Microvessel Diameter Research Articles

30 Evolution of cerebrovascular changes in mouse cortex during normal pregnancy by in vivo two-photon imaging

Introduction Past studies have shown that cerebral autoregulation is a physiologic process that maintains blood flow at an appropriate level. Impairment of cerebral autoregulation during pregnancy may contribute to further diseases like preeclampsia and eclampsia. However, little is known about the normative cerebrovascular adaptation during pregnancy. Objectives In the present study we observed adaptive changes in the blood flow and vessel diameter from prepregnancy to late pregnancy by in vivo two-photon imaging. Methods 12 female C57 mice were randomly divided into four groups: non-pregnancy, early-pregnancy, middle-pregnancy, late pregnancy. After the animals were anesthetized, a mouse head holder was used to hold the head. A thinned skull window was made (1–2 mm in diameter) over the motor cortex. One day later, Rhodamin B dissolved in saline (3 mg/ml, 0.2 ml/20 kg) was injected intraperitoneally to label the vessels 15 min before beginning the imaging experiments. The animal was anesthetized and placed under two photon microscope to observe; blood flow signal pictures were taken using line-scan and analyzed by blood flow analysis software programmed. Results The blood flow velocity of arteriovenous vessels and capillaries increased significantly in middle and late pregnancy compared to non-pregnancy and early-pregnancy; vascular diameters in middle and late pregnancy also became bigger than that in non-pregnancy and early-pregnancy. Conclusions Both the blood flow velocity and diameter of cortical micro vessels increased significantly from non-pregnancy and early-pregnancy to middle and late pregnancy. Such results demonstrated a progressive cerebrovascular adaptation from prepregnancy to late pregnancy.

Hypoxia inducible factor and microvessels in peri-implantation endometrium of women with recurrent miscarriage

To compare the expression of hypoxia inducible factor 1α (HIF1α) and micro-blood vessels in endometrium around the time of embryo implantation in women with recurrent miscarriage and fertile controls. Retrospective study. University hospitals. Sixty women: 24 with recurrent miscarriage and 36 with proven fertility. Endometrial biopsy samples obtained precisely 7days after luteinization hormone (LH) surge in a natural cycle. Immunohistochemical analysis to determine expression of HIF1α and micro-blood vessels as identified by von Willebrand factor (vWF) in endometrium; semiquantitative analysis using H-score analysis of staining intensity for HIF1α in the luminal epithelium, glandular epithelium, and stroma, separately; number, diameter, and volume of vWF-positive endometrial micro-vessels as counted by Image J software. The luminal epithelial and stromal expression of HIF1α in women with recurrent miscarriage was higher than found in the fertile controls, with the change in the luminal epithelium reaching the highest statistical significance. There was no statistically significant difference in HIF1α expression in glandular epithelium between the two groups. An increased number as well as volume of micro-blood vessels was observed in women with recurrent miscarriage although the mean diameter of the micro-blood vessels did not statistically significantly differ between the two groups. We have found an aberrant expression of HIF1α and micro-vessel number and volume in the peri-implantation endometrium of women with recurrent miscarriage, suggesting that altered hypoxia and vascularization status may account for the endometrial contribution to recurrent miscarriage.

Hemoglobin induced NO/cGMP suppression Deteriorate Microcirculation via Pericyte Phenotype Transformation after Subarachnoid Hemorrhage in Rats.

Subarachnoid hemorrhage (SAH) usually results from ruptured aneurysm, but how leaked hemoglobin regulates the microcirculation in the pathophysiology of early brain injury after SAH is still unclear. In the present study, we sought to investigate the role and possible mechanism of hemoglobin induced pericyte phenotype transformation in the regulation of microcirculation after SAH. Endovascular perforation SAH rat model, brain slices and cultured pericytes were used, and intervened with endothelial nitric oxide synthase (eNOS) antagonist L-NNA and its agonist scutellarin, hemoglobin, DETA/NO (nitric oxide(NO) donor), PITO (NO scavenger), 8-Br-cGMP (cGMP analog). We found modulating eNOS regulated pericyte α-SMA phenotype transformation, microcirculation, and neurological function in SAH rats. Modulating eNOS also affected eNOS expression, eNOS activity and NO availability after SAH. In addition, we showed hemoglobins penetrated into brain parenchyma after SAH. And hemoglobins significantly reduced the microvessel diameters at pericyte sites, due to the effects of hemoglobin inducing α-SMA expressions in cultured pericytes and brain slices via inhibiting NO/cGMP pathway. In conclusion, pericyte α-SMA phenotype mediates acute microvessel constriction after SAH possibly by hemoglobin suppressing NO/cGMP signaling pathway. Therefore, by targeting the eNOS and pericyte α-SMA phenotype, our present data may shed new light on the management of SAH patients.

Abstract TMP108: Absence of Cortical Microvessel Spasm During Large Vessel Spasm Following Experimental Subarachnoid Hemorrhage

Introduction: A significant portion of the morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH) is due to delayed ischemic neurological deficits (DIND). Although large vessel vasospasm has been implicated as a cause of DIND, the presence of such spasm is not always correlated with DIND. In the present experiment we examined the cortical microvasculature in awake mice after SAH in an experimental model typically associated with large vessel vasospasm. Methods: Twenty adult mice underwent cisterna magna (CM) injection of 60ul syngenic donor blood or artificial cerebrospinal fluid (aCSF). The mice were perfused at 72 hours, and Circle of Willis (COW) vessel diameters were measured. In a separate experiment, polished and reinforced thinned skull cranial windows were created in 10 mice that then underwent CM blood or aCSF injection. Cortical microvessels were measured in living, awake mice in the postoperative vasospasm period using two photon laser scanning microscopy. Results: A pairwise comparison of COW vessels revealed a statistically significant difference in vessel diameter between the experimental and control groups at each of the sites measured (ACA, P=0.0012; MCA, P=0.0259; Pcom, P=0.0053). In the second experiment, there were no significant differences in cortical microvessel diameter between the experimental and control groups. Conclusions: This study represents the first report of in vivo imaging of cortical microvessels during large vessel spasm following SAH. In a CM injection SAH model, we observed significant large vessel spasm but no cortical microvessel spasm. These results may have important implications for understanding the mechanisms of DIND.

Clinicopathological, endoscopic, and molecular characteristics of the "skirt" - a new entity of lesions at the margin of laterally spreading tumors.

A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt. Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes. A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt. The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt.

Correlation of axial blood velocity to venular and arteriolar diameter in the human eye in vivo

The axial blood velocity (Vax) association with microvessel diameter (D) was studied at 104 different postcapillary venules (4 μm < D < 24 μm) and 30 different precapillary arterioles (6 μm≤D≤12 μm) in the human conjunctiva of normal healthy humans. Venular diameter sizes were classified as "very small" (Group 1, 4.4 μm≤D < 8.9 μm), "small" (Group 2, 8.9 μm≤D < 13.8 μm), "medium" (Group 3, 13.8 μm≤D < 19.1 μm) and "large" (Group 4, 19.1 μm≤D≤23.5). The Spearman's correlation coefficient (rs) in all 4 venular groups was less than 0.36 and not statistically significant (n = 26, p≥0.08). Similar correlation results were observed for the arteriolar group (rs) ≈ 0) for the peak systolic, the average and the end systolic axial velocities. Vax was significantly (p < 0.001) lower in Group 1 in comparison to that in Group 2 and significantly (p < 0.01) lower in Group 2 in comparison to that in Group 3. However, Vax was not significantly lower in Group 3 in comparison to that in Group 4. Average Vax and standard deviation was 0.48 ± 0.13, 0.64 ± 0.16, 0.82 ± 0.25 and 0.88 ± 0.32 mm/s for Groups 1, 2, 3 and 4 respectively. The above results reinforce the importance of measuring D in microvascular hemodynamics. Higher diameters suggest higher axial velocities but Vax does not change significantly within the limits of each of the aforementioned groups.

Influence of smoking cessation on the microcirculatory bed in apparently healthy young people

To study the influence of smoking cessation on the microcirculatory bed (MCB) in 33 healthy young people. The investigation enrolled 33 healthy young people (male/female (M/F) ratio, 20:13; mean age, 21.6±0.5 years) who had quit smoking 1 month to 10 years (mean age 2.5±0.5 years) before. Comparable groups consisted of 15 smokers (M/F ratio, 5:10; mean age, 21.5±0.8 years) and 18 nonsmokers (M/F ratio, 6:12; mean age, 21±0.3 years). Computer-assisted video-biomicroscopy of the bulbar conjunctiva was carried out. When assessing the attention was focused on microvessel diameter changes in the patients who had quit smoking compared to the smokers and nonsmokers. As compared to the smokers, those who had quit smoking showed a significant increase in the mean diameters of arterioles (13.01±0.41 and 18.33±0.65 µm; р<0.001) and capillaries (9.2±0.23 and 9.89±0.19 µm; р<0.05). The number of functioning capillaries per mm2 of the conjunctival surface did not differ from that in the nonsmokers (8.01±0.21 and 8.25±0.44; р>0.05). Thus, the rarefication phenomenon reflecting the influence of smoking on the MCB vessels at a young age undergoes rapidly regression. There are increases in the diameter of arterioles and the number of functioning capillaries just in the first months of smoking cessation (р<0.01). The considerably increased diameters of arterioles and capillaries and the larger number of functioning capillaries per mm2 of the conjunctival surface suggest that smoking cessation at a young age have a positive impact on MCB vessels.

Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle

Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site-specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4-fold increase in its perfusion as well as a 2- to 4-fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By transdermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels.

Relationship between the Extent of Morphological Changes in the Brain and Blood and Urine Ethanol Concentrations

Regression analysis of the connections between changes in histological brain structures (neurons, neuroglia, and microvessels) and the extent of poisoning with ethanol (blood and urine ethanol concentrations) was performed. Specimens were obtained from 40 male and female corpses aged 20–81 years. Decreases in microvessel diameter in the cerebral cortex and cerebellum and increases in microvessel diameter in the white matter, along with increases in the numbers of vessels with stasis, in the numbers of astrocytes with cytoplasmic granularity, and in various signs of cerebral edema, as well as decreases in the numbers of astrocyte processes and the ability of erythrocytes in the stasis zone to stain with glycine cresol stain, were found to correlate with the mean square ethanol concentration (MSEC) in blood and urine. This allows this parameter to be assessed in histological studies of the brain. Conversely, knowledge of MSEC allows the presence of certain histological changes in the brain to be evaluated.

MORPHOMETRIC ANALYSIS OF ESOPHAGEAL CIRCULATORY INTRAORGAN COMPONENT DIAMETERS IN HUMAN FETUSES AND ADULTS

Aim. To carry out morphological analysis of the changes in diameter of fetal and adult intraorgan microvessels of the lower third of esophagus. Materials and methods. Anatomical and histological methods were used to reveal the components of hemomicrocirculatory canal. The lower third of esophagus was studied in 18 human fetuses in the terms of 13, 23, 26, 32, 36 weeks of development, in 7 dead adults aged 41 to 50 years, who did not suffer from esophageal and hepatic diseases in the course of life. Results. Reliable age changes in external diameter of human esophageal arteries, veins, arterioles, capillaries, postcapillaries and venules using nonparametric statistical methods were detected. Conclusions. In dynamics of prenatal development, there occur unequal changes in capillary diameter: increase during the week 23 of gestation (up to 4,98 ± 0,11 mcm, p = 0,005), decrease beginning from the weeks 26 to 32 (4,07 ± 0,14 mcm, p = 0,000) and rise by the week 36 (5,40 ± 0,17 mcm, p = 0,000). Diameter of capillaries of the lower third of esophagus in adults is 9,43 ± 0,24 mcm ( p = 0,000).

Evidence for a Profound Remodeling of Skeletal Muscle and Its Microvasculature in Sickle Cell Anemia

Sickle cell anemia (SCA) is a hemoglobinopathy leading to major hematologic, hemorheologic, and hemodynamic disorders that induce various complications, including organ failure, and ultimately lead to death. Here, we assessed for the first time repercussions of SCA on skeletal muscle and its microvasculature. Twenty-seven sedentary Cameroonian volunteer men participated in the study. They were assigned to one of three groups according to their hemoglobin status (healthy control subjects, n = 10; sickle cell trait carriers, n = 10; and SCA patients, n = 7) and underwent muscle biopsy of the vastus lateralis. SCA was associated with microvessel rarefaction, decrease in capillary tortuosity, and widening of microvessel diameter. The absence of capillary wall reinforcement was shown by lack of wall thickening and lack of fibrous tissue or smooth muscle in their constitution. We also observed changes in fiber type distribution, muscle atrophy, an increase in satellite cell number, and a decrease in activity of creatine kinase and several oxidative enzymes. No signs of tissue necrosis, inflammatory stress, fibrosis, or segmented fibers were observed. The present study highlighted marked effects of SCA on microvascular, structural, and energetic characteristics of skeletal muscle.

Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease.

Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood-brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.

Constriction and dysfunction of pial arterioles after regional hemorrhage in the subarachnoid space

Increasing evidence indicates that poor outcomes after brain hemorrhage, especially after subarachnoid hemorrhage (SAH), can be attributed largely to dysfunction of the cerebral microcirculation. However, the cause of this dysfunction remains unclear. Here, we investigated changes in the cerebral microcirculation after regional hemorrhage in the subarachnoid space using the closed cranial window technique in mice. A single pial arteriole on the surface of the brain was punctured to induce a regional hemorrhage in the subarachnoid space. Physiological parameters were monitored during the procedure, and microvessel diameter was measured after hemorrhage. The vasoreactivity of the arterioles in response to hypercapnia as well as to topical application of the vasodilator acetylcholine (ACh) and S-nitroso-N-acetyl-penicillamine (SNAP) were assessed. The constriction of pial arterioles was detected without changes in other physiological parameters. Decreased reactivity of pial arterioles to all of the applied vasodilatory stimuli was observed after hemorrhage. Our results indicate that regional hemorrhage in the subarachnoid space can induce the vasospasm of microvessels and also reduce the vasoreactivity of pial arterioles.

Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular plasticity in the sensory circumventricular organs of adult mouse brain.

The sensory circumventricular organs (CVOs), which comprise the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO) and the area postrema (AP), lack a typical blood-brain barrier (BBB) and monitor directly blood-derived information to regulate body fluid homeostasis, inflammation, feeding and vomiting. Until now, almost nothing has been documented about vascular features of the sensory CVOs except fenestration of vascular endothelial cells. We therefore examine whether continuous angiogenesis occurs in the sensory CVOs of adult mouse. The angiogenesis-inducing factor vascular endothelial growth factor-A (VEGF-A) and the VEGF-A-regulating transcription factor hypoxia-inducible factor-1α were highly expressed in neurons of the OVLT and SFO and in both neurons and astrocytes of the AP. Expression of the pericyte-regulating factor platelet-derived growth factor B was high in astrocytes of the sensory CVOs. Immunohistochemistry of bromodeoxyuridine and Ki-67, a nuclear protein that is associated with cellular proliferation, revealed active proliferation of endothelial cells. Moreover, immunohistochemistry of caspase-3 and the basement membrane marker laminin showed the presence of apoptosis and sprouting of endothelial cells, respectively. Treatment with the VEGF receptor-associated tyrosine kinase inhibitor AZD2171 significantly reduced proliferation and filopodia sprouting of endothelial cells, as well as the area and diameter of microvessels. The mitotic inhibitor cytosine-b-D-arabinofuranoside reduced proliferation of endothelial cells and the vascular permeability of blood-derived low-molecular-weight molecules without changing vascular area and microvessel diameter. Thus, our data indicate that continuous angiogenesis is dependent on VEGF signaling and responsible for the dynamic plasticity of vascular structure and permeability.

Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy.

This study aimed to examine the cortical microvessel diameter response to hypercapnia in misery perfusion using two-photon laser scanning microscopy (TPLSM). We evaluated whether the vascular response to hypercapnia could represent the cerebrovascular reserve. Cerebral blood flow (CBF) during normocapnia and hypercapnia was measured by laser-Doppler flowmetry through cranial windows in awake C57/BL6 mice before and at 1, 7, 14, and 28 days after unilateral common carotid artery occlusion (UCCAO). Diameters of the cortical microvessels during normocapnia and hypercapnia were also measured by TPLSM. Cerebral blood flow and the vascular response to hypercapnia were decreased after UCCAO. Before UCCAO, vasodilation during hypercapnia was found primarily in arterioles (22.9%±3.5%). At 14 days after UCCAO, arterioles, capillaries, and venules were autoregulatorily dilated by 79.5%±19.7%, 57.2%±32.3%, and 32.0%±10.8%, respectively. At the same time, the diameter response to hypercapnia in arterioles was significantly decreased to 1.9%±1.5%. A significant negative correlation was observed between autoregulatory vasodilation and the diameter response to hypercapnia in arterioles. Our findings indicate that arterioles play main roles in both autoregulatory vasodilation and hypercapnic vasodilation, and that the vascular response to hypercapnia can be used to estimate the cerebrovascular reserve.

Comparative study of 3D reconstruction of rat sciatic nerve microvessels using Evans blue and lead oxide

Background:The blood supply of peripheral nerve grafts is one of the important factors that affect nerve regeneration. Many investigators have studied how intraneural microvessels are distributed and ways to promote the angiogenesis of grafts. However, there still does not exist an ideal intraneural microvascular model. The purpose of this study was to compare the three-dimensional (3D) reconstruction of microvessels of the sciatic nerve in Sprague-Dawley (SD) rats after systemic perfusion with Evans blue (EB) or lead oxide.Methods:Ten adult SD rats were randomized to a fluorography group (EB) or radiography group (lead oxide). After administration of the perfusion agents, imaging information was obtained by fluorescence microscopy and micro-computed tomography (μCT). Three-dimensional reconstruction was performed, and the diameter of microvessels at a constant distance (a cross-section was taken every 1 mm), the vascular index, and volume were measured. Two-dimensional (2D) images were obtained by serial sectioning and μCT scanning using the two methods described.Results:In the EB group, the diameter, vascular area, and vascular index of microvessels were 11·79 ± 7·23 μm, 0.14 ± 0.05 mm2, and 24·19 ± 5·03%, respectively, and in the lead oxide group 26·45 ± 11·81 μm, 0.06 ± 0.02 mm2, and 10·73 ± 2·06%, respectively. Microvessels with diameters <20 μm were visualized better in the EB group than in the lead oxide group (P < 0·01). However, there was no significant difference between the groups in the visualization of microvessels with diameters 20–49 μm (P > 0·05).Conclusions:Both EB and lead oxide can be used for 2D study of intraneural microvessels and 3D observation after reconstruction. Lead oxide is easy to use, and though its resolution is lower than that of EB for smaller microvessels with diameters <20 μm, it is more suitable for studying a large sample volume.

Central versus peripheral blood pressure components as determinants of retinal microvessel diameters

Background: We assessed association of retinal arteriolar and venular diameters with central and peripheral blood pressure (BP).

Orthogonal polarization spectral imaging of conjunctival microcirculation

Orthogonal polarization spectral (OPS) imaging is an optical imaging technique that uses a handheld microscope and green polarized light to visualize the red blood cells in the microcirculation of organ surfaces. The purpose of this study was to evaluate whether OPS imaging can be used for the functional and morphological evaluation of microcirculation in the conjunctiva. To accomplish the aforementioned purpose, 21 eyes of 21 volunteer patients were examined. OPS images of the vasculature of the inferior conjunctiva and the nasal part of the bulbar conjunctiva were taken from each eye. The images were subsequently analyzed using a computer, and the following parameters were assessed: red blood cell velocity, blood vessel diameter, and functional capillary density. In addition, distinct qualitative aspects of the conjunctival microvasculature were characterized. OPS imaging facilitated both the observation of red blood cells that were flowing through conjunctival vessels on a white background, and the measurement of other quantitative and qualitative microvascular parameters. Significant differences between several measures of the inferior and nasal bulbar conjunctival microcirculations were found, including differences in the configurations of the vessel segments, the number of vessel segments, the number of bifurcations, the mean diffusion distance, and the functional capillary density. OPS imaging can be used to measure the diameters of microvessels, functional capillary density, and other parameters. Significant differences between the microcirculations of the inferior conjunctiva and the nasal bulbar conjunctiva were found, which indicates the necessity of using a standardized approach to examine the conjunctival vasculature. OPS imaging is suitable for both the functional and morphological evaluation of the conjunctival microcirculation.

Morphometry of the hippocampal microvasculature in post‐stroke and age‐related dementias

BackgroundOptimal vascular function is vital for prevention of dementia. We hypothesized that elderly post-stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia.MethodsUsing stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post-stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell α-actin (SMA).ResultsWe found increased Lv of both GLUT1 and COL4 immunostained microvessels (P < 0.05) in the hippocampal CA1 region of post-stroke demented (PSD) and AD cases compared with post-stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12 μm.ConclusionsAn increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia.

Central vs. peripheral blood pressure components as determinants of retinal microvessel diameters

BackgroundWe assessed association of retinal arteriolar and venular diameters with central and peripheral blood pressure (BP). MethodsWe post-processed retinal photographs from 514 participants randomly recruited from a Flemish population (mean age, 50.6 years; 50.8% women), using IVAN software to generate retinal arteriolar (CRAE) and venular (CRVE) equivalents. We measured peripheral BP by mercury sphygmomanometry and central BP by tonometry at the carotid artery. We applied multivariable-adjusted regression analysis. ResultsFor peripheral vs. central BP (mmHg) average levels were 126.6 vs. 122.1 systolic and 79.4 vs. 79.6 diastolic, and 95.1 vs. 97.9 and 47.2 vs. 42.5 for mean and pulse pressure, respectively. CRAE and CRVE averaged 153 μm and 219 μm. Effect sizes (μm) for CRAE for 1 − SD increase in peripheral vs. central BP were −3.77 vs. −3.52 systolic, −3.16 vs. −3.13 diastolic, −3.84 vs. −3.64 for mean BP, and −2.07 vs. −1.83 for pulse pressure (p ≤ 0.006). Models that included two BP components demonstrated that CRAE decreased (p ≤ 0.035) with systolic (peripheral vs. central, −2.87 vs. −2.40) and diastolic (−1.58 vs. −1.80) BP. CRAE decreased with mean BP (−3.53 vs. −3.53; p < 0.0001), but not with pulse pressure (p ≥ 0.19). CRVE was not related to any peripheral or central BP component (p ≥ 0.062). All CRAE regression slopes on corresponding peripheral and central BP components were similar (p ≥ 0.28). ConclusionHigher systolic, diastolic and mean BPs were associated with smaller CRAE, regardless of whether BP was measured centrally or peripherally. Central BP does not refine the inverse association of CRAE and CRVE with peripheral BP.