Functional Reactivity of Cerebral Capillaries

Abstract

The spatiotemporal evolution of cerebral microcirculatory adjustments to functional brain stimulation is the fundamental determinant of the functional specificity of hemodynamically weighted neuroimaging signals. Very little data, however, exist on the functional reactivity of capillaries, the vessels most proximal to the activated neuronal population. Here, we used two-photon laser scanning microscopy, in combination with intracranial electrophysiology and intravital video microscopy, to explore the changes in cortical hemodynamics, at the level of individual capillaries, in response to steady-state forepaw stimulation in an anesthetized rodent model. Overall, the microcirculatory response to functional stimulation was characterized by a pronounced decrease in vascular transit times (20%+/-8%), a dilatation of the capillary bed (10.9%+/-1.2%), and significant increases in red blood cell speed (33.0%+/-7.7%) and flux (19.5%+/-6.2%). Capillaries dilated more than the medium-caliber vessels, indicating a decreased heterogeneity in vessel volumes and increased blood flow-carrying capacity during neuronal activation relative to baseline. Capillary dilatation accounted for an estimated approximately 18% of the total change in the focal cerebral blood volume. In support of a capacity for focal redistribution of microvascular flow and volume, significant, though less frequent, local stimulation-induced decreases in capillary volume and erythrocyte speed and flux also occurred. The present findings provide further evidence of a strong functional reactivity of cerebral capillaries and underscore the importance of changes in the capillary geometry in the hemodynamic response to neuronal activation.

Microvascular Sprouting, Extension, and Creation of New Capillary Connections with Adaptation of the Neighboring Astrocytes in Adult Mouse Cortex under Chronic Hypoxia

“…31) and 3.7 to 4.1 mm (ref. 32) under normocapinia to hypercapnia, respectively. Therefore, we considered these effects of the hypoventilation were minimal in our experimental conditions.…”

“…A closed cranial window provided consistent microvessel and astrocyte structures over 2 to 7 weeks after the surgical procedures under normoxia conditions, 21 indicating the minimum effects because of inflammation resulting from the craniotomy. Previous studies for vasodilation to transient hypercapnia 31,32 and neural activation 33,34 showed that the diameter of the parenchymal capillary was relatively stable, with at most a 10% change. Thus, the mechanism of vasodilation induced through chronic hypoxia differs from the previously known responses.…”

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

“…Several authors have noted a significant capillary vasodilation (Villringer et al, 1994;Hutchinson et al, 2006;Vanzetta et al, 2005;Stefanovic et al, 2008). As pointed out by Stefanovic et al (2008), in the more recent of these studies, "very little data, however, exist on the functional reactivity of capillaries."…”

“…As pointed out by Stefanovic et al (2008), in the more recent of these studies, "very little data, however, exist on the functional reactivity of capillaries." Using two-photon laser scanning microscopy, these authors estimated the contribution of the capillaries to the total stimulation-induced CBV changes and concluded that less than 1/5 (~18%) of the total blood volume increase is occurring on the level of capillaries.…”

Detailed view on slow sinusoidal, hemodynamic oscillations on the human brain cortex by Fourier transforming oxy/deoxy hyperspectral images

“…The notion of a propagating hemodynamic wave, however, can be substantiated by the observation that the estimated wavefront velocities are in line with capillary blood velocities in rodents, i.e. in the order of 1 mm/s (Stefanovic et al, 2008). …”