Brain blood supply and beta-endorphin and corticotropin content on exposure to thyroliberin

Thyroliberin produces a marked depressant action on the reflex cerebrovascular constriction reactions. The lack of changes in the content of immunoreactive beta-endorphine in blood and CSF indicates that apparently the cerebrovascular effects of the drug are not mediated via the opioid system but are due to a direct influence of thyroliberin on the central mechanisms by which brain circulation is regulated. Thyroliberin increases the blood corticotropin content, which causes an elevation of the arterial blood pressure and cerebrovascular tension. On the contrary, in the CSF the corticotropin level decreases after thyroliberin administration. The data obtained show that there is no correlation between the content of beta-endorphine and corticotropin in blood and CSF under the action of thyroliberin.     

Difference in the cerebrovascular effects of phenoxybenzamine]

The isotope, electromagnetic and resistographic investigation showed phenoxybenzamine to be capable of producing different effects on the blood supply of different regions of the brain. The preparation enhanced the circulation of the vertebro-basilar system and decreased it in the carotic one. Phenoxybenzamine also significantly inhibited the nervous control of the cerebral circulation. It inhibited the reflex reaction of cerebral vessels, changed the cerebral blood flow by stimulation of cervical sympathetic nerves and was capable of protecting against experimental cerebrovascular disorders. These data allow one to recommend phenoxybenzamine in neurological and neurosurgical clinics for the treatment of cerebrovascular disorders in the vertebro-basilar arterial system.     

Influence of sex steroid hormones on cerebrovascular function.

The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens, androgens, and progestins all influence the function and pathophysiology of the cerebral circulation. Estrogen decreases cerebral vascular tone and increases cerebral blood flow by enhancing endothelial-derived nitric oxide and prostacyclin pathways. Testosterone has opposite effects, increasing cerebral artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased by testosterone and progesterone. Evidence suggests that sex steroids also modulate blood-brain barrier permeability. Estrogen has important protective effects on cerebral endothelial cells by increasing mitochondrial efficiency, decreasing free radical production, promoting cell survival, and stimulating angiogenesis. Although much has been learned regarding hormonal effects on brain blood vessels, most studies involve young, healthy animals. It is becoming apparent that hormonal effects may be modified by aging or disease states such as diabetes. Furthermore, effects of testosterone are complicated because this steroid is also converted to estrogen, systemically and possibly within the vessels themselves. Elucidating the impact of sex steroids on the cerebral vasculature is important for understanding male-female differences in stroke and conditions such as menstrual migraine and preeclampsia-related cerebral edema in pregnancy. Cerebrovascular effects of sex steroids also need to be considered in untangling current controversies regarding consequences of hormone replacement therapies and steroid abuse.     

Cerebral infarction--a general-medical problem]

A knowledge of events accompanying the acute coronary failure may help understanding the acute cerebral blood flow insufficiency leading to brain infarction. Cerebral blood flow should be treated as an integral part of the systemic blood circulation. It is of importance when the disease produces lesions to the vascular wall, and the brain looses its autoregulation functions. In such a situation every extracerebral disorders--even slight--may produce extensive lesions to nervous tissue. Therefore, the treatment of the acute cerebral circulation failure requires proper functioning of all factors which may affect hemodynamics and tissue metabolism. Duration of cerebral flow disorders plays an important role in the avoidance of unfavourable complications such as brain infarction. Therefore, every physician is obliged to undertake any possible actions preventing such complications.     

Cardiovascular effects of centrally administered endothelin-1 and its relationship to changes in cerebral blood flow

Intracerebroventricular (i.c.v.) injection of endothelin-1 (ET-1; 100 ng, i.c.v.) produced an initial pressor (24%) (peak at 3 min following ET-1 administration) and a delayed depressor (−40%) (30 and 60 min following ET-1 administration) effects in urethane anesthetized rats. The pressor effect of ET-1 was due to an increase (21%) in cardiac output, while the depressor effect of ET-1 was associated with a marked decrease (−46%) in cardiac output. Stroke volume significantly decreased at 30 and 60 min after the administration of ET-1. No change in total peripheral vascular resistance and heart rate was observed following central administration of ET-1. The effects of ET-1 on blood pressure, cardiac output and stroke volume were not observed in BQ123 (10 μg, i.c.v.) treated rats. Blood flow to the cerebral hemispheres, cerebellum, midbrain and brain stem was not affected at 3 min, but a significant decrease in blood flow to all the regions of the brain was observed at 30 and 60 min following central administration of ET-1. BQ123 pretreatment completely blocked the central ET-1 induced decrease in blood flow to the brain regions. It is concluded that the pressor effect of centrally administered ET-1 is not accompanied by a severe decrease in brain blood flow, however, a subsequent decrease in blood pressure is associated with a decrease in blood flow to the brain. The cardiovascular effects of ET-1 including decrease in brain blood flow are mediated through central ET_A receptors.     

Acute effects of three isoflavone class phytoestrogens and a mycoestrogen on cerebral microcirculation

Phytoestrogens and mycoestrogens are naturally occurring plant and fungus secondary metabolites with estrogen-like structure and/or actions. We aimed to check the hypothesis that phytoestrogens and mycoestrogens, due to their ability to elicit cerebral vasodilation, can induce acute increases in brain blood perfusion. For this purpose, we continuously recorded cerebrocortical perfusion by laser-Doppler flowmetry in anesthetized rats receiving intracarotid infusions (1 mg/kg) of one of the following estrogenic compounds: biochanin A, daidzein, genistein or zearalanone. We have shown the ability of two isoflavone class phytoestrogens (daidzein and biochanin A) and the mycoestrogen zearalanone to induce acute increases in brain blood flow when locally infused into the cerebral circulation of anesthetized rats. The isoflavone genistein failed to induce a significant increase in brain perfusion. No concomitant changes in blood pressure were recorded during the cerebral effects of the estrogenic compounds. Therefore, these microcirculatory effects were due to direct actions of the estrogenic compounds on the cerebrovascular bed.     

A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.     

Effects of aspirin and indomethacin on cerebral circulation in the conscious rat: Evidence for a physiological role of endogenous prostaglandins

The purpose of this work was to evaluate the effects of equipotent doses of two different inhibitors of cyclo-oxygenase, indomethacin and aspirin, on cerebral blood flow and cerebral vascular resistances in the conscious undisturbed rat, using the reference sample radioactive microsphere method. We found that both, aspirin (50 mg/kg) and indomethacin (5 mg/kg) at 3, 15 and 60 min after their intravenous administration, increased cerebral vascular resistances and decreased cerebral blood flow to a similar extent. Both drugs completely abolished the hypotensive effect of 5 mg/kg i.v. arachidonic acid and they did not change arterial PO₂, PCO₂ or pH values. We conclude that the pharmacological inhibition of cyclooxygenase in the conscious undisturbed rat leads to a cerebral vasoconstriction and consequently to a decrease in cerebral blood flow. Our results evidence that prostaglandins are a physiological factor that actively contributes to the maintenance of cerebral circulation.     

Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism

The purpose of the present investigation was to examine the effects of an extract of Ginkgo biloba (EGB) on blood glucose levels, on local cerebral blood flow as well as on cerebral glucose concentration and consumption. The local cerebral blood flow (LCBF) was measured in conscious rats by means of the 14C-iodoantipyrine technique and local cerebral glucose utilization (LCGU) by 14C-2-deoxy-glucose autoradiography. EGB increased the LCBF in 39 analyzed, anatomically defined brain structures by 50 to 100 per cent. No influence of EGB on LCGU was demonstrable. However, EGB enhanced the blood glucose level dose-dependently. Substrates and metabolites of energy metabolism were measured in the cortex of the isolated rat brain perfused at constant rate and with 7 mmol/l glucose added to the perfusion medium. In these experiments EGB decreased the cortical glucose concentration without other substrate levels being changed. These results suggest that glucose uptake may be inhibited by EGB. It is argued that the effects of EGB on brain glucose concentration and blood flow may contribute to its protection of brain tissue against ischemic or hypoxic damage.     

Cerebrovascular Effects of Amyloid-ß Peptides: Mechanisms and Implications for Alzheimer's Dementia

1. The amyloid ß-peptide (Aß) is involved in the mechanisms of Alzheimer dementia. This paper reviews experimental evidence indicating that Aß exerts profound effects on the regulation of the cerebral circulation.2. Thus, Aß compromises the ability of cerebral endothelial cells to produce vascular relaxing factors, impairs the ability of cerebral blood vessels to maintain adequate flow during hypotension, and attenuates the increases in CBF evoked by enhanced brain activity.3. Studies in transgenic mice overexpressing the amyloid precursor protein suggest that these cerebrovascular alterations disrupt the delicate balance between the brain's energy requirements and cerebral blood supply, rendering the brain more vulnerable to ischemic injury.4. The findings support the recently emerged notion that vascular factors play a pathogenic role in the early stages of Alzheimer dementia.     

Abnormal arterial flows by a distributed model of the fetal circulation

Modeling the propagation of blood pressure and flow along the fetoplacental arterial tree may improve interpretation of abnormal flow velocity waveforms in fetuses. The current models, however, either do not include a wide range of gestational ages or do not account for variation in anatomical, vascular, or rheological parameters. We developed a mathematical model of the pulsating fetoumbilical arterial circulation using Womersley's oscillatory flow theory and viscoelastic arterial wall properties. Arterial flow waves are calculated at different arterial locations from which the pulsatility index (PI) can be determined. We varied blood viscosity, placental and brain resistances, placental compliance, heart rate, stiffness of the arterial wall, and length of the umbilical arteries. The PI increases in the umbilical artery and decreases in the cerebral arteries, as a result of increasing placental resistance or decreasing brain resistance. Both changes in resistance decrease the flow through the placenta. An increased arterial stiffness increases the PIs in the entire fetoplacental circulation. Blood viscosity and peripheral bed compliance have limited influence on the flow profiles. Bradycardia and tachycardia increase and decrease the PI in all arteries, respectively. Umbilical arterial length has limited influence on the PI but affects the mean arterial pressure at the placental cord insertion. The model may improve the interpretation of arterial flow pulsations and thus may advance both the understanding of pathophysiological processes and clinical management.     

Long-term course of the cerebral circulatory function after brain irradiation in rats

Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (delta IAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis.     

Role of Nociceptin/Orphanin FQ in the physiologic and pathologic control of the cerebral circulation

Nociceptin/orphanin FQ is a newly described member of the opioid family. Previous minireviews in this series have described the contribution of important factors, including opioids, in the regulation of the cerebral circulation during physiologic and pathologic conditions. The present review extends these initial comments to an opioid whose vascular actions have only very recently been appreciated. In particular, this review discusses the contribution of nociceptin/orphanin FQ to impaired cerebral hemodynamics after cerebral hypoxia/ischemia and traumatic brain injury.     

Neurogenic Neuroprotection

1. Stimulation of the rostral-ventromedial pole of the cerebellar fastigial nucleus exerts powerful effects on systemic and cerebral circulation.2. Excitation of fibers passing through the fastigial nucleus evokes sympathoactivation and increases in arterial pressure.3. Increase in cerebral blood flow evoked by excitation of fibers passing through the FN is mediated by intrinsic brain mechanisms independently of metabolism.4. Excitation of the fastigial nucleus neurons in contrast decreases arterial pressure and cerebral blood flow. The latter probably is secondary to the suppression of brain metabolism.5. Excitation of the fastigial nucleus neurons significantly decreases damaging effects of focal and global ischemia on the brain.6. The fastigial nucleus-evoked neuroprotection can be conditioned: 1-h stimulation protects the brain for up to 3 weeks.7. Other brain structures such as subthalamic cerebrovasodilator area and dorsal periaqueductal gray matter also produce long-lasting brain salvage when stimulated.8. More than one mechanism may account for neurogenic neuroprotection.9. Early neuroprotection, which develops immediately after the stimulation, involves opening of potassium channels.10. Delayed long-lasting neuroprotection may involve changes in genes expression resulting in suppression of inflammatory reaction and apoptotic cascade.11. It is conceivable that intrinsic neuroprotective system exists within the brain, which renders the brain more tolerant to adverse stimuli when activated.12. Knowledge of the mechanisms of neurogenic neuroprotection will allow developing new neuroprotective approaches.     

Effect of microwave radiation on regional blood flow and tissue oxygenation in the brain

The effect of irradiation of the central nervous system by microwaves (MW) at a frequency of 2450 MHz and power 5-40 W on the regulation of cerebral circulation and oxygen supply to the nervous tissue were studied in rabbits. Local irradiation of the exposed cerebral cortex resulted in hyperemia and hyperoxia in the zone of exposure induced by the hyperthermal effect of MW. When the region of the medulla oblongata was irradiated even with low MW power (not leading to hyperthermia), the local circulation and oxygen tension increased in the whole brain, apparently due to the impairment of the regulation of the cerebral blood flow and oxygen supply to the brain tissue.     

Effects of an analogue of thyrotrophin-releasing hormone, RX77368, on infarct size and cerebral blood flow in focal cerebral ischaemia in the rat

Effects of a stable analogue of thyrotrophin-releasing hormone, RX77368, on cerebral blood flow and infarct size have been studied in an acute model of cerebral ischaemia in the rat. Two hours after electrocoagulation of the left middle cerebral artery (MCA), the mean area of ischaemia (+/- SEM), determined histochemically, was 11.5 +/- 2.2% of a single hemisphere and blood flow, determined using radiolabelled microspheres, was reduced by 40% in the left forebrain (p less than 0.001 compared with sham-operated animals). Administration of RX77368 (50 micrograms/kg, intracerebroventricularly) within 10 min of arterial occlusion caused a significant (p less than 0.01) reduction in mean lesion size to 3.7 +/- 1.8% and stimulation of blood flow to the left ischaemic forebrain (60% above saline treated). Peripheral administration of RX77368 (1 mg/kg intraperitoneally) also significantly stimulated blood flow to the ischaemic forebrain and caused an apparent decrease in frequency of large infarcted areas of brain tissue, although mean lesion size was not significantly affected. These findings indicate that RX77368 ameliorates tissue damage in acute focal cerebral ischaemia. Such effects may be related to stimulation of cerebral blood flow.     

Vascular reactivity to carbon dioxide in the acute stage of cerebral infarction in rats

The effect of CO2 on the cerebral circulation was assessed 24 hours after induction of unilateral brain infarction performed in the rat by injecting radioactive calibrated 50 microns microspheres into the internal carotid artery. The intracerebral distribution of microspheres and regional cerebral blood flow were measured bilaterally in 8 brain regions. In control rats, increase in arterial pCO2 to about 80 mm Hg resulted in 30 to 100% increase in flow according to the area. Cerebral blood flow was also enhanced in the embolized rats, the basal values being multiplied by a factor 1.7 in the embolized hemisphere and by a factor 1.8 in the contralateral hemisphere. These results do not provide evidence for the existence of a "steal" phenomenon between the non infarcted and infarcted hemispheres.     

Regional cerebral blood flow changes during hypothermia

1. 1. When brain temperature was decreased from 38 to 22 °C using selective hypothermia, tissue blood flow decreased significantly in cerebral cortex, cerebellum, and thalamus, but did not significantly change in hypothalamic or brain stem tissue.

2. 2. A further decrease in brain temperature to 8 °C produced an increase in blood flow in all tissues except cerebral cortex compared to tissue blood flow measured at 22 °C. Compared to normothermic values, blood flow remained significantly decreased at 8 °C in cerebral and cerebellar cortex and was increased in brain stem.

3. 3. After rewarming, tissue blood flow returned to original baseline values in all tissues except cerebral cortex where blood flow was slightly but significantly decreased and brain stem, where blood flow was increased.

4. 4. These results indicate that the cerebrovascular effects of selective brain cooling are regionally specific. These changes appear to be due to both direct and indirect effects of cerebral hypothermia since brain tissue blood flow changes are apparent, compared to control values, after rewarming of the brain.

     

Effect of angiotensin II and peptide YY on cerebral and circumventricular blood flow

Angiotensin II and peptide YY (PYY) are putative neuro/humoral agents acting at several circumventricular regions. These peptides also constrict cerebral vessels. We examined the effect of acute intravenous infusion of saline, angiotensin II and peptide YY on local cerebral blood flow (14C-iodoantipyrine autoradiography) in the circumventricular and non-circumventricular brain regions of 17 conscious rats. No reductions in brain blood flow (28 regions) were observed although angiotensin II and PYY infusion elevated arterial blood pressure 15-25% without influencing heart rate, suggesting an increase in peripheral resistance. However, local blood flow was dependent on the peptide infused. During PYY infusion, blood flow was rather constant in the 20 non-circumventricular regions examined whereas an increase in blood flow and a slight decrease in cerebrovascular resistance occurred in the circumventricular regions. The area postrema exhibited the most pronounced changes--an elevation in blood flow of 44 +/- 11% and a reduction in resistance of 20 +/- 5% in comparison to that in control animals. During angiotensin II infusion, local cerebral blood flow was similar to that in controls and local cerebrovascular resistance was elevated. Thus, the local cerebral circulatory response to peptide administration was dependent on the location of the region examined (circumventricular or non-circumventricular) and on the vasoactive peptide infused.     

The regulation of the cerebral circulation in long lasting bradycardia

In the course of long lasting bradycardia in elderly patients, cardiac output will regularly diminish, circulation will slow down and signs of cerebral insufficiency may become manifest. The changes of cerebral circulation and its regulation were studied in 10 patients 61-74 years of age, with restricted cerebral regulatory capacity, suffering from permanent bradycardia. Cerebral blood flow was measured by using the venous isotope dilution technique by double punctures of the internal jugular vein. Hemispheric cerebral blood flow, cerebral O2 consumption and cerebral vascular resistance were determined during bradycardia and after termination of bradycardia by pacemaker. During long lasting bradycardia, cerebral blood flow and cerebral O2 consumption decreased, cerebral vascular resistance was elevated. After pacemaker implantation, cerebral blood flow and O2 consumption increased and cerebral vascular resistance decreased, approaching the normal value. The symptoms of cerebral insufficiency disappeared on improvement of the cerebral circulation.