Pathomorphological manifestations of vascular remodeling in the perifocal areas of ischemic cerebral infarction

Acute disorders of cerebral circulation remain one of the leading causes of death of patients throughout the world. Tissue recovery after a stroke is directly related to active revascularization, which is intensified in the peri-infarction area. Newly formed vessels contribute to the restoration of cellular metabolism in surviving neurons. The processes of vascular remodeling after stroke have been at the center of many clinical and morphological studies in recent years. The aim of the study. To study the processes of vascular remodeling and neoplasm of vessels in the perifocal areas of ischemic cerebral infarctions. Material and methods. The study researched the brain of 29 deceased patients with hemispheric infarctions with different periods of the disease: up to 3 days (n = 5), 6 days (n = 5), 9-12 (n = 10), 30 (n = 5), 45 days (n = 4). The object of the study was perifocal areas of cerebral infarction, as well as areas outside ischemic lesions. The studies were carried out using histological, morphometric and statistical techniques. Results. Studies have shown that in the perifocal areas of cerebral infarction within 3 days from the onset of the disease, the morpho-functional state of the microvasculature was characterized by circulatory and hemocoagulation disorders. Along with destructive changes in blood vessels, processes are directed to improve blood circulation in ischemic areas of the brain. Collateral blood flow increases, dilation of pial vessels is noted with a decrease in the Kernogan index. On the 6th day, the processes of angiogenesis and vasculogenesis are activated, which intensify in the subsequent stages of the disease. In the long term, the efficiency of collateral blood flow in the pial vessels decreases, reduction in the capillary network, and the lumen of large arteries is recalibrated. Conclusions. In the early stages of cerebral stroke (up to 3 days), increased blood circulation in the ischemic areas of the brain occurs due to increased collateral blood flow. From the 6th day, the processes of angiogenesis in the form of capillary budding and the processes of vasculogenesis intensify. In large arterioles, recalibration processes take place. After 30-45 days in the perifocal areas of cerebral infarction, a significant reduction of the capillary network is recorded, which is regarded as a reaction to a decrease in blood supply to the areas of organized infarction.

Study on in Vivo Pial Vessels Alterations and Activity of Isolated Vascular Smooth Muscles in Abdominal Hypertension Rats

Background: Intra-abdominal hypertension is known as a factor affecting cerebral haemodynamics. Sustainably elevated abdominal pressure may disturb the balance of intracranial/blood pressure ratio, eventually developing perfusion pressure to drop. Aim: The aim of this study is to investigate the influence of artificially elevated intra-abdominal pressure upon brain pial vessels condition and contractile reactivity of isolated rat arteria carotis communis and vena jugularis to norepinephrine and serotonin. Materials and methods: The abdominal pressure of rats anaesthetized with xylazine 10 mg/kg and ketamine 100 mg/kg was increased up to 25 mm Hg by insufflation of air through venflon cannula and maintained for period of 1 to 3 hours. Craniotomy of left parietal area was carried out by micro drill. Open scull and cranial window techniques were applied. Outer diameters of superficial pial vessels were measured by USB digital microcamera (magnification up to 400x). Contractile reactivity of smooth muscle preparations from arteria carotis communis and vena jugularis of euthanized abdominal-hypertensive (AH) rats was registered isometrically. Results: Increased smooth muscle reactivity of a. carotis communis from AH rats to serotonin (10−8-10−4 mol/l) but not to norepinephrine compared to controls was registered. The changes tended to be higher in long lasting (3 hours) exposure of AH rats. Increase in outer diameter of pial vessels during maintenance of abdominal hypertension in both open scull and cranial window techniques was found. Conclusions: The increased intra-abdominal pressure causes dilatation of small superficial cerebral blood vessels and increases the smooth muscle reactivity of isolated arteria carotis communis to 5-HT.

The coagulation hemostasis dynamics in rats in the post-ischemic time

Introduction. Ischemic injury to the endothelium influences on a coagulation hemostasis, worsening hemodynamics of cerebral microcirculation as a result of rheological occlusion. The long-term post-ischemic blood clotting system changes are not studied well by now.The work purpose – to study a coagulation hemostasis and endothelial prostacyclin – synthetic activity of pial vessels within 21 days after single short-term transient cerebral ischemia in rat.Material and Methods. Ischemia was reproduced by means of 12-minute time occlusion of both carotids with the simultaneous arterial hypotension. Post-ischemic changes were investigated in 4 groups of rats: on the 3rd, 7th, 14th and 21st day after ischemia. The state of blood clotting system was estimated on time of clot formation in the blood plasma by an automatic optical method with use of screening tests of definition of prothrombin and thrombin clotting time and concentration of fibrinogen. Endothelial prostacyclin – synthetic activity was estimated by pial vessel reaction to indometacin.Results. On the 3rd day after ischemia the increase in prothrombin time was observed. Level of fibrinogen increased on the 3rd and the 14th days of the post-ischemic time. On the 21st day after ischemia thrombin time decreased. The inverse correlation of pial vessel endothelial prostacyclin – synthetic activity with the fibrinogen level and direct correlation with vessel cross-sectional area of these vessels is established.Conclusions. Short-time global cerebral ischemia causes changes of blood clotting system mechanisms lasting for 21 days of the post-ischemic time. Post-ischemic abnormalities in hemostasis system are connected with changes in endothelial prostacyclin – synthetic activity of cerebral vessels that, along with decreased anti-aggregation ability of vascular system, is also the reason of narrowing of the lumen in pial vessels.

The influence of short-time cerebral ischemia on pial vessels adrenoreactivity in rats

Introduction and purpose. It is known that ischemia influences on endothelial reactions, changes metabolic and myogenic mechanisms of cerebral blood flow regulation. But the role of local neurogenic mechanisms of regulation in change of cerebral vessels reactions after ischemia is finally not found out. The aim of the current study was to examine the pial vessels reactivity in response to a brain surface irrigation by norepinephrine solution in rats, subjected to transient global cerebral ischemia, at 2, 7, 14 and 21 days after ischemia. Materials and methods. Transient global cerebral ischemia was induced in anesthetized Wistar rats by clamping of both common carotid arteries for 12 min with simultaneous controlled hypotension to 45±3 mm Hg, followed by blood reinfusion and recovering from anesthesia. Four different groups of rats were re-anesthetized at 2, 7, 14 or 21 days after ischemia and subjected to microvascular studies using in-vivo video microscopy method. The diameter changes of pial arteries and veins in response to norepinephrine were measured. Results and discussion. It was established that cerebral ischemia led to increase number of the constrictions to norepinephrine mainly at the vessels to relating to group of small pial arteries and arterioles and pial veins of the 3-rd generation. Reactivity changes were observed in all time points studied. This changes probably is connected with caused by ischemia the increase in reactivity and sensitivity of pial vessels adrenoceptors. The greatest changes are noted in 14 days after ischemia. The use of non-selective α-adrenergic antagonist - nicergoline at ischemic and intact rats, led to increase number of the constrictions to norepinephrine. But at ischemic rats decrease was more considerable. And number of dilation reactions to norepinephrine at ischemic rats was also above. It can indicate to increase of adrenoceptors reactivity and sensitivity. Conclusions. Thus, transient global cerebral ischemia cause marked and long lasting (3 weeks) increase in pial vessels reactivity in response to norepinephrine, that is probably connected with increase of adrenoceptors reactivity and sensitivity.

Abstract WMP23: Regional Assessment of Multi-phase CTA and CT Perfusion are Equivalent in Predicting Tissue Fate in Ischemic Stroke

Introduction: The use of CT Perfusion (CTP) in acute ischemic stroke (AIS) to determine patients with large ischemic core is still hampered by slow processing time, among other technical/standardization issues. Multi-phase CTA (mCTA) may be quicker and more practical in this regard. We sought to determine i) the performance of mCTA and CTP to predict regional infarction and ii) which mCTA construct(s) corresponds to which CTP parameter . Methods: mCTA and CTP was performed less than 12hrs from ictus in 77 patients with MCA-M1 occlusions. Regional analysis was performed within M2-M6 ASPECTS-regions. mCTA: regional pial vessels were assessed according to three constructs: i) Delay in maximal pial vessel enhancement compared to contralateral hemisphere; ii) Washout of contrast within pial vessels; iii) Extent of maximal pial vessel enhancement compared to contralateral hemisphere (Figure 1). CTP-CBF, CBV, MTT, IRF-T0, and Tmax values were determined. 24-hour MR-DWI or NCCT was used for final infarction. Results: There was a negligible difference in the predictive accuracy of mCTA and CTP in discriminating infarction (i.e., 84.59% and 83.04%, respectively). mCTA-Extent had the largest discriminatory power, while CTP-Tmax had the largest discriminatory power. Conclusion: Herein we show that mCTA assessments, even within small brain regions can help determine tissue fate when adjusted for recanalization, and is as good as CTP. mCTA may be a more practical modality to obtain similar prognostic information for radiological and clinical outcomes in AIS, informing acute treatment and tertiary centre triaging.

Dysfunction of Mouse Cerebral Arteries during Early Aging

Aging leads to a gradual decline in the fidelity of cerebral blood flow (CBF) responses to neuronal activation, resulting in an increased risk for stroke and dementia. However, it is currently unknown when age-related cerebrovascular dysfunction starts or which vascular components and functions are first affected. The aim of this study was to examine the function of microcirculation throughout aging in mice. Microcirculation was challenged by inhalation of 5% and 10% CO2 or by forepaw stimulation in 6-week, 8-month, and 12-month-old FVB/N mice. The resulting dilation of pial vessels and increase in CBF was measured by intravital fluorescence microscopy and laser Doppler fluxmetry, respectively. Neurovascular coupling and astrocytic endfoot Ca2+ were measured in acute brain slices from 18-month-old mice. We did not reveal any changes in CBF after CO2 reactivity up to an age of 12 months. However, direct visualization of pial vessels by in vivo microscopy showed a significant, age-dependent loss of CO2 reactivity starting at 8 months of age. At the same age neurovascular coupling was also significantly affected. These results suggest that aging does not affect cerebral vessel function simultaneously, but starts in pial microvessels months before global changes in CBF are detectable.