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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 0.1). 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).

It has been suggested that antihypertensive drug therapy is attributable to the lower blood pressure variability, we investigated the effects of 4 classes of antihypertensives on the blood pressure variability; in addition, we also compared the effects among 4 calcium channel blockers.We measured the 24-hour blood pressure variability in 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, β blocker, or calcium channel blocker.The daytime blood pressure variability treated with β blockers (14.3 ± 3.1) was higher than that treated with an angiotensin receptor blockers (11.5 ± 3.1) or calcium channel blockers (12.6 ± 3.4) in patients with cerebrovascular disease (P.05). In the analysis of the patient distribution of blood pressure variability, patients receiving β blockers occurred more frequently in the higher blood pressure variability (P = .0023). Treatment with angiotensin receptor blockers and cilnidipine, which blocks N-type calcium channels, was shown to be more frequently associated with the lower blood pressure variability (P = .0202 and .0467). The mean blood pressure of patients grouped by distribution of blood pressure variability was found to be independent to blood pressure variability, for any of the antihypertensive drugs or calcium channel blockers examined.From the results, it is suggested that angiotensin receptor blocker and calcium channel blockers rather than β blockers may be more favorable for blood pressure management in patients with cerebrovascular disease. Among the calcium channel blockers, cilnidipine may be more favorable than other calcium channel blockers.

Background and Purpose— Functional stimulation is accompanied by increases in regional cerebral blood flow which exceed metabolic demands under normal circumstances, but it is unknown whether functional stimulation is beneficial or detrimental in the setting of acute ischemia. The aim of this study was to determine the effect of forepaw stimulation during temporary focal ischemia on neurological and tissue outcome in a rat model of reversible focal forebrain ischemia. Methods— Sprague-Dawley rats were prepared for temporary occlusion of the right middle cerebral artery (MCA) using the filament model. Cerebral blood flow in the MCA territory was continuously monitored with a laser-Doppler flowmeter. Subdermal electrodes were inserted into the dorsal forepaw to stimulate either the forepaw ipsilateral or contralateral to the occlusion starting 1 minute into ischemia and continuing throughout the ischemic period. A neurological evaluation was undertaken after 24 hours of reperfusion, and animals were then euthanized and brain slices stained with 2,3,5-triphenyltetrazolium chloride. Cortical and striatal damage was measured separately. Results— The cortical and striatal infarct volumes were both significantly reduced in the contralateral stimulated group compared with the ipsilateral stimulated group (48% total reduction). There were no statistically significant differences in the neurobehavioral scores between the 2 groups, or in the laser-Doppler flow measurements from the MCA core. Conclusions— Functional stimulation of ischemic tissue may decrease tissue damage and improve outcome from stroke. Although the precise mechanism of this effect remains to be determined, functional stimulation could readily be translated to clinical practice.

Background and Purpose— Activators of peroxisome proliferator-activated receptor-γ (PPARγ), a member of the PPAR family, increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting a mechanism by which it may exert its protective effect within the brain. These properties raise the question of whether a PPARγ agonist may be neuroprotective in models of ischemia without reperfusion, in which oxidative injury is less prevalent. Methods— In 2 groups of rats, 90 minutes of middle cerebral artery (MCA) occlusion was followed by 1 day of reperfusion, with 1 group receiving pioglitazone (a PPARγ agonist) starting 72 hours before MCA occlusion (MCAO) and continuing through the day of occlusion, whereas the other group received vehicle only. In 2 comparable groups, the MCA was occluded permanently. One day after occlusion, the animals were tested neurologically and infarct volumes were calculated. In a separate group, rats were treated with pioglitazone or vehicle for 4 days. Tissue was obtained from the cortex and the striatum 2 hours into reperfusion after 90 minutes of MCAO, and the tissue was examined for CuZn-SOD by Western blot. Results— Results show a significant reduction in infarct size in the treated rats, with transient MCAO but not permanent MCAO. There was also an improvement in neurological score in the treated animals after transient MCAO. The level of CuZn-SOD was increased in the cortex in treated animals. Conclusions— These data, which show that a PPARγ agonist reduces infarct size in transient but not permanent MCAO, suggest that the role of PPARγ is specific to events occurring during reperfusion. Our data point to CuZn-SOD as the mediator of this neuroprotection.

Adrenomedullin(AM)is a vasodilatory hormone secreted mainly by the vascular wall, and its expression is remarkably enhanced after stroke. Several studies have shown that AM inhibits ischemic injury in the brain. The present study investigates the effects of AM on nitric oxide(NO)production during forebrain ischemia and reperfusion. Halothane anesthesia was administered to AM-knockout(AM )and control(C57 BL 6J)mice and then NO production was continuously monitored in the left striatum by in vivo microdialysis. A laser Doppler probe was fixed on the right scalp to measure relative cerebral blood flow(rCBF)continuously. Blood pressure(BP), blood gases and body temperature were monitored and physiologically maintained. After equilibrium for 2 hours, fractions were collected every 10 minutes. Forebrain cerebral ischemia was produced by occluding both common carotid arteries. After 10 minutes, the loops around both common carotid arteries were released. Levels of nitrite and nitrate in dialysates were determined using the Griess reaction. At 6 hours after forebrain cerebral ischemia, the degrees of the ischemic damage in hippocampal CA1 neurons were investigated. Knockout of the AM gene did not affect BP and rCBF. Levels of total NO(nitrite+nitrate) were lower in AM-knockout mice at baseline, during ischemia and after reperfusion. The survival cell rate of hippocampal CA1 neurons in AM-knockout mice was lower than that of control mice. These data suggest that AM exert protective effects by activating NO synthase in the brain during ischemia and reperfusion. (Cerebral Blood Flow and Metabolism 21:1―6,2010)