Cerebrovascular effects of met- and leu-enkephalins

Met- and leu-enkephalines have a two-phase influence on the brain blood supply: initial short-term blood flow increase is replaced by the decrease of cerebral blood flow. Enkephalines are established to possess a pronounced depressive influence on neurogenic spasms of cerebral vessels and somatosympathetic and vasomotor reflex both under systemic administration and administration into brain lateral ventricles. Bicucullin has no effect on leuenkephaline action on cerebral circulation and its nervous control, while naloxone either removes or reduces the effects. Hence, opiate receptors take part in the realization of cerebrovascular effects of opioid peptides. The data obtained show the brain opioid system involvement in the regulation of brain circulation.     

Mechanism of the cerebrovascular effect of piracetam

Piracetam produces a more pronounced effect on cerebral circulation disturbed by hemorrhagic shock as compared with intact animals. Piracetam has a depressant effect on the nervous regulation of cerebral circulation by suppressing the reflex constriction of the vessels in both arterial systems of the brain. The cerebrovascular effects of piracetam are not mediated through the GABAergic bicuculline-sensitive mechanisms, which is supported by experiments where the drug exhibits its effects under the blockade of GABA receptors.     

Adrenomedullin in the cerebral circulation.

The central nervous system requires an effective autoregulation of cerebral circulation in order to meet the critical and unusual demands of the brain. In addition, cerebral microvessels has a unique feature, the formation of the blood-brain barrier, which contributes to the stability of the brain parenchymal microenvironment. Many factors are known to be involved in the regulation of cerebral circulation and blood-brain barrier functions. In the last few years a new potential candidate, adrenomedullin, a hypotensive peptide was added to this list. Adrenomedullin has a potent vasodilator effect on the cerebral vasculature, and it may be implicated in the pathologic mechanism of cerebrovascular diseases. In this review, we describe current knowledge about the origin and possible role of adrenomedullin in the regulation of cerebral circulation and blood-brain barrier functions.     

Effect of the nitro analog of tetrapeptidamide and morphine on the cerebral blood supply

A tetrapeptidamide nitroanalog and morphine produced an unmarked and short-lived increase in cerebral circulation, determined by the reduction of the vascular tone in both arterial brain systems. The tetrapeptidamide nitroanalog and morphine exerted a pronounced depressant effect on the nervous regulation of cerebral circulation by inhibiting the reflex constriction of the cerebral vessels. These effects of the drugs also occurred under blockade of GABA receptors. This indicates no relationship between the properties of the tetrapeptidamide nitroanalog and morphine and bicuculline-sensitive GABAergic processes.     

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.     

Morphologic changes in the sensomotor cortex in experimental neurosis

Disturbances of higher nervous activity (experimental neurosis) are attended with morphological changes of blood circulation in the sensorimotor area of the cerebral cortex, corresponding to distonic vascular disorders, as well as with hypoxic and neuroglial changes. Observed changes in the nervous tissue also reflect adaptive and defensive mechanisms of the brain (in rabbits).     

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.     

Apparent diffusion time of oxygen from blood to tissue in rat cerebral cortex: implication for tissue oxygen dynamics during brain functions.

To investigate the dynamics of tissue oxygen demand and supply during brain functions, we simultaneously recorded Po(2) and local cerebral blood flow (LCBF) with an oxygen microelectrode and laser Doppler flowmetry, respectively, in rat somatosensory cortex. Electrical hindlimb stimuli were applied for 1, 2, and 5 s to vary the duration of evoked cerebral metabolic rate of oxygen (CMR(O(2))). The electrical stimulation induced a robust increase in Po(2) (4-9 Torr at peak) after an increase in LCBF (14-26% at peak). A consistent lag of approximately 1.2 s (0.6-2.3 s for individual animals) in the Po(2) relative to LCBF was found, irrespective of stimulus length. It is argued that the lag in Po(2) was predominantly caused by the time required for oxygen to diffuse through tissue. During brain functions, the supply of fresh oxygen further lagged because of the latency of LCBF onset ( approximately 0.4 s). The results indicate that the tissue oxygen supports excess demand until the arrival of fresh oxygen. However, a large drop in Po(2) was not observed, indicating that the evoked neural activity demands little extra oxygen or that the time course of excess demand is as slow as the increase in supply. Thus the dynamics of Po(2) during brain functions predominantly depend on the time course of LCBF. Possible factors influencing the lag between demand and supply are discussed, including vascular spacing, reactivity of the vessels, and diffusivity of oxygen.     

Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease.

The brain is critically dependent on a continuous supply of blood to function. Therefore, the cerebral vasculature is endowed with neurovascular control mechanisms that assure that the blood supply of the brain is commensurate to the energy needs of its cellular constituents. The regulation of cerebral blood flow (CBF) during brain activity involves the coordinated interaction of neurons, glia, and vascular cells. Thus, whereas neurons and glia generate the signals initiating the vasodilation, endothelial cells, pericytes, and smooth muscle cells act in concert to transduce these signals into carefully orchestrated vascular changes that lead to CBF increases focused to the activated area and temporally linked to the period of activation. Neurovascular coupling is disrupted in pathological conditions, such as hypertension, Alzheimer disease, and ischemic stroke. Consequently, CBF is no longer matched to the metabolic requirements of the tissue. This cerebrovascular dysregulation is mediated in large part by the deleterious action of reactive oxygen species on cerebral blood vessels. A major source of cerebral vascular radicals in models of hypertension and Alzheimer disease is the enzyme NADPH oxidase. These findings, collectively, highlight the importance of neurovascular coupling to the health of the normal brain and suggest a therapeutic target for improving brain function in pathologies associated with cerebrovascular dysfunction.     

Post-irradiation changes in the content of phospholipids and cyclic nucleotides in the mouse brain]

The effect of ionizing radiation (5, 20, 100, 200 and 400 Gy) on the content of phospholipids and cyclic nucleotides in the brain tissue has been studied in experiments on albino mice. During the development of evident behavioural disturbances in irradiated mice (2 h after irradiation with doses 100-400 Gy), significant changes were observed in the content of phosphatidylinositides and cyclic GMP. These changes may account for disturbances in the function of the central nervous system during cerebral forms of acute radiation injury.     

The blood-brain barrier in a reptile, Anolis carolinensis

An electron microscopic study was made of the ultrastructure and permeability of the capillaries in the cerebral hemispheres of the lizard, Anolis carolinensis. The brain of Anolis is vascularized by a loop-type pattern consisting exclusively of arteriovenous capillary loops. The ultrastructure of the endothelium and the arrangement of the various layers from the capillary lumen to the central nervous tissue is similar to that of mammals. The endothelial cells form a continuous layer around the lumen and are joined by tight interendothelial junctions. The basal lamina of the endothelium is also continuous and encloses pericyte processes. The cells of the nervous tissue rest directly on the basal lamina of the capillary and are separated from each other by a 200 Å space. Intravenously injected horseradish peroxidase (MW 40,000) and ferritin (MW 500,000) were used to study the permeability of the capillaries. The entry of horseradish peroxidase and ferritin into the intercellular spaces of the brain is restricted by the tightness of the interendothelial junctions. No vesicular transport of either tracer occurs; however, ferritin does enter the endothelial cells in vacuoles. No tracer molecules are present in the basal lamina, pericytes, or nervous tissue. The different responses of the endothelial cell to the tracers used in this study suggest that endocytotic activities of endothelial cells involve different processes. Vacuoles formed by marginal folds, vacuoles formed by endothelial surface projections or deep invaginations of the plasma membrane, 600–800 Å vesicles, and coated vesicles all seem to differ in the nature of the substances which they endocytose.     

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.     

综述与专论: 高压氧疗法治疗脑缺血的相关机制

脑缺血是指大脑各部分血液供应不足导致脑组织缺血缺氧，进而导致密集缺血区脑组织出现不可逆的损伤坏死，其高致残率、高死亡率会对患者及其家庭造成严重的伤害。在脑缺血发生后，及时采取一定的治疗措施控制梗死灶的大小，并挽救半暗带中的细胞是脑缺血预后的关键。高压氧疗法是针对脑缺血的一种潜在治疗方法，在近年来得到了越来越广泛的关注和研究，本文旨在综述近年来国内外关于高压氧疗法治疗脑缺血的相关机制及研究进展，为脑缺血患者的治疗和预后提供新思路。     

O2 transport in cerebral microregions (mathematical simulation)

The effects of the circulation rate in capillaries, the intensity of O2 consumption by nerve cells and the capillary network density on the O2 tension distribution in the cerebral cortex have been studied, utilizing a mathematical model simulating actual neuron-capillary relationships. The model has been written as a system of equations in partial derivatives, its solution obtained by the net-point method. Regulatory variations of the capillary circulation rate in certain cerebral microregions have been shown to ensure similar changes in oxygen supply throughout the region. A drop of the pO2 level in a cerebral microregion with a rising O2 consumption by nerve cells is shown to be due, by 75 percent, to the increase of O2 consumption and by 25 percent, to the lower pO2 in the capillaries. Conversely, an increase in pO2 in microregions resulting from a lower O2 consumption by neurons is due by 75 percent, to a pO2 rise in capillaries and by 25 percent, at the expense of an O2 consumption decrease. In cerebral regions differing in capillary network density by 20 percent, changes in the conditions for oxygen supply to tissue are due by 1/3 to pO2 variations in the capillaries and by 2/3 to alterations in the diffusion distances.     

Slow Rhythmic Oscillations within the Human Cranium: Phenomenology, Origin, and Informational Significance

Slow rhythmic oscillations in the human cranial cavity were studied using two noninvasive methods: the bioimpedance method (volume ratios between liquid media in the cranial cavity) and transcranial ultrasound Doppler echography (variation in the blood flow in the middle cerebral artery). The combination of these methods made it possible to estimate the intracranial hemodynamics. Simultaneous recording of these parameters and their spectral analysis were carried out in healthy subjects and patients with intracranial hypertension syndrome and disturbed cerebrospinal fluid (CSF) flow. The parameters were recorded at rest and immediately after manual (osteopathic) correction. The recording and analysis were performed using a Macintosh-IIsi PC and the Chart-3.52, Cricket Graph-3.32, and Canvas-3.5 software. It was found that slow oscillations of the bioimpedance (BIM) in the frequency range 0.08–0.2 Hz were of intracranial origin and were related to the mechanisms of regulation of the blood supply to and oxygen consumption by cerebral tissue, as well as with the dynamics of the CSF circulation.     

Red blood cell velocity and oxygen tension measurement in cerebral microvessels by double-wavelength photoexcitation.

Because the regulation of microcirculation in the cerebral cortex cannot be analyzed without measuring the blood flow dynamics and oxygen concentration in cerebral microvessels, we developed a fluorescence and phosphorescence system for estimating red blood cell velocity and oxygen tension in cerebral microcirculation noninvasively and continuously with high spatial resolution. Using red blood cells labeled with fluorescent isothiocyanate to visualize red cell distribution and using the oxygen quenching of Pd-meso-tetra-(4-carboxyphenyl)-porphyrin phosphorescence to measure oxygen tension enabled simultaneous measurement of blood velocity and oxygen tension. We examined how the measurement accuracy was affected by the spatial resolution and by the excitation laser light passing through the targeted microvessel and exciting the oxygen probe dye in the tissue beneath it. Focusing the excitation light into the microvessel stabilized the phosphorescence lifetime at each spatial resolution; moreover, it greatly reduced phosphorescence from the brain tissue. Animal experiments involving acute hemorrhagic shock demonstrated the feasibility of our system by showing that the changes in venular velocity and oxygen tension are synchronized to the change in mean arterial pressure. Our system measures the red cell velocity and oxygen concentration in the cerebral microcirculation by using the differences in luminescence and wavelength between fluorescence and phosphorescence, making it possible to easily acquire information about cerebral microcirculatory distribution and oxygen tension simultaneously.     

Anaerobic shift of energy metabolism in the mouse brain during the recovery period in acute radiation sickness

Three months after whole-body irradiation of mice with a sublethal dose of 5 Gy a study was made of some indices of energy metabolism like tissue respiration, oxidative phosphorylation, and formation of lactic acid in the survived brain homogenate. Revealed were the diminution of coupling of tissue respiration of oxidative phosphorylation, the rate of oxygen consumption and the level of cyano-resistant respiration being constant, the increase in the rate of glycolysis in anaerobic and particularly, in aerobic conditions, and reduction of the Pasteur and Crabtree effects. The above mentioned changes in the brain energy metabolism seem to be a manifestation of the process of the reduced metabolism formation in the nervous tissue at the remote times after irradiation.     

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.     

GABA system as a factor facilitating the development of compensation of disordered cerebral hemodynamics

Shifts in the system of GABA transformation in ischemia and specific inhibition of GABA-transaminase under conditions of quantitative measurement of the blood circulation by means of hydrogen clearance permitted to establish a definite association between the increased GABA level in the brain and the tissues of the wall of its arteries, and the development of compensation of disturbed cerebral circulation. Consequently, one of the principal manifestations of an increased amount of endogenous GABA in deficiency of the brain blood supply was GABA capacity to improve the cerebral circulation.