned for the laser speckle imaging. Prior to ischemia the left vibrissae (B1-3, C1-3, D1-3) were stimulated for 3 sec at 5 Hz every minute over a 10-minute period while the rCBF data was collected every 200 msec. Fifteen minutes of transient forebrain ischemia was induced by bilateral carotid arterial occlusion along with controlled hypotension (mean arterial blood pressure lowered to 45-50 mmHg by slowly withdrawing blood from a femoral arterial catheter). This reduced cerebral blood flow to 6.6±1.8% (mean±SE) of the pre-ischemic level. The shed blood was re-infused, the carotid ties were released, and the rCBF response to vibrissae stimulation was repeated at 20, 30, 60, 120, and 180 mins after the end of the ischemia. rCBF images were analyzed using a modified general linear model (GLM) with VoxBo (www.voxbo.org). Statistical maps from the analysis were used to determine the spatial extents of the activation at different time points with a fixed Bonferroni-corrected threshold (pth=0.01). Results: The activation area was significantly reduced 20 mins into reperfusion compared to prior to ischemia (49±12%, p<0.01), and recovered to 77±17% at 2 hours (p=0.36, Figure.1.A). The maximum rCBF response in the activation area determined from the statistical analysis did not change significantly up to three hours post ischemia [ΔrCBF=10.6±0.8% (pre-ischemia); 9.0±0.3% (20 min, p=0.06); 11.1±0.7% (3 hrs, p=0.62)]. However, the time when rCBF reached maximum was significantly delayed from 2.4±0.2 sec prior to ischemia to 3.6±0.1 sec at 20 mins into reperfusion (p<0.001); the delay was reduced to 3.0±0.2 sec after 3 hours, which was still significantly greater than that observed prior to the insult (p<0.05, Figure.1.B). Conclusions: We have incorporated the GLM method into laser speckle imaging, and showed that although the magnitude of the response to functional stimulation was preserved in the early hours following incomplete cerebral ischemia, the area of activation and the temporal response to activation were significantly altered.

Original languageEnglish
Pages (from-to)BO03-05
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
StatePublished - Nov 13 2007

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