I. V. Sergeev

Arteriogenesis in the Pia Matter of the Rat Brain Cortex after Intracerebral Injection of Mesenchymal Stem Cells

We studied the effect of intracerebral transplantation of mesenchymal stem cells on the density of pial arterioles in rat brain cortex. It was shown that intracerebral transplantation although causes damage to about half the area of the ipsilateral pia mater, does not change the density of the microvascular network neither in border region of the injured tissue, nor in the contralateral hemisphere. Intracerebral transplantation of mesenchymal stem cells promoted arteriogenesis in the pia mater of the contralateral hemisphere: density of arterioles in this area was signifi cantly (by about 2.5 times higher) than in other experimental animals.

The efficiency of mesenchymal cell intracerebral transplantation for corrections of cerebral microcirculation age-related alterations in rats

Using television-based vital microscopy and immunohistochemical analysis, we have assessed the effect of syngeneic mesenchymal stem-cell (MSC) intracerebral transplantation on the brain cortex structure and microcirculation in the pia mater of old rats. Setting up the “open field” system, we studied the effect of MSC transplantation on the position-finding and discovery behavior of old animals. We found that the density of microvascular network of the pia mater increased by about 1.9-fold in MSC recipients compared to age-matched controls. The density of the arteriolar area of microvascular network of the pia mater approximately doubled. The reactivity of newly developed arterioles was nearly equal to that of native microvessels. The intracerebral transplantation procedure was itself traumatic for rat brain cortex, but it did not affect microcirculation in the contralateral hemisphere. Intracerebral transplantation of MSCs did not improve the locomotor behavior and emotional stage of old rats; neither did it increase their position-finding and discovery activity.

Effect of Intracerebral Transplantation of Mesenchymal Stem Cells on Pial Microcirculation in Rats

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.

Aging-related changes in the blood flow rate and oxygen saturation of the blood in the cerebral cortex of rats

Male Wistar-Kyoto rats received intracerebral transplantation of syngeneic mesenchymal stem cells (MSCs) at 22–24 months of age. The cognitive function of these animals was tested and the microvasculature density, tissue blood-flow rate, and oxygen saturation of mixed blood in the cortical microvasculature were measured in the sensorimotor cortex of the contralateral brain hemisphere under standard conditions, after norepinephrine application, and in global ischemia 3 weeks after cell transplantation. Rats at 2–3 and 22–24 months of age were used as the control groups. MSC transplantation had a positive impact on microcirculation in the cerebral cortex of old animals: deterioration of the vascular bed was prevented and the level of oxygen saturation of blood in the microvasculature was elevated; therefore, the tolerance of animals to the spasm of pial arterioles and global cerebral ischemia was increased, although aging-related decline of cognitive functions was not alleviated.

Age-related changes of microcirculation in pial blood vessels of the sensorimotor cortex of the rat brain

We studied the density of the entire microvascular network and arterioles in the pia mater of the sensorimotor cortex in rats of different ages. The responses of pial arterioles to noradrenaline and acetylcholine chloride were also studied. Our results showed that the density of the microvascular network and reactivity of arterioles in the pia mater did not significantly change before the age of 12 months. At the age of 22–24 months, the density of the entire microvascular network was decreased by 1.7 times; the density of arterioles was decreased by 1.2 times. The contractility of pial arterioles did not significantly change during the rat lifespan; however, their ability to dilate became poorer with age. Exploratory behavior was impaired by the age of 22–24 months: the number of events in the open-field test was decreased by 1.5–2.3 times in comparison with young animals.

Effect of Transplantation of Mesenchymal Stem Cells on the Density of Pial Microvascular Network in Rats of Different Age

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.

Effects of Vascular Peptide Bioregulator on the Density of Microvascular Network in the Brain Cortex of Aged Rats

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.

The effect of vascular peptide bioregulator on microcirculation in the brain cortex of old rats

At a video facility for the study of intravital brain microcirculation, we found that, after a course treatment with vascular peptide bioregulator, the microvasculature density of the pial tunic in old (22–24 months) rats increased by about 2.5–2.8 times; the constriction and dilative reactions of the pial arterioles increased after the application of noradrenaline and acetylcholine onto the brain surface, respectively. However, perfusion into brain tissues did not increase, but the degree of oxygen saturation in microvessels of this tissue region increased.

The effect of mesenchymal stem cell donor age on the density of the pia microvascular network in the cerebral cortex of old recipient rats

We transplanted syngenetic bone marrow mesenchymal stem cells (BM MSCs) obtained from 3- to 4-month-old or 20- to 22-month-old donors into the brain of 22- to 24-month-old male Wistar–Kyoto rats. Using a TV device to study microcirculation in vivo, we found that transplantation of BM MSCs from young donors increased the densities of the microvascular network in the pia mater of the sensorimotor cortex and of the arteriolar compartment in old rats approximately by values of 1.9 and 2.1 as compared to agematched controls. Transplantation of BM MSCs from old donors did not significantly influence the density of the microvascular network in the pia mater, while the density of the arteriolar compartment increased by approximately 1.5 times.

The effect of intracerebral transplantation of mesenchymal stem cells on orientation and exploratory behavior of aged animals

Male Wistar-Kyoto rats (12 and 22–24 months old) were intracerebrally transplanted with syngeneic mesenchymal stem cells (MSCs). Then, the orientation and exploratory behavior of these animals at the age of 2 years (i.e., 1 year or 3 weeks after MSC transplantation) was assessed in an “open field” test. The basic behavioral acts of the older rats (22–24 months old) were inhibited compared to the younger animals (2–3 months old). The transplantation of MSCs did not improve the orientation and exploratory behavior of old rats. The results of morphological and immunohistochemical analysis suggest that the intracerebral MSC transplantation led to partial injury of the ipsilateral hemisphere cortex.