Acute Carotid Occlusion Alters the Activation Flow Coupling Response to Forepaw Stimulation in a Rat Model

Abstract

Background and Purpose-To determine whether the hemodynamic response to functional stimulation is sensitive to proximal arterial occlusion, we measured the activation flow coupling response in a rat model of acute reversible vascular occlusion. Methods-In ␣-chloralose-anesthetized rats (nϭ18), laser Doppler measurements were made through a thinned skull over the somatosensory cortex in response to electrical forepaw stimulation. Signal-averaged responses to 4 and 8 seconds of electrical forepaw stimulation were obtained before, during, and shortly after acute unilateral or bilateral carotid occlusion produced with the use of a surgically placed snare. Results-Baseline cerebral blood flow was significantly decreased over the forepaw region of the somatosensory cortex after both occlusion of the carotid contralateral to the stimulated forepaw and bilateral occlusion compared with preocclusion (PϽ0.05). Postocclusion and ipsilateral occlusion led to a nonsignificant increase in baseline cerebral blood flow compared with preocclusion. Contralateral carotid occlusion and bilateral occlusion significantly prolonged the temporal characteristics of the flow response, especially the delay to peak (PϽ0.05), compared with preocclusion, whereas ipsilateral carotid occlusion significantly shortened the delay to peak (PϽ0.05). Only contralateral carotid occlusion produced a significant reduction in the peak amplitude of the flow response compared with preocclusion (PϽ0.05). Key Words: carotid artery occlusion Ⅲ cerebral blood flow Ⅲ cerebrovascular circulation Ⅲ rats A ctivation flow coupling (AFC), which is the coupling of cerebral blood flow (CBF) with neuronal activity, is the basis for many functional neuroimaging techniques. A variety of techniques, including optical imaging, 1,2 near-infrared spectroscopy, 3 video microscopy, 4,5 and laser Doppler (LD) flowmetry, 6 -11 have been used to determine the spatial and temporal characteristics of the AFC response in animal models under normal conditions. However, the influence of pathophysiological alterations on AFC remains poorly understood. Conclusions-ThesePrevious studies that have examined the effects of proximal carotid occlusion on resting CBF have demonstrated that acute carotid occlusion leads to a decrease in blood flow in the hemisphere of the occluded side. 12,13 However, with chronic occlusion, baseline flow returns to preoccluded values within a few days. 12 Two studies investigated the effects of transient severe global ischemia (4-vessel occlusion) and reperfusion on the AFC response. Dietrich et al 14 reported that functional activation due to whisker stimulation in the rat was reduced for up to 5 days after 4-vessel occlusion, whereas Ueki et al 15 demonstrated that 30 minutes after See Editorial Comment, page 960severe forebrain ischemia, the functional activation response was almost completely suppressed, although evoked potentials were present. No studies in animals have investigated the AFC response during mild ischemia induced by acute unilateral or bi...

Acute Functional Recovery of Cerebral Blood Flow after Forebrain Ischemia in Rat

“…previously observed a prolonged time to peak after unilateral carotid occlusion and attributed the delay to the use of a circuitous recruitment of collateral supply (Ances et al, 2000). However, in the present study, the carotids were reopened, suggesting that the observed delay may represent an alteration in activation flow coupling after the ischemic insult.…”

“…There has been considerable interest in the ability of the cerebrovasculature to respond to functional stimulation after a period of transient cerebral ischemia (Schmitz et al, 1997(Schmitz et al, , 1998Ueki et al, 1988;Ances et al, 2000;Dijkhuizen et al, 2003), which may provide a window into the eventual fate of the tissue. Better characterization of these responses after ischemia could also be important for interpreting studies of functional reorganization after ischemic injury.…”

Altered Hemodynamics and Regional Cerebral Blood Flow in Patients With Hemodynamically Significant Stenoses

“…A similar effect was observed in a previous animal study showing a delay in the time-to-peak flow response in a rat model with acute carotid occlusion. 22 In addition to changes in temporal dynamics of the BOLD response, we observed an increase in the magnitude of an early negative response in left primary motor cortex, which is within the vascular region that was consistently impaired in our group of patients. The present results are similar to a case study of an asymptomatic patient with bilateral carotid stenosis except in duration of the initial dip.…”

“…In the event-related condition, there were no significant performance differences between the 2 groups in the reaction time of both hands (patients 0.52Ϯ0.04; controls 0.44Ϯ0.03 s; unpaired t test; Pϭ0.1) and mean squeeze pressure of both hands (patients 22 …”

Altered Hemodynamic Responses in Patients After Subcortical Stroke Measured by Functional MRI

“…For example, duplex Doppler studies, which reflect global perfusion changes in both gray and white matter, have shown decreased microvascular reactivity in patients with subcortical, white matter lesions. 32 Patients with chronic hypertension or diabetes mellitus (another cause of microvascular pathology in the brain) show similar differences in acetazolamideor CO 2 -induced reactivity relative to healthy controls. 33,34 Nonetheless, interpretation of these data should be regarded as only preliminary.…”