RESUMO
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.
RESUMO
A comparative study of changes in the contribution of endothelium-dependent hyperpolarization (EDH) induced by activation of the intermediate-conductance calcium-activated potassium channels (IKÑа) channels and the contribution of NO in pial arterial vessels dilation to acetylcholine (ACh) in normotensive (WKY) and spontaneously hypertensive (SHR) rats at the age of 4 and 18 months was conducted. It was found that in WKY, the EDH is mainly expressed in the group of small pial arterial vessels. During aging, the contribution of EDH to the dilatation of small (diameter less than 20 microns) and medium (20-40 microns) vessels decreases, while it increases in arteries with a diameter of more than 40 microns. Hypertension (HT) leads to an increase in the contribution of EDH processes to dilation of vessels of small and medium diameters. Aging, accompanied by long-term HT, reduces the contribution of EDH to dilation. In 18-month-old SHR, this mechanism is expressed only in a group of small vessels. Age-dependent changes in the EDH contribution in pial arterial vessels dilation in WKY and SHR rats are based on the NO synthesis system damage and a change in the NO-mediated contribution in endothelium-dependent vasodilation.
Assuntos
Hipertensão , Artérias Mesentéricas , Animais , Pressão Sanguínea , Endotélio Vascular , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , VasodilataçãoRESUMO
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.
Assuntos
Artérias Cerebrais/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Traumatismo por Reperfusão/fisiopatologia , Vasodilatação/efeitos dos fármacos , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Vasodilatação/fisiologiaRESUMO
Experiments on Wistar rats showed that blood flow in the cortex and subcortical brain structures was not completely restored within 21 days after transient ischemia caused by bilateral carotid artery occlusion with controlled hypotension. After 7 days of reinfusion, the end-diastolic blood flow velocity increases with simultaneous decrease in pulsation index, which indicates the decrease in peripheral vascular resistance. During the following 14 days, peripheral blood resistance increases, as was seen from the increased peak systolic blood flow velocity, mean blood flow velocity over the heart cycle, and pulsation index. These changes are likely a delayed manifestation of ischemic reperfusion injury to brain microvessels (no-reflow phenomenon) and are determined by changes in blood rheologiy and pial vessel lumen.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Isquemia Encefálica/fisiopatologia , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Circulação Cerebrovascular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Animais , Artérias Carótidas/cirurgia , Hipotensão , Ratos , Ratos Wistar , Resistência VascularRESUMO
Reactivity of pial vessels in response to a brain surface irrigation by norepinephrine solution in rats, subjected to transient global cerebral ischemia (2VO+hypo model), was investigated. Four different groups of rats at 2, 7, 14 or 21 days after ischemia were subjected to microvascular studies using in vivo video microscopy method. The diameter changes of pial arteries and veins in response to norepinephrine were measured. It was established that cerebral ischemia led to increase the number of the constrictions to norepinephrine mainly at the vessels to relating to a group of small pial arteries and arterioles and pial veins of the 3rd generation. Reactivity changes were observed in all time points studied. These 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.
Assuntos
Isquemia Encefálica/fisiopatologia , Artérias Cerebrais/fisiopatologia , Veias Cerebrais/fisiopatologia , Circulação Cerebrovascular , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Artérias Cerebrais/metabolismo , Artérias Cerebrais/patologia , Veias Cerebrais/metabolismo , Veias Cerebrais/patologia , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Receptores Adrenérgicos/metabolismoRESUMO
Reactions of pial vessels to hypercapnia were studied in Wistar rats one week after global cerebral ischemia. In ischemic rats, the responsiveness of pial vessels to hypercapnia was diminished, which promoted a decrease in cerebral perfusion reserve. Changes in vascular responsiveness in the arterial and venous subdivisions of the vascular bed were observed and probably resulted from ischemia-provoked down-regulation of the vascular tone.
Assuntos
Isquemia Encefálica/fisiopatologia , Hipercapnia/fisiopatologia , Pia-Máter/irrigação sanguínea , Acetazolamida/toxicidade , Animais , Artérias/fisiopatologia , Circulação Cerebrovascular , Convalescença , Hipercapnia/induzido quimicamente , Ratos , Ratos Wistar , Resistência Vascular , Vasodilatação , Veias/fisiopatologiaRESUMO
The responses of rat pial vessels to red laser irradiation can be mediated by NO. NO mainly affects major arteries and did not contribute to reactivity of small pial arteries and precortical arterioles.
Assuntos
Artérias/efeitos da radiação , Lasers , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Pia-Máter/metabolismo , Pia-Máter/efeitos da radiação , Animais , Artérias/metabolismo , Arteríolas/metabolismo , Arteríolas/efeitos da radiação , Inibidores Enzimáticos/administração & dosagem , Injeções Intravenosas , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/antagonistas & inibidores , Pia-Máter/irrigação sanguínea , RatosRESUMO
Segment-specific characteristics of the reactions of pial arteries of different generations to intravenous injection of norepinephrine were studied under conditions of instrumental stabilization of systemic blood pressure in rats with blocked α- and ß-adrenoceptors.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Artérias Cerebrais/efeitos dos fármacos , Norepinefrina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Pressão Sanguínea , Artérias Cerebrais/metabolismo , Artérias Cerebrais/fisiologia , Microscopia de Vídeo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Experiments on WKY and SHR rats showed that low-intensity laser irradiation reduced the tone of pial arterial vessels thereby potentiating the subsequent constrictor effect of norepinephrine. Irradiation in the red region of the spectrum produced a more pronounced effect in the blue region. The observed effects were less pronounced in SHR rats compared to normotensive WKY rats.
Assuntos
Artérias Meníngeas , Norepinefrina/administração & dosagem , Pia-Máter/irrigação sanguínea , Vasoconstritores/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/fisiopatologia , Infusões Intraventriculares , Terapia com Luz de Baixa Intensidade , Artérias Meníngeas/efeitos dos fármacos , Artérias Meníngeas/efeitos da radiação , Pia-Máter/efeitos dos fármacos , Pia-Máter/efeitos da radiação , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/efeitos da radiação , Vasodilatação/efeitos dos fármacos , Vasodilatação/efeitos da radiaçãoRESUMO
Laser radiation of different power had various effects on the properties of erythrocytes. An increase in the radiation power from 2.2 to 25 mW/cm2 was accompanied by a decrease in the erythrocyte sedimentation rate and an increase in erythrocyte filtration index. Radiation of 50 mW/cm2 induced abnormal erythrocyte aggregation. Increasing the time of irradiation at power intensity of 2.2 mW/cm2 did not potentiate its effect on the blood.
Assuntos
Sedimentação Sanguínea/efeitos da radiação , Agregação Eritrocítica/efeitos da radiação , Deformação Eritrocítica/efeitos da radiação , Eritrócitos/efeitos da radiação , Lasers , Animais , Relação Dose-Resposta à Radiação , Ratos , Ratos WistarRESUMO
Differential characteristic of the reaction of pial arteries of various generations to intravenous administration of norepinephrine was obtained in experiments on rats under artificially stabilized systemic blood pressure.