Acute functional recovery of cerebral blood flow after forebrain ischemia in rat

Abstract

After complete cerebral ischemia, the postischemic blood flow response to functional activation is severely attenuated for several hours. However, little is known about the spatial and temporal extent of the blood flow response in the acute postischemic period after incomplete cerebral ischemia. To investigate the relative cerebral blood flow (rCBF) response in the somatosensory cortex of rat to controlled vibrissae stimulation after transient incomplete ischemia (15-min bilateral common carotid artery occlusion+hypotension), we employed laser speckle imaging combined with statistical parametric mapping. We found that the ischemic insult had a significant impact on the baseline blood flow (P<0.005) and the activation area in response to functional stimulation was significantly reduced after ischemia (P<0.005). The maximum rCBF response in the activation area determined from the statistical analysis did not change significantly up to 3 h after ischemia (P>0.1). However, the time when rCBF response reached its maximum was significantly delayed (P<0.0001) from 2.4+/-0.2 secs before ischemia to 3.6+/-0.1 secs at 20 mins into reperfusion (P<0.001); the delay was reduced gradually to 2.9+/-0.2 secs after 3 h, which was still significantly greater than that observed before the insult (P=0.04).

Figure 1

Average relative cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) measured during incomplete ischemia (N = 10).

Figure 2

Baseline cerebral blood flow (CBF) changes before and after ischemic insults. Symbols indicate significant difference from preischemic values (P < 0.05).

Figure 3

Images from a representative animal showing functional activations before and after ischemic insult. (A) Peak ΔrCBF images with whisker barrels superimposed. Blood flow response covers a larger region on the brain compared with the whisker barrels. (B and C) Statistical parametric maps from the general linear model analysis showing the activation area at different threshold levels; panel B: p_th = 0.05 and panel C: p_th = 0.01. Black and white background, vasculature map; pseudo-color foreground, activation area; rCBF, relative cerebral blood flow.

Figure 4

Activation area before and after ischemic insult (N = 10). Activation area decreased significantly at 20 mins, 30 mins, 1 h, and 3 h after reperfusion (P < 0.05), but no significant decreases were observed at the 2 h time point. Symbols indicate significant difference from preischemic values (P < 0.05).

Figure 5

Average ΔrCBF curves in response to stimulation before and after ischemic insult from all animals (N = 10). Regions of interest were chosen for each time point based on the general linear model analysis (p_th = 0.01). rCBF, relative cerebral blood flow.

Figure 6

(A) Peak ΔrCBF response before and after ischemic insult (N = 10). Peak ΔrCBF response to the stimulation was not significantly influenced by the ischemic insult (P = 0.14 and 0.18 for p_th = 0.01 and 0.05, respectively). (B) Time to peak ΔrCBF response increased significantly after reperfusion (P < 0.0001 for both thresholds) and recovered slowly toward the preischemic value (N = 10). Symbols indicate significant difference from preischemic values (P < 0.05). rCBF, relative cerebral blood flow.

Figure 7

Peak ΔrCBF (A) and time to peak ΔrCBF (B) responses before and after ischemic insult (N = 10) using a fixed preischemic region of interest (p_th = 0.01 and 0.05, respectively). Symbols indicate significant difference from preischemic values (P < 0.05). rCBF, relative cerebral blood flow.