Innervation of the cerebral vasculature

With the development of specific antibodies to vasoactive peptides and application of immunohistochemistry and radioimmunoassay methods, knowledge of vascular innervation has grown rapidly. In the cerebral circulation, four possible neurotransmitters are present: norepinephrine, acetylcholine, vasoactive intestinal peptide (VIP), and substance P. There is a dense adrenergic innervation of cerebral arteries, but contractile responses to nerve stimulation or circulating catecholamines are relatively small both in vitro and in vivo. Recent studies using radioligand binding techniques indicate a lack of specific³H-prazosin binding in cerebral arteries, in contrast to other vascular beds. Thus a lack of α₁-adrenergic receptors in cerebral arteries may account for weak responsiveness to sympathetic stimulation. Both VIP and acetylcholine may be vasodilator neurotransmitters, but blockade of cholinergic responses does not alter neurogenic vasodilation. The lack of specific VIP antagonists hampers efferots to explore this system more fully. Substance P-containing nerves are affected by capsaicin, supporting the hypothesis that these are primary sensory afferents, perhaps mediating pain. Future work in this area may focus on defining the pathways of these nerves and exploring the role of co-transmitters and possible interactions between nerves. With this basic information, experiments can be designed to elucidate more clearly the functional roles these nerves play. Established Investigator of the American Heart Association with funds contributed in part by the Arizona Affiliate.     

Correlation between cerebral blood volume and cerebral blood flow in the cat

Summary Blood flow and blood volume were measured simultaneously in the same cerebral region in anaesthetized cats with controlled respiration. The measurements were made with the same scintillation-detector, using the freely diffusible indicator ¹³³ Xenon for flow determinations and the intra-vascular indicator RISA (¹³¹I) for volume recordings. A very high correlation was found between volume and flow changes (r = .96, p < 0.001). This finding indicates that variations of regional cerebral blood volume are accompanied by proportional blood flow changes.Attaché de recherche au C.N.R.S., Laboratoire de Neurophysiologie, Hopital Henri Rouselle, Paris, France.     

Dehydroepiandrosterone and the cerebral functions

Of all steroidal hormones, dehydroepiandrosterone (DHEA) and its sulphate form, DHEAS, are synthesized by the adrenal glands in the biggest quantities. In this review the authors consider the ways of the synthesis of the neurosteroids, possible mechanisms of the regulation of these processes, and their dynamics under stressful conditions. The paper presents analysis of experimental and clinical data on the role of DHEAS in the manifestation of different cerebral functions. The authors pay special attention to the results of substitutive therapy with DHEA(S) in patients with such CNS functional disorders, as Alzheimer's disease, depression, age-relative memory and sleep disturbances, etc.     

Preserved dynamic cerebral autoregulation in the middle cerebral artery among persons with migraine

Migraine affects the autonomous nervous system and a recent investigation has also proposed a severe disturbance of dynamic cerebral blood flow regulation in the middle cerebral artery during spontaneous blood pressure oscillations. This study investigates whether dynamic cerebral autoregulation is impaired in persons with migraine among a normal cohort. Out of 94 adults studied to establish normal values for dynamic autoregulation, 19 suffered from migraine according to IHS criteria (10 of them with aura). Transcranial Doppler sonography and fingerplethysmography were used to determine dynamic autoregulation of both middle cerebral arteries following spontaneous low frequency (0.06–0.12 Hz) blood pressure fluctuations (phase and gain of transfer function, correlation coefficient indices Dx and Mx). No significant differences were found for the low frequency variability of blood pressure (power spectral density) and various indices of dynamic cerebral autoregulation between persons with and without migraine. Moreover, no differences were observed between persons with migraine, with and without aura. This study based on a normal cohort does not support the presence of generally impaired cerebral autoregulation dynamics in persons with migraine. Future studies should focus on posterior circulation and particular cerebellar autoregulation.     

Dynamic interactions between the cerebral hemispheres

The cortical areas of the two hemispheres interact via the corpus callosum. This paper reviews recent findings in animals and man, showing that the visual areas of the two hemispheres control each other’s dynamics. The interaction is stimulus-dependent and stimulus-specific. It consists of both excitatory and inhibitory inputs controlling the formation of synchronous neuronal assemblies across and within the hemispheres. The findings are consistent with the geometry of callosal axons and their inferred computational properties. These are the first findings to suggest a direct relationship between the geometry of cortical connections, and the formation of stimulus-driven synchronous neuronal assemblies.     

Modeling perfusion in the cerebral vasculature

The constant perfusion of a human organ with nutrients and oxygen demands a robust regulatory mechanisms in the face of normal day-to-day pressure variations in the vasculature. The brain, in a similar manner to the heart requires this mechanism to be extremely quick acting, relative to other ways of altering perfusion such as varying systemic blood pressure, since oxygen depravation in the tissues of the brain can be tolerated for only of the order of tens of seconds before significant damage can be done.In recent years computational models, and it must be noted computer architecture have evolved to an extent where mathematicians and engineers can play a large part in discovering how the brain functions physiologically as well as investigating pathological conditions. This review will look at a number of increasingly complex computational models of blood flow to the brain and how variations in arterial geometry can influence the perfusion in the cerebral vasculature. Although these models have provided an insight into complex mechanisms the research area is densely populated with important questions that perhaps only computer models can answer. The review will indicate possible areas of investigation.     

Sentence processing in the cerebral cortex

Human language is a unique faculty of the mind. It has been the ultimate mystery throughout the history of neuroscience. Despite many aphasia and functional imaging studies, the exact correlation between cortical language areas and subcomponents of the linguistic system has not been established. One notable drawback is that most functional imaging studies have tested language tasks at the word level, such as lexical decision and word generation tasks, thereby neglecting the syntactic aspects of the language faculty. As proposed by Chomsky, the critical knowledge of language involves universal grammar (UG), which governs the syntactic structure of sentences. In this article, we will review recent advances made by functional neuroimaging studies of language, focusing especially on sentence processing in the cerebral cortex. We also present the recent results of our functional magnetic resonance imaging (fMRI) study intended to identify cortical areas specifically involved in syntactic processing. A study of sentence processing that employs a newly developed technique, optical topography (OT), is also presented. Based on these findings, we propose a modular specialization of Broca's area, Wernicke's area, and the angular gyrus/supramarginal gyrus. The current direction of research in neuroscience is beginning to establish the existence of distinct modules responsible for our knowledge of language.     

On regeneration of the cerebral cortex

Summary In order to ascertain the possibility of structural regeneration in the cortical areas of the cerebral hemispheres, the cortex of the sigmoid convolution was extirpated in puppies aged 10 and 14 days. These animals were then sacrificed 2 and 7 months after the operation. Their brains were fixed in 10% formalin and sections of the material were stained with cresyl violet. The site of the defect was clearly visible macroscopically. However, its size was considerably less than at the time of the operation. Due to growth of the brain, the edges of the injured area moved over the defect, closing it over and joining each other. This was quite distinct microscopically. However, where the size of the injury was enlarged by hematoma and reached the lateral ventricle, no closing in of the tissue or juncture of the edges was observed. Thus, in the opinion of the author, there was no replacement of the brain matter by new matter, but there only occurred superposition and juncture of the adjacent areas, which created the appearance of tissue regeneration.Presented by Active Member of the Academy of Medical Sciences, USSR B. N. Klosovskii Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 3, pp. 105–108, March, 1964     

Glial regulation of the cerebral microvasculature

The brain is a heterogeneous organ with regionally varied and constantly changing energetic needs. Blood vessels in the brain are equipped with control mechanisms that match oxygen and glucose delivery through blood flow with the local metabolic demands that are imposed by neural activity. However, the cellular bases of this mechanism have remained elusive. A major advance has been the demonstration that astrocytes, cells with extensive contacts with both synapses and cerebral blood vessels, participate in the increases in flow evoked by synaptic activity. Their organization in nonoverlapping spatial domains indicates that they are uniquely positioned to shape the spatial distribution of the vascular responses that are evoked by neural activity. Astrocytic calcium is an important determinant of microvascular function and may regulate flow independently of synaptic activity. The involvement of astrocytes in neurovascular coupling has broad implications for the interpretation of functional imaging signals and for the understanding of brain diseases that are associated with neurovascular dysfunction.     

Charge-related alterations of the cerebral endothelium

In a short-term rat brain perfusion model, the luminal surface of cerebral endothelium was exposed to the following solutions: (a) the polycation protamine sulfate (PS) in a dose of 50, 100, and 500 micrograms/ml for 1 or 2 minutes; (b) PS in a dose of 100 micrograms/ml (or 500 micrograms/ml) for 1 or 2 minutes followed by the polyanion heparin in an equivalent dose of 12 units/ml (or 60 units/ml) for 1 or 2 minutes; (c) heparin alone for 1 or 2 minutes, and (d) Krebs-Ringer-bicarbonate solution as control for 1, 2, or 4 minutes. We studied in the cerebral endothelium: (a) structural alterations by electron microscopy, (b) permeability changes to horseradish peroxidase (HRP) by light and electron microscopy, and (c) charge alterations of luminal surface visualized with colloidal iron at pH 1.8 by electron microscopy. We found that: (a) PS resulted in extravasation of HRP throughout the perfused hemispheres in a time- and dose-dependent fashion. In this experimental group, colloidal iron binding decreased on the luminal surface of the cerebral blood vessels; (b) heparin perfusion following PS reversed the colloidal iron staining but failed to prevent the blood barrier opening to HRP; (c) heparin perfused alone also induced extravasation of HRP in the treated brain hemispheres; (d) in Krebs-Ringer-bicarbonate-perfused control brains extravasation of HRP was encountered only in occasional vascular segments. In all brain hemispheres showing tracer extravasation, electron microscopy revealed HRP reaction product in compartments of endothelial tight junctions suggesting opening of interendothelial routes as the structural basis of blood-brain barrier opening. Endothelial cell death reflected by swelling and influx of HRP into endothelial cytoplasm in PS- and/or heparin-perfused hemispheres was probably an additional mechanism explaining tracer extravasation into the neuropil. Our results indicate a correlation between the effect of polycation PS and a decrease in the anionic sites of cerebral endothelium. The relationship between charge alteration and barrier opening in the short-term rat brain perfusion model is not clear.     

Compensatory adjustment in blood flow of the rabbit cerebral cortex during graded cerebral ischemia

The role of the bilateral internal carotid and vertebral arteries in supplying cerebral cortex tissue blood flow (CTF) and the compensatory adjustment in CTF during graded cerebral ischemia were studied to determine the relationship to the increase in systemic arterial pressure (SAP) in anesthetized rabbits. CTF was recorded continuously by using Peltier stacks placed on both sides of the surface of the cerebral parietal cortex. Occlusion of the bilateral internal carotid arteries caused a decrease in CTF to 81.9% of the control value for the right hemisphere, and 83.5% of that for the left. Occlusion of the bilateral vertebral arteries produced no appreciable change in CTF. Compensatory adjustment in CTF was incomplete, i.e., CTF was reduced to a lower level, in the range of internal carotid flow (ICF) from 2 to 6 ml/min, and was severely reduced at 1 and 0 ml/min. The relationships between ICF and SAP, and ICF and CTF formed rectangular hyperbolic curves. No significant difference was observed between the decreases in CTF obtained before and after bilateral sectioning of the cervical sympathetic trunks. The relationship between SAP and CTF was described by a linear regression equation. These results indicate that the internal carotid arteries play a much more important role in supplying CTF than the vertebral arteries, that SAP rises in inverse proportion to the decrease in CTF, and that the cervical sympathetic trunks do not influence the compensatory adjustment in CTF caused by cerebral ischemia.     

高血脂对大鼠脑缺血再灌注损伤后大脑皮质基质金属蛋白酶9表达的影响

目的:研究高血脂对脑缺血再灌注损伤后大脑皮质基质金属蛋白酶9(MMP-9)表达的影响,探讨高血脂加重脑缺血再灌注损伤的机制。方法:高脂饲料喂养和线栓法分别建立高血脂动物模型和局灶性脑缺血再灌注模型,采用蛋白印迹、TTC染色、EB染色以及神经行为学评分,检测MMP-9的表达和脑梗死体积、血脑屏障通透性及神经行为的变化。结果:与假手术组比较,单纯脑缺血再灌注组和高血脂合并脑缺血再灌注组大脑皮质MMP-9表达增加,再灌注2 h时开始增加,24 h时达高峰,48、72 h时降低。相同再灌注时间点,与单纯脑缺血再灌注组比较,高血脂合并脑缺血再灌注组大脑皮质MMP-9表达明显增加,且脑梗死体积、血脑屏障通透性及神经行为评分均明显升高。结论:高血脂可通过上调大脑皮质MMP-9的表达而加重脑缺血再灌注损伤。     

Localization in the cerebral cortex of the rat

Summary The work was carried out on 19 rats. Positive and negative conditioned reflexes to sound and light, and conditioned changing over of different reflexes to sound and light were elaborated. The occipital cortex was removed after these reflexes had become established. Changes in the conditioned reflex activity occurred after the operation, and demonstrated that in rats visual function is localized in the occipital cortex which is involved not only in the solution of a simple problem, but also in discrimination; it appears also that it is concerned in the change-over of conditioned reflexes. Localizatinn of this function could be demonstrated also after a second injury to the cortex. These results show that a test may be made of the diaschisis theory, support obtained for it in opposition to Lashley's view. After the operation, the rats became more excitable, and their power to differentiate was considerably disturbed. It would appear that the main cause of the marked disturbance of the habit of running in the maze was the development of spontaneous activity as a result of injury to the cerebral cortex.Department of Normal Physiology (Head, Professor G. I. Kositskii, N. I. Pirogov II Moscow Medical Institute) Director, Corresponding Member USSR Academy of Sciences E. A. Asratyan. (Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi i Meditsiny, Vol. 33, No. 6, pp. 19–24, June, 1963