Morphological changes in capillaries in the ischemic brain in Wistar rats

Abstract

The microvasculature in the brain plays a vital role in the maintenance of brain perfusion, and fulfills the dynamic requirements of normal brain functions. It is well known that collateral circulation can be induced by ischemia in cerebral infarctions, but it is not known whether cerebral ischemia affects microvasculatures in the ischemic region. In the present study, we examined quantitatively serial changes in capillaries following bilateral common carotid artery ligation in Wistar rats. After the animals were perfused with tetramethylrhodamine isothiocyanate-labeled gelatin 3 h (n = 9), 1 day (n = 9), 7 days (n = 9) and 28 days (n = 9) after the ligation, capillary diameters in the brain sections were measured with a confocal laser-scanning microscope. Capillary diameters of the cerebellum did not differ among all groups, while those in the ischemic regions decreased significantly 3h after the ligation (p<0.01), thereafter gradually returned toward the baseline level, and became significantly larger (168% of the control) 28 days after the ligation (p< 0.01). The density of capillaries in the frontal and parietal cortices increased approximately to 1.3-fold of those of the control level 28 days after the ligation. Transmission electron microscopy showed that the mean ratio of the inner diameter to the outer diameter of capillaries in the frontal cortex became significantly greater 28 days after the ligation (p<0.05). Our data indicate that capillaries dilate in the ischemic brain region in the chronic phase of cerebral ischemia. It is also suggested that neovascularization occurs in the ischemic brain region.

Delayed histochemical alterations within the neurovascular unit due to transient focal cerebral ischemia and experimental treatment with neurotrophic factors

“…While focusing on morphological alterations due to the ischemic stimulus, we observed–at least in part–thinned endothelia, which is in line with findings from Taguchi et al [40] and Morris et al [41]. These authors had demonstrated a decreased diameter of ischemia-affected capillaries and microvessels in diverse brain regions following global brain ischemia.…”

Mean microvessel segment length and radius after embolic stroke: Comparison of magnetic resonance imaging (MRI) and laser scanning confocal microscopy (LSCM)

“…When MRI was performed 6 weeks after MCA occlusion, the VSI data showed that the vessels in the recovery region were significantly larger in diameter compared with homologous tissue in the contralateral hemisphere, and this was confirmed by LSCM 3D quantitative analysis. (Taguchi et al, 2004) reported that capillary diameter at the ischemic boundary became greatly enlarged by 4 weeks after occlusion, which seems to indicate that the interface between blood and neural tissues becomes thin and wide, which would be beneficial for exchanging substances between circulating blood and the ischemic tissue. We found that MRI and LSCM measurements of both VSI and MSL showed a strong correlation between the recovery region and normal contralateral tissue.…”

Capillary Remodeling and Collateral Growth Without Angiogenesis After Unilateral Common Carotid Artery Occlusion in Mice

“…Previously, cerebral ischemia [17,26,32] as well as cerebral hypoxia [13] was reported to trigger angiogenesis. In these previous papers, angiogenesis was assessed by counting capillaries only in fixed brain tissue.…”

“…The morphological changes in capillaries, as well as increases in capillary density, have been reported in some brain ischemia models [19,26]. These reports are based on histological examination of fixed brain tissue, where vessel diameter can readily change during perfusion–fixation process.…”

“…Densitometry (computerized analysis of marker‐positive capillaries) was often used to calculate capillary density in previous studies [11,13], where increase in capillary diameter and tortuous deformity may result in excessive counting of partially sectioned capillaries or apparent increase in marker‐positive area. When capillaries dilate to the size of an arteriole [26], arterioles may be mistakenly counted as capillaries, resulting in apparent increase in capillary density. In addition, variation in capillary density within the affected brain and among individual animals may easily result in bias in counting.…”