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1.
Acta Naturae ; 15(2): 75-80, 2023.
Article in English | MEDLINE | ID: mdl-37538806

ABSTRACT

Cell therapy with mesenchymal stem cells (MSCs) may be a promising technique for cerebral blood flow restoration after transient ischemia. Before a practical application of the cell material, 7-9 days are required for its cultivation. We studied the efficacy of human MSC (hMSC) transplantation performed 7 days after cerebral ischemia/reperfusion (I/R) to help recover cerebral circulation. The intravital micrograph technique was used to comparatively evaluate the vasculature density in the pia mater and the reactivity of the pial arteries in response to acetylcholine (ACh) in rats after I/R (clamping of both carotid arteries and a simultaneous decrease in and strict maintenance of the mean BP at 45 ± 2 mm Hg for 12 min) and with/without hMSC transplantation. Perfusion (P) in the sensorimotor cortex was assessed using laser dopplerography. After 14 and 21 days, the vasculature density in I/R-affected rats was 1.2- to 1.4-fold and 1.2- to 1.3-fold lower, respectively, than that in the controls. The number of ACh-dilated arteries decreased 1.6- to 1.9-fold and 1.2- to 1.7-fold 14 and 21 days after I/R, respectively. After 21 days, the P level decreased 1.6-fold, on average. Administration of hMSCs on day 7 after I/R resulted in complete recovery of the vasculature density by day 14. ACh-mediated dilatation fully recovered only in arteries of less than 40 µm in diameter within 21 days. After 21 days, the P level was 1.2-fold lower than that in the controls but significantly higher than that in rats after I/R without hMSCs. Delayed administration of MSCs after a transient cerebral ischemic attack affords the time for the procedures required to prepare cell material for transplantation and provides a good therapeutic response in the pial microvasculature.

2.
Bull Exp Biol Med ; 168(5): 597-601, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32249400

ABSTRACT

The study examined the effect of H2S on the tone of cerebral arteries in rats after global cerebral ischemia/reperfusion injury and cooperation between NO and H2S in the control over cerebral circulation during the postischemic period. In control sham-operated and in experimental rats with ischemia/reperfusion injury, the diameter of pial arteries was repeatedly measured in vivo under a light microscope after removal of parietal bone and dura mater in 1 h and in 7 days after the surgery. The study established that H2S is an important signaling molecule in pial arteries, where it is responsible for vasodilation. Interaction of H2S and NO augmented dilation of pial arteries; in these arteries, H2S up-regulated the effect of NO/cGMP/sGC/PKG signaling pathways. Partially, the dilating effect of H2S is realized via activation of ATP-sensitive K+ channels in plasmalemma of smooth muscle cells. In the brain, ischemia/reperfusion injury degrades the ability of pial arteries to dilate via inhibition of NO-mediated signaling pathway.


Subject(s)
Cerebral Arteries/drug effects , Hydrogen Sulfide/pharmacology , Reperfusion Injury/physiopathology , Vasodilation/drug effects , Animals , Brain Ischemia/metabolism , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Cerebral Arteries/physiopathology , Cerebrovascular Circulation/drug effects , Hydrogen Sulfide/metabolism , Male , Nitric Oxide/metabolism , Rats , Rats, Wistar , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Signal Transduction , Vasodilation/physiology
3.
Bull Exp Biol Med ; 166(4): 586-590, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30783841

ABSTRACT

Intracerebral transplantation of mesenchymal stem cells to 6- and 12-month-old SHR rats induced angiogenesis in the pia mater. In 6-months-old SHR rats, perfusion in the brain tissue after cell transplantation considerably increased, while in 12-month-old rats it remained practically unchanged. We also observed marked activation of regulatory processes in the cerebral vascular system, most pronounced in 12-month-old rats. Neurogenic and myogenic tone of cerebral vessels increased significantly, while endothelium-dependent tone slightly decreased. The increase in neurogenic and myogenic tone of blood vessels in SHR rats at the age of 6 and 12 months after transplantation of stem cells can be explained by the formation of new smooth muscle cells in the pre-existing arteries walls. Greater muscle mass developed stronger force and contributed to narrowing of the arterial lumen, as a result, there was no increase in blood flow despite the downstream angiogenesis. A slight decrease in endothelium-dependent tone can be explained by increased production of vasodilators by newly formed endothelial cells.


Subject(s)
Cerebrovascular Circulation/physiology , Mesenchymal Stem Cells/cytology , Animals , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Rats , Rats, Inbred SHR , Rats, Inbred WKY
4.
Adv Gerontol ; 30(4): 534-537, 2017.
Article in Russian | MEDLINE | ID: mdl-28968027

ABSTRACT

Using a TV device to study brain microcirculation, we found that after a course of vascular peptide bioregulator the density of microvascular network of pia matter of old hypertensive rats (12 months) sensomotor cortex increased about 1,7 times compared to intact old rates SHR. This perfusion in the tissue of the cerebral cortex and the degree of blood oxygen saturation in the microvasculature of this tissue region raised.


Subject(s)
Cerebral Cortex/blood supply , Cerebrovascular Circulation/drug effects , Hypertension/drug therapy , Microcirculation/drug effects , Pia Mater/blood supply , Animals , Cardiovascular Agents/pharmacology , Cerebrovascular Circulation/physiology , Hypertension/physiopathology , Microcirculation/physiology , Peptides/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY
5.
Bull Exp Biol Med ; 163(1): 129-132, 2017 May.
Article in English | MEDLINE | ID: mdl-28580491

ABSTRACT

Using a TV device for studying microcirculation (×40), we analyzed the density of the whole microvascular network and the density of arterioles in the pia mater of the sensorimotor cortex in SHR rats of different ages (3-4 and 12 months) after intracerebral transplantation of human mesenchymal stem cells. We found that the density of pial microvascular network in SHR rats receiving transplantation of human mesenchymal stem cells increased to a level observed in young Wistar-Kyoto rats.


Subject(s)
Mesenchymal Stem Cell Transplantation/methods , Microvessels/physiology , Animals , Humans , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Microcirculation/physiology , Pia Mater/cytology , Pia Mater/physiology , Rats , Rats, Inbred SHR , Rats, Inbred WKY
6.
Tsitologiia ; 59(4): 279-84, 2017.
Article in English, Russian | MEDLINE | ID: mdl-30188091

ABSTRACT

Elaboration of new methods of correction of microcirculatory disorder in the brain caused by persistent high blood pressure is a topical task both for medicine and for biology. We studied influence of intracerebral transplantation of human mesenchymal stem cells (MSCh) to cerebral microcirculation in young (4 months) and aged (12 months) spontaneously hypertensive rats (SHR). It was shown that transplantation MSCh promoted the rise of the density of microvascular network of young SHR ca. 1.6-fold; density of the arteriolar area of microvascular network of the pia mater increased ca. 1.9-fold. The density of microvascular network of aged SHR increased ca. 1.4­1.5-fold after transplantation MSCh. The perfusion and tissue saturation of sensorimotor cortex of young SHR increased to the level of young normotensive rats, and in aged SHR the perfusion and tissue saturation of sensorimotor cortex was not increased. Conclusion: the intracerebral transplantation MSCh almost completely leveled the pathological changes of the microcirculation in the sensorimotor cortex of the brain of young SHR and improved unimportantly microcirculation in aged SHR.


Subject(s)
Cerebrovascular Circulation , Cerebrovascular Disorders , Hypertension , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/metabolism , Microcirculation , Sensorimotor Cortex , Animals , Cerebrovascular Disorders/metabolism , Cerebrovascular Disorders/pathology , Cerebrovascular Disorders/physiopathology , Cerebrovascular Disorders/therapy , Heterografts , Humans , Hypertension/metabolism , Hypertension/pathology , Hypertension/physiopathology , Hypertension/therapy , Male , Mesenchymal Stem Cells/pathology , Rats , Rats, Inbred SHR , Sensorimotor Cortex/blood supply , Sensorimotor Cortex/metabolism , Sensorimotor Cortex/pathology , Sensorimotor Cortex/physiopathology
7.
Adv Gerontol ; 30(5): 671-675, 2017.
Article in Russian | MEDLINE | ID: mdl-29322732

ABSTRACT

We investigated the influence of vascular peptide bioregulator on microcirculation in the brain cortex of spontaneously hypertensive rats of different ages and figured out whether there is functional cumulation during two-time application of the drug «Slavinorm¼ by above-mentioned animals. It was shown that a single course treatment with vascular peptide bioregulator had increased the density of microvascular network of the pia mater in young animals ca. 1,2-fold and had not affected the perfusion and oxygen saturation of sensorimotor cortex. The second course treatment with «Slavinorm¼ was provided in a 6 months. Functional cumulation was revealed in 12 month-aged rats which had 2 course treatments with vascular peptide bioregulation: the density of microvascular network of the pia mater was increased ca. 1,6-fold; level of perfusion was increased ca. 15% in comparison with intact animals of the same age. These animals were more tolerant to cerebral vasospasm (the application of vasoconstrictor on the surface of the brain): the highest level of tissue oxygen saturation was remained at fairly constant perfusion in comparison with other animals.


Subject(s)
Angiogenic Proteins/pharmacology , Cerebral Cortex/blood supply , Microcirculation/physiology , Microvessels/drug effects , Age Factors , Animals , Rats , Rats, Inbred SHR , Rats, Inbred WKY
8.
Bull Exp Biol Med ; 161(2): 300-3, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27383168

ABSTRACT

Using a TV unit for microcirculation studies, we studied the density of the entire microvascular network and its arterial compartment in the pia mater of the sensorimotor cortex in intact young and aged rats (2-3 and 22-24 months) and aged rats after a course of vascular peptide bioregulator Slavinorm. The experiments showed that the density of microvascular network in intact animals decreased by 1.6 times with aging. Treatment with the peptide bioregulator 2.5-fold increased the density of the microvascular network in aged rats in comparison with intact animals of the same age, the density of the arterial compartment of the microvascular network in the pia mater increased by 2.8 times.


Subject(s)
Angiogenesis Inducing Agents/pharmacology , Microvessels/drug effects , Pia Mater/blood supply , Proteins/pharmacology , Sensorimotor Cortex/blood supply , Aging , Animals , Drug Evaluation, Preclinical , Male , Neovascularization, Physiologic/drug effects , Rats, Inbred WKY
9.
Bull Exp Biol Med ; 160(3): 298-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26742741

ABSTRACT

We studied the density and structure of the microvascular network of the pia mater, the blood flow rate and oxygen saturation in the sensorimotor cortex of young spontaneously hypertensive rats (SHR). The density of the microvascular network in hypertensive animals was by ~1.4 times lower than in normotensive Wistar-Kyoto rats (control) and arteriolar bed density was lower by ~1.9 times. The blood flow rate in tissue and oxygen saturation in the sensorimotor cortex in SHR rats were significantly lower than in control animals.


Subject(s)
Cerebral Cortex/physiology , Hypertension/physiopathology , Microcirculation/physiology , Animals , Male , Rats , Rats, Inbred WKY
10.
Adv Gerontol ; 29(2): 291-296, 2016.
Article in Russian | MEDLINE | ID: mdl-28514548

ABSTRACT

Using a TV device to study brain microcirculation, we found that after a course of vascular peptide bioregulator the density of microvascular network of pia matter of old rats (22-24 months) sensomotor cortex increased about 2,5-2,8 times compared to control old rates; and noradrenaline-induced constriction reactions and acetylcholine-induced dilative reactions of the pial arterioles increased significantly. This perfusion in the tissue of the cerebral cortex is not increased, but the degree of blood oxygen saturation in the microvasculature of this tissue region raised.


Subject(s)
Angiogenic Proteins/pharmacology , Cerebrovascular Circulation , Microcirculation , Pia Mater/blood supply , Sensorimotor Cortex , Animals , Biological Factors/pharmacology , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Drug Monitoring/methods , Microcirculation/drug effects , Microcirculation/physiology , Microvessels/drug effects , Microvessels/physiology , Oxygen Consumption/drug effects , Perfusion Imaging/methods , Protective Agents/pharmacology , Rats , Sensorimotor Cortex/drug effects , Sensorimotor Cortex/metabolism , Treatment Outcome
11.
Adv Gerontol ; 29(4): 567-572, 2016.
Article in English, Russian | MEDLINE | ID: mdl-28539013

ABSTRACT

We studied the density of the microvascular network in the pia mater, the tissue perfusion and saturation of the oxygen of sensorimotor cortex of hypertensive rats of different ages. Our investigations shown that the microvascular density in the pia mater was not only decreased, but also was increased. The perfusion of sensorimotor cortex was reduced and tissue saturation was enlarged. By the age of 12 months orienting-exploratory rats behavior became worse significantly in all major indicators of the test «open field¼.


Subject(s)
Aging , Hypertension , Microcirculation , Pia Mater/blood supply , Sensorimotor Cortex , Age Factors , Aging/physiology , Aging/psychology , Animals , Behavior, Animal/physiology , Hypertension/pathology , Hypertension/physiopathology , Microvessels/diagnostic imaging , Microvessels/pathology , Perfusion Imaging/methods , Rats , Sensorimotor Cortex/pathology , Sensorimotor Cortex/physiopathology
12.
Adv Gerontol ; 28(1): 48-52, 2015.
Article in Russian | MEDLINE | ID: mdl-26390610

ABSTRACT

Using a TV device to study microcirculation in brain we found that intracerebral transplantation of mesenchymal stem cells to 12-months old rats led to a significant increase (circa 1,5-fold times) of microvascular density in pia tissue and to increased constriction reactions of pia arterioles in response to noradrenalin application on a brain surface. Both microvascular density and pia arterioles reactivity was completely preserved in aging until 22-24 months.


Subject(s)
Aging/physiology , Cerebral Cortex/blood supply , Microcirculation/physiology , Microvessels/cytology , Animals , Male , Mesenchymal Stem Cell Transplantation , Neovascularization, Physiologic , Pia Mater/blood supply , Rats , Rats, Inbred WKY
13.
Adv Gerontol ; 28(3): 466-471, 2015.
Article in Russian | MEDLINE | ID: mdl-28509482

ABSTRACT

Male Wistar-Kyoto rats, aged 22-24 months, were intracerebrally transplanted syngeneic mesenchymal stem cells (MSC). Cognitive functions of these animals were tested in 3 weeks. The density of microvascular bed, the tissue blood flow, saturation of mixed blood in cortex microvessels were measured under the standard conditions, under the impact of noradrenaline and in the context of global ischemia. The control groups consisted of rats aged 2-3 months and 22-24 months. MSC transplantation have a positive impact on the microcirculation in brain cortex of old animals: reduction of vascular density was prevented, level of saturation in the blood vessels was increased, which enabled animals to endure easier extreme impacts, but did not correct age-related deterioration of cognitive functions.


Subject(s)
Aging , Brain Ischemia , Mesenchymal Stem Cell Transplantation/methods , Microvessels/physiopathology , Norepinephrine/pharmacology , Aging/physiology , Aging/psychology , Animals , Behavior, Animal/physiology , Brain Ischemia/blood , Brain Ischemia/physiopathology , Brain Ischemia/prevention & control , Cerebral Cortex/blood supply , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Male , Microcirculation/drug effects , Microcirculation/physiology , Rats , Rats, Inbred WKY , Treatment Outcome , Vasoconstrictor Agents/pharmacology
14.
Tsitologiia ; 56(4): 273-82, 2014.
Article in Russian | MEDLINE | ID: mdl-25509161

ABSTRACT

Using a television-based vital microscopy method and immunohystochemical analysis, we have assessed the effect of intracerebral transplantation of syngeneic mesenchymal stem cells (MSC) on the brain cortex structure and the microcirculation in the pia mater of old rats. Using "open field" system, we have studied the effect of MSC transplantation on position-finding and discovery behavior of older animals. We have found that density of microvascular network of the pia mater increased ca. 1.9-fold in MSC recipients, compared to age-matched intact animals. Density of the arteriolar area of microvascular network of the pia mater increased ca. 2-fold. Reactivity of the newly formed arterioles was nearly equal to that of native microvessels. Intracerebral transplantation procedure itself was traumatic for brain cortex of rats, but it had no effect on the microcirculation in the contralateral hemisphere. Intracerebral transplantation of MSC did not improve locomotor behavi- or and emotional stage of old rats, did not increase their position-finding and discovery activity.


Subject(s)
Aging , Cerebral Cortex/blood supply , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Animals , Behavior, Animal , Cerebral Cortex/pathology , Exploratory Behavior/physiology , Injections, Intraventricular , Male , Mesenchymal Stem Cells/cytology , Microscopy, Video , Motor Activity/physiology , Neovascularization, Physiologic , Pia Mater , Rats , Rats, Wistar , Transplantation, Isogeneic
15.
Bull Exp Biol Med ; 157(5): 663-5, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25257436

ABSTRACT

Using a TV device for studying microcirculation (×160), we analyzed the responses of arterioles in the pia mater of the sensorimotor cortex in young (2-3 months) and old (22-24 months) rats after local application of a vasoconstrictor (norepinephrine, 10(-6) M) or vasodilator (acetylcholine, 10(-6) M). The responses of the arterioles were evaluated by changes in their diameter and by the number of responding vessels in the field of view. The constrictor responses of the pial arteries to norepinephrine did not significantly differ in intact young and old rats. The number and degree of dilatory responses to acetylcholine in old rats were lower than in young animals by 14 and 30%, respectively. Intracerebral transplantation of mesenchymal stem cells to old rats had practically no effect on reactivity of pial arterioles to acetylcholine, while the number of constricted vessels in response to norepinephrine increased by ~20%.


Subject(s)
Arterioles/physiology , Brain/physiology , Mesenchymal Stem Cell Transplantation , Animals , Brain/blood supply , Male , Rats , Rats, Inbred WKY
16.
Adv Gerontol ; 27(3): 447-51, 2014.
Article in Russian | MEDLINE | ID: mdl-25826989

ABSTRACT

Male Wistar-Kyoto rats aged 22-24 months were intracerebrally transplanted with syngenic bone marrow mesenchymal stem cells (BM MSC) established from the donor aged 3-4 months and 20-22 months, respectively. Using a TV device to study microcirculation in vivo, we have established that transplantation of BM MSC from young donors increased a density of the microvascular network in the pia mater of the sensorimotor cortex in old rats approximately 1.9-fold, comparing to age-matched controls, while a density of the arteriolar compartment increased approximately 2.1-fold. Transplantation of BM MSC from old donors did not lead to the significant increase in the density of the microvascular network in the pia mater, while a density of the arteriolar compartment increased approximately 1.5-fold.


Subject(s)
Aging/physiology , Cerebral Cortex/blood supply , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/cytology , Microvessels/cytology , Pia Mater/blood supply , Animals , Cell Differentiation/physiology , Cerebral Cortex/cytology , Male , Mesenchymal Stem Cells/physiology , Neovascularization, Physiologic , Pia Mater/cytology , Rats, Inbred WKY
17.
Bull Exp Biol Med ; 155(1): 134-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23667891

ABSTRACT

We studied the effect of intracerebral transplantation of bone marrow mesenchymal stem cells on microcirculation (density of microvascular network and reactivity of arterioles) in the pia mater of 2-3-month-old rats. It was found that after transplantation of mesenchymal stem cells, the density of pial microcirculatory network in the contralateral hemisphere significantly increased (by 1.7 times; p<0.05) in comparison with both intact animals and controls. The number of arterioles in the studied area increased most markedly (by ≈2.5 times; p<0.05) in comparison with other groups. Intracerebral transplantation of mesenchymal stem cells or conditioned culture medium (α-MEM) had no effect on reactivity of pial arterioles.


Subject(s)
Mesenchymal Stem Cell Transplantation , Microcirculation , Microvessels/cytology , Neovascularization, Physiologic , Pia Mater/blood supply , Animals , Brain/blood supply , Mesenchymal Stem Cells , Rats
18.
Bull Exp Biol Med ; 154(4): 548-52, 2013 Feb.
Article in English, Russian | MEDLINE | ID: mdl-23486601

ABSTRACT

Using a TV device for studying microcirculation (×40), we studied the density of the whole microvascular network and arteriolar its compartment in the pia mater of the sensorimotor cortex in rats of different age (2-3, 12, and 24 months) after intracerebral transplantation of mesenchymal stem cells or nutrient medium (control). The density of the microvascular network in the pia mater remained practically unchanged until 1 year, but then decreased by 1.8 times with adding (up to 2 years). MSC transplantation 1.5-1.8-fold increased the density of the pial microvessels in animals of all age groups in comparison with intact and control rats; the density of the arteriolar compartment increased by 2.1-2.4 times. Intracerebral injection of MSC to 1-year-old animals prevented pathological decrease in the density of microvascular network during the next year of life.


Subject(s)
Mesenchymal Stem Cells/cytology , Microvessels/cytology , Pia Mater/cytology , Animals , Male , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Neovascularization, Physiologic , Rats , Rats, Wistar
19.
Adv Gerontol ; 26(3): 437-41, 2013.
Article in Russian | MEDLINE | ID: mdl-24640690

ABSTRACT

We studied the density of whole microvascular network and separately the density of arterioles in the pia mater of sensorimotor cortex of rats of different ages. Also pial arteriolar reactivity on exposure to norepinephrine or acetylcholine chloride was evaluated. The microvascular density and the arteriolar reactivity in the pia mater were not significantly changed before the age of 12 months. In the age of 22-24 months the density of whole microvascular network decreased 1,7 times at the mean and the density of arterioles decreased 1,2 times. There were no significant changes of pia arterioles constriction during the animals life but dilatation was noticeably worse in senility. Orientation and exploratory behavior got worse to the age of 22-24 months: the number of behavioral acts in the "open field" test decreased 1,5-2,3 times in comparison with young animals.


Subject(s)
Aging/physiology , Cerebrovascular Circulation , Microcirculation/physiology , Motor Cortex/blood supply , Pia Mater/blood supply , Somatosensory Cortex/blood supply , Vasodilation/physiology , Animals , Arterioles/physiology , Male , Rats , Rats, Inbred WKY
20.
Adv Gerontol ; 26(2): 236-241, 2013.
Article in Russian | MEDLINE | ID: mdl-28976146

ABSTRACT

Male Wistar-Kyoto rats (12 and 22-24 months old) were intracerebrally transplantated with syngeneic mesenchymal stem cells (MSC). Three weeks or one year later, orientation and exploratory behavior of the same animals (not 2 years old) was assessed using an «open field¼ test. Older rats (22-24 months old) were inhibited in the basic behavioral acts in comparison to younger animals (2-3 months old). Transplantation of MSC did not cause improvement of an orientation and exploratory behavior of aged rats. Morphological and immunohistochemical analysis suggests intracerebral MSC transplantation led to the injury of the cortex of the ipsilateral hemisphere.

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