Effect of mexidol on combined vascular pathology of brain and heart

The effect of mexidol on cerebral blood flow under conditions of experimental myocardial infarction and combined disturbances of cerebral and coronary perfusion in comparison with intact and false-operated rats and rats after global transient ischemia of brain was studied. It is established that mexidol (200 mg/kg) more prominently enhances the blood flow in the parietal region of brain cortex of rats with combined ischemia of brain and heart as compared to intact rats and rats after experimental myocardial infarction. Under conditions of combined pathology, mexidol produces the same cerebrovascular effect as that in animals with cerebral ischemia.     

Cerebrovascular and antiserotoninergic activity of the combination of tropoxin and mexidol

The results of experiments on narcotized rats showed that tropoxin substantially reduces the constrictor reactions of cerebral blood vessels to meta-chlorophenylpiperazine, while not increasing the blood flow in the carotid system of either intact rats or animals with model ischemic damage of brain. In contrast, mexidol increases the cerebral blood flow in rats under conditions of global transient ischemia of brain. A combination of tropoxin and mexidol retains both the anti-serotoninergic activity of tropoxin and the vasodilating effect of mexidol.     

Gabaergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon

The role of GABAergic mechanisms in realization of the effects of afobazole and picamilon on the cerebral circulation was studied in rats. It is found that the cerebrovascular effect of afobazole significantly decreases on the background of the GABA receptor antagonists bicuculline and picrotoxin. This is evidence of an important role of the GABA system in the its cerebrovascular and neuroprotective activity of afobazole. The results of experiments with picamilon showed that the cerebrovascular effect of this drug is not affected by receptor blocking with bicucullin. However, the blocking of chloride channels of the GABA receptors by picrotoxin significantly decreased the effect of picamilon on the cerebral blood flow.     

Effect of typical and atypical anxiolytics on the behavior and electrophysiological parameters of rats with model cerebrovascular pathology

The influence a series of anxiolytics (tranquilizers) on behavioral disturbances was studied in outbread white male rats with cerebrovascular pathology modeled by ligation of common carotid arteries. All studied anxiolytics (diazepam, buspirone, mexidol) exhibited more of less pronounced protective action with respect to the pathology studied. The most significant protective effect was produced by the atypical anxiolytic mexidol. Special features of the effect of mexidol are probably explained by combination of several effects (anxiolytic, nootrope, antioxidant, and antihypoxant). in the pharmacological activity spectrum of this drug.     

Effect of a drug composition containing pyroglutamic acid and pyrrolidone on the cerebral circulation

A drug composition containing pyroglutamic acid and pyrrolidone produces a significant effect on the cerebral circulation in rats and cats, which is manifested by increased cerebral blood flow and by a dose-independent improvement of the microcirculation. The cerebrovascular effects were similarly pronounced in both rats and cats which indicates that the drug action is independent of the animal species. The drug combination studied did not exhibit antiserotonin activity. The data obtained show evidence of a substantial contribution of the cerebrovascular component to the neuroprotector action of the drug composition studied.     

The effect of esafosfina on cerebral circulation in intact and ischemized rat brain

The physiological metabolite esafosfina (fructose 1,6-diphosphate) influences the cerebral circulation of intact male rats. Injected intravenously in a dose of 250 mg/kg, esafosfina improved both the blood supply to brain and the local blood flow in the parietal region. Under the conditions of global transient cerebral ischemia, the cerebrovascular effect of the drug tends to increase. Esafosfina produced dissimilar changes in the arterial blood level, which could be explained by various basic status of the test animals. The pronounced cerebrovascular activity of esafosfina plays a key role in its neuroprotector effect.     

Adamantane derivate enhances cerebral blood flow under conditions of ischemic brain damage

Experiments have shown that adamantane derivate - 5-hydroxyadamantan-2-on (100 mg/kg, i.v.) enhances the local blood flow in the cerebral cortex of rats under global transient brain ischemia conditions, while not influencing the brain blood flow in intact rats. In the same dose, adamantane derivate significantly decreases mortality in rats under conditions of hypergravity ischemia. The cerebrovascular effect of adamantane derivate is abolished by bicuculline (GABA-A receptor blocker), which is evidence for a GABAergic component in the mechanism of the cerebrovascular action ofadamantane derivate.     

激光散斑成像技术测定阿魏酸对大鼠脑血流量的影响

目的：考察阿魏酸对大鼠脑血流量的影响。方法：通过激光散斑成像技术观察腹腔注射阿魏酸后对正常大鼠脑血流量的影响，并对大鼠脑动脉血流和微循环区域血流进行计算分析。结果：正常大鼠腹腔注射阿魏酸50mg·kg-1后，大鼠的脑血管（包括大小动脉和静脉）的形态无明显变化；给药50min后，大鼠脑动脉的血流量缓慢增加，最高可增加到原血流量的170%，并能维持在一个相对较高的水平1h以上；给药60min后，微循环区的血流量渐渐增加，最高可增加到原血流量的150%～160%。结论：阿魏酸能显著增加大鼠大脑动脉及微循环区的血流量，不同区域的血流增加量有所不同。其机制可能与其松弛毛细血管前后括约肌，减少血流阻力及增加心肌收缩力，增加供血量等作用有关。     

Impaired beta-adrenergic mediated cerebral blood flow response in streptozotocin diabetic rats

The influence of intracarotic infusion of isoproterenol on cerebral blood flow, on cerebrovascular CO2-reactivity, and on cerebral glucose metabolism were investigated in streptozotocin diabetic rats. Resting cerebral blood flow in diabetic rats decreased by 26% from a control value of 90 ml/100 g.min. to 66 ml/100 g.min. Intracarotid isoproterenol infusion leads to a significant increase in cerebral blood flow in both groups. The increase in cerebral blood flow in control rats (70%), significantly exceeded that in the streptozotocin diabetic rats (33%). Cerebrovascular reactivity to carbon dioxide was preserved after isoproterenol infusion in both groups and there was no significant difference in the relative cerebral blood flow increase in the two groups. Cerebral glucose metabolism was also unaffected by the isoproterenol infusion. The results indicate that impaired beta-adrenergic mechanisms may play a role for alterations in cerebral blood flow that is seen in diabetes mellitus.     

Impaired β-Adrenergic Mediated Cerebral Blood Flow Response in Streptozotocin Diabetic Rats

Abstract: The influence of intracarotic infusion of isoproterenol on cerebral blood flow, on cerebrovascular CO₂-reactivity, and on cerebral glucose metabolism were investigated in streptozotocin diabetic rats. Resting cerebral blood flow in diabetic rats decreased by 26% from a control value of 90 ml/100 g·min. to 66 ml/100 g·min. Intracarotid isoproterenol infusion leads to a significant increase in cerebral blood flow in both groups. The increase in cerebral blood flow in control rats (70%), significantly exceeded that in the streptozotocin diabetic rats (33%). Cerebrovascular reactivity to carbon dioxide was preserved after isoproterenol infusion in both groups and there was no significant difference in the relative cerebral blood flow increase in the two groups. Cerebral glucose metabolism was also unaffected by the isoproterenol infusion. The results indicate that impaired β-adrenergic mechanisms may play a role for alterations in cerebral blood flow that is seen in diabetes mellitus.     

GABAergic mechanism of the cerebrovascular effect of melatonin

In most experiments on rats under conditions of cerebral global transient ischemia, melatonin substantially enhanced local blood flow and decreased arterial blood pressure. In intact rats, the effect of melatonin on brain perfusion was much less pronounced and the arterial pressure was not influenced at all. The mechanism of melatonin action has been studied with the aid of bicuculline. It is established that the cerebrovascular activity of the epiphyseal hormone is mediated by GABA-A receptors of cerebral vessels. Melatonin (in doses of 1.0 and 5.0 mg/kg) significantly increased survival of rats under conditions of hypergravity ischemia.     

The anti-ischemic effects of 3-hydroxypyridine derivatives in cerebrovascular pathology

The effect of the antioxidant mexidol and two new derivatives of 3-oxypyridine, namely LBK-10 and LBK-39 on the circulation of blood and metabolism of the brain in the postischemic period was studied in acute experiments on narcotized cats under conditions of autohemoperfusion of the cerebral vessels with a stable volume of blood. Therapeutic injection of mexidol and LBK in a dose of 20 mg/kg inhibited the development of the no-flow phenomenon and restored the ischemia damaged metabolism in the brain tissues. LBK-10 reduced the lactate content in the blood flowing from the brain and contributed to constriction of the cerebral vessels.     

Correlations of pharmacokinetics and pharmacodynamics of a combined preparation containing pyrrolidone and pyroglutamic acid

Experiments showed that a new drug composition containing pyrrolidone and pyroglutamic acid exhibits a significant cerebrovascular effect upon peroral administration in rats. The pharmacokinetics of pyrrolidone monitored upon its combined administration with pyroglutamic acid shows that this drug, as a component of the composition, is characterized by a high absolute bioavailability and permeability trough the blood-brain barrier. The presence of pyroglutamic acid slows down the absorption and elimination of pyrrolidone and enhances its distribution in the organs and tissues. There is a correlation between the concentration of pyrrolidone in the brain, on the one hand, and the levels of cerebral microcirculation and arterial pressure on the other hand. An increase in the concentration of pyrrolidone in the brain is accompanied by more intensive cerebral blood flow and by a decrease in the arterial pressure.     

Cerebrovascular effects of a xanthine derivative propentofylline (HWA 285)

The novel xanthine derivative propentofylline, 1-(5′-oxohexyl)-3-methyl-7-propylxanthine (HWA 285), was tested for its effects on cerebral blood flow and cerebrovascular resistance in the anaesthetised baboon. The intravenous administration of propentofylline (0.5 mg/kg/min) led to a small but significant increase in cerebral blood flow. In a separate group of baboons, propentofylline (0.1 mg/kg/min) was administered into the internal carotid artery to avoid interference by the peripheral actions of the drug. This produced a marked increase in cerebral blood flow combined with a fall in cerebrovascular resistance which oulasted the administration of the drug. Propentofylline did not produce any marked change in electroencephalographic (EEG) activity. Finally, the presence of the blood-brain barrier did not appear important to these effects since disruption by hyperosmotic urea did not change the response of cerebral blood flow or cerebrovascular resistance to propentofylline administration. These data suggest that propentofylline produces an increase in cerebral blood flow mainly by dilatation of the cerebrovasculature.     

The action of fenigidin (nifedipine) on central hemodynamics and cerebral blood flow in hypertension

Nifedipine is an effective agent in hypertensive emergencies as well as in the long-term management of hypertension especially for the patients with an increased risk of cerebral hypoperfusion. Nifedipine exerts its blood lowering effect by reducing total peripheral resistance including cerebrovascular resistance. Despite the marked reduction of perfusion pressure, the cerebral blood flow is maintained by nifedipine.     

Effects of nicergoline in experimental models related to pathogenesis of migraine

The effect of nicergoline on cerebral blood flow (CBF), cerebrovascular resistance, the constriction of cerebral vessels caused reflectorily or by 5-hydroxytryptamine (5-HT) and on the transport of 5-HT in rat brain synaptosomes was studied using different experimental models. Nicergoline reduced cerebrovascular resistance in the carotid and vertebrobasilar system. The drug decreased carotid blood flow and local cortical CBF, preceded in some experiments by short-lasting CBF increase. Nicergoline almost completely inhibited brain vessels responses in the carotid and vertebrobasilar systems after tibial nerve stimulation. Simultaneously, inhibition of reflectory discharges of the sympathetic nerves was observed. Nicergoline showed an antiserotonin action by antagonizing the 5-HT effect on the cerebral circulation and inhibiting 5-HT-induced constriction of isolated rabbit basilar artery. The inhibition of uptake and enhancement of the release of 5-HT from brain synaptosomes indicates its ability to affect neuronal transmission in serotoninergic neurons. The effects of nicergoline are probably involved in the realization of its antimigraine action.     

Cerebrovascular and renal actions of bilobil and its effect on the metal ligand homeostasis (clinico-experimental study

The tests on rats with common carotid artery occlusion showed that bilobil increases the cerebral blood flow and decreases brain edema, thus decreasing the loss of experimental animals. The drug also increases the blood circulation and improves the excretory function of kidneys. Under clinical conditions, bilobil increases the cerebral blood flow, normalizes the metal ligand homeostasis, and improves the antioxidant status in children with early forms of cerebrovascular disease (neurocirculate distonia) and attention deficit hyperactivity syndrome.     

P1-purinoceptors in the cerebrovascular bed of the goat in vivo

The possible existence and function of specific P1-purinoceptors in the cerebrovascular bed of the unanesthetized goat have been investigated. Blood flow to one cerebral hemisphere (cerebral blood flow) was measured by means of an electromagnetic flow probe previously implanted around the ipsilateral internal maxillary artery. The injection of adenosine, AMP, ADP and ATP (3-30 micrograms) directly into the internal maxillary artery increased cerebral blood flow and decreased cerebrovascular resistance in a dose-dependent manner. Continuous infusion of 8-phenyltheophylline (8-PT), 100 micrograms/min, into the internal maxillary artery did not alter the resting cerebral blood flow or the cerebrovascular resistance, but significantly inhibited the cerebral vasodilation induced by adenosine, AMP, ADP and, to a lesser degree, ATP. The acetylcholine- and histamine-induced cerebral vasodilation was unaffected by 8-PT. These results indicate that adenosine, AMP, ADP and, at least in part, ATP increase cerebral blood flow by acting on specific P1-purinoceptors located in the cerebrovascular wall. These P1-purinoceptors do not appear to be tonically activated under physiological conditions.     

Cerebral blood flow in patients with chronic cerebrovascular disease: effect of acetyl L-carnitine

The effect of acetyl-L-carnitine on cerebral blood flow was evaluated in ten patients with cerebrovascular disease, who suffered an ischaemic stroke at least six months before the study. All patients performed a computerized tomograph scan and were investigated by Xenon 133 using a brain dedicated Single Photon Emission Computerized Tomography. Acetyl-L-carnitine was administered intravenously (i.v.) at a dosage of 1.5 g. Cerebral blood flow (ml/min. 100 g) was evaluated before and 45 min after the injection. Cerebral blood flow improved in both the ispilateral and controlateral hemisphere of the ischaemic area, but not in the stroke corresponding zone. It is concluded that acetyl-L-carnitine at a dosage of 1.5 g i.v. improves cerebral blood flow in patients with cerebrovascular disease.     

Altered expression of endothelin and its receptors in the brain of SHR-SP at malignant hypertensive stage

Spontaneously hypertensive stroke-prone rats (SHR-SP) suffer spontaneous stroke in part as a result of abnormal cerebrovascular development. Reduction of regional cerebral blood flow in this model has already been demonstrated. This model has three distinct stages of hypertension: pre-hypertensive, typical hypertensive and malignant hypertensive. We investigated the level of endothelin-1 and its receptor expression in the frontal cortex of SHR-SP at the malignant hypertensive stage (35-40 weeks of age), during which time the rats suffer strokes. The cerebral endothelin-1 level, as determined by enzyme-linked immunosorbent assay, was highly increased at this severely hypertensive stage compared to their genetic control, normotensive Wistar-Kyoto rats. This upregulation was associated with an increased expression of endothelin-A receptor, however, another endothelin-1 receptor, endothelin-B, was downregulated. The regional cerebral blood flow in the frontal cortex was reduced by 60% in 40-week-old malignantly SHR-SP as compared to age-matched Wistar-Kyoto rats. Thus, cerebral endothelin-1 expression increased in malignant hypertension in SHR-SP. The enhanced endothelin-1 may activate the endothelin-A receptor, which would, in turn, result in reduced cerebral blood flow. Downregulation of the endothelin-B receptor may cause suppression of endothelium-derived relaxing factors in the brain of SHR-SP and be an underlying factor in their stroke susceptibility.