The role of leukocytes in microcirculation dynamics in the norm and pathology

The physiological functions grow to be more perfect and complicated in the process of evolution. However, a developing function could display some evidence of regress and, in certain cases, it can trigger serious diseases including autoimmune ones. Conventionally, we refer to the above cases as to "errors" of evolution. The present case study deals with a negative factor of leukocytes in the cerebral microcirculation. Leukocytes were shown, experimentally, to inhibit the capillary blood flow owing to their big volume (2-2.5-fold more versus that of erythrocytes). An increasing trend to adhesion due to hypoxia is responsible for shaping of leukocytes' conglomerates, which cause the occlusion of venules and of the smallest cerebral veins. It entails the effect known as "no re-flow" resulting in death.     

The role of the cerebral cortex in the pathogenesis of hemolytic anemia

Summary The author studied the effect of acute disturbance of the higher nervous activity, caused by overstrain of the processes of excitation in the cerebral cortex, on the course of experimental hemolytic (phenylhydrazine) anemia. In animals with disturbed dynamics of the cortical function the course of anemia after administration of the same doses of hemolytic toxin was much more severe than in intact animals. With further development of disturbance of higher nervous activity the processes of blood regeneration became less intense. Moderate normochromic anemia develops in intact animals under the influence of disturbance of higher nervous activity. This anemia progresses with further development of disturbances of cortical dynamics. The results of these experiments demonstrate the role of cortical mechanisms in the pathogenesis of phenylhydrazine anemia. They confirm the literature data on the dependence of erythropoietic function of bone marrow on the functional condition of the cerebral cortex.Presented by Active Member AMN SSSR V. N. Chernigovskii     

Reduced GABA neuron density in auditory cerebral cortex of subjects with major depressive disorder

Although major depressive disorder (MDD) and schizophrenia (SZ) are closely associated with disrupted functions in frontal and limbic areas of cerebral cortex, cellular pathology has also been found in other brain areas, including primary sensory cortex. Auditory cortex is of particular interest, given the prominence of auditory hallucinations in SZ, and sensory deficits in MDD. We used stereological sampling methods in auditory cortex to look for cellular differences between MDD, SZ and non-psychiatric subjects. Additionally, as all of our MDD subjects died of suicide, we evaluated the association of suicide with our measurements by selecting a SZ sample that was divided between suicide and non-suicide subjects. Measurements were done in primary auditory cortex (area A1) and auditory association cortex (area Tpt), two areas with distinct roles in sensory processing and obvious differences in neuron density and size. In MDD, densities of GABAergic interneurons immunolabeled for calretinin (CR) and calbindin (CB) were 23–29% lower than non-psychiatric controls in both areas. Parvalbumin (PV) interneurons (counted only in area Tpt) showed a nominally smaller (16%) reduction that was not statistically significant. Total neuron and glia densities measured in Nissl stained sections did not show corresponding reductions. Analysis of suicide in the SZ sample indicated that reduced CR cell density was associated with suicide, whereas the densities of CB and other cells were not. Our results are consistent with previous studies in MDD that found altered GABA-associated markers throughout the cerebral cortex including primary sensory areas.     

Dopaminergic regulation of cerebral cortical microcirculation

Functional variations in cerebral cortical activity are accompanied by local changes in blood flow, but the mechanisms underlying this physiological coupling are not well understood. Here we report that dopamine, a neurotransmitter normally associated with neuromodulatory actions, may directly affect local cortical blood flow. Using light and electron-microscopic immunocytochemistry, we show that dopaminergic axons innervate the intraparenchymal microvessels. We also provide evidence in an in vitro slice preparation that dopamine produces vasomotor responses in the cortical vasculature. These anatomical and physiological observations reveal a previously unknown source of regulation of the microvasculature by dopamine. The findings may be relevant to the mechanisms underlying changes in blood flow observed in circulatory and neuropsychiatric disorders.     

The role of the cerebral cortex and subcortical centers in the regulation of blood cholesterol levels

Summary Development of a conditioned reflex to inhibition of respiration in the rabbit is accompanied by a decline of blood cholesterol. Feeding cholesterol to animals in a state of conditioned reflex activity did not result in hypercholesterinemia, while in control animals cholesterol feeding caused a rise of blood serum cholesterol. The cerebral cortex and subcortical formations are thus participating in the regulation of cholesterol metabolism.Preliminary data demonstrating deposition of lipoids in vascular walls of experimental rabbits, point to the possibility of vascular lipoidosis being caused by altered nervous regulation, the cholesterol blood level being normal.Presented by Active Member of the Academy of Medical Sciences USSR Professor P. S. Kupalov     

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.     

Vasomotion in the rat cerebral microcirculation recorded by laser-Doppler flowmetry

In the present study, changes in frequency and amplitude of the rhythmic variations (vasomotion) in blood flow in the intact cerebral circulation of the rat were investigated using laser-Doppler flowmetry (LDF) during stepwise decrease in mean arterial blood pressure (MABP) and hyper-and hypocapnia. Experiments were performed on 12 adult Sprague-Dawley rats of either sex, anaesthetized with α-chloralose. The rat's head was fixed on a stereotaxic frame and a small hole was made in the parietal bone but the dura and a thin inner bone layer were kept intact. The microvascular blood flow of the parietal cortex on the right or on both sides was continuously recorded by the laser-Doppler flowmeter (Periflux PF2B, Perimed, Stockholm, Sweden). The cerebral circulation of the rat exhibited vasomotion in control conditions with a frequency of 8–10 cycles per minute (cpm) and an amplitude of 5–10% of the cerebral blood flow (CBF). No significant changes in CBF could be detected when the MABP was above 60 mmHg, but it decreased significantly when MABP was reduced below 50 mmHg. However, during stepwise pressure reduction the vasomotion frequency decreased progressively while its amplitude showed a reversed U-shaped curve with a peak at 60–80 mmHg. During hypercapnia, the rhythmical oscillations showed a decrease in both frequency and amplitude, whereas during hypocapnia their frequency did not change but their amplitude increased. These results support the hypothesis that the vasomotion frequency might be dependent of the wall tension and cellular pH while its amplitude could be related to decreased tissue oxygenation.     

The serotonin innervation of the cerebral cortex in the rat—an immunohistochemical analysis

The serotonergic innervation of the cerebral cortex in the rat has been studied by immunohistochemistry employing an antibody directed against the neurotransmitter, serotonin. The dorsal raphe, median raphe and B9 cell groups contain intensely labelled neuronal perikarya. Bundles of large diameter axons suggestive of fibers of passage are observed in successive sections as they ascend through the midbrain tegmentum, medial forebrain bundle, diagonal band and supracallosal stria en route to the cortex. In addition, a lateral pathway to the cerebral cortex traversing the ansa peduncularis is visualized. All regions of the cerebral cortex appear to be innervated by serotonergic axons which have a distinctive morphology: they are fine (0.1–0.5 μm), varicose, and extremely convoluted. Serotonergic axons of passage are thicker and comparatively straight. Throughout the lateral neocortex, as well as in the anterior cingulate cortex, serotonergic axons form a densely arborizing plexus through all cortical layers. Contrary to earlier reports, based on histofluorescence, describing a sparse innervation of the cortex with most of the fibers found in the molecular layer, the present study reveals that the innervation is relatively uniform across all cortical layers. In most of the cortex the density of serotonin-containing axons exceeds that of noradrenergic fibers. A distinctive and different pattern of serotonin innervation is found in the posterior cingulate cortex (cytoarchitectonic field RSg): the serotonergic axons are restricted largely to lamina I and III. A restricted laminar pattern also characterizes the innervation of the hippocampus; dense axonal plexuses occur in the outer rim of the dentate hilus and in the stratum lacunosum-moleculare. The serotonergic afferents to the cortex appear to have at least two different modes of distribution, a relatively uniform pattern in the anterior cingulate and the lateral neocortex and a restricted, laminar pattern in the posterior cingulate and the hippocampus.The density and extent of the serotonin innervation is such that the raphe neurons may contact every cell in the cortex. The widespread arborization of serotonin axons contrasts with the spatially restricted termination of thalamic afferents. The distribution of serotonin-containing fibers also differs substantially from the terminal patterns of noradrenergic and dopaminergic fibers. The differences in axonal morphology and distribution amongst the monoamine afferents reflect differences in their contributions to cortical circuitry. The present findings indicate that the serotonin-containing neurons may exert a profound and global, but not necessarily uniform, influence upon cortical function.     

Effect of short-term cerebral ischemia on the mesenteric microcirculation in rats

The effect of cerebral ischemia produced by compression of both common carotid arteries on the mesenteric microcirculation was studied in experiments on rats. The extent and intensity of the microcirculatory disturbances were shown to depend on the duration of ischemia and of the postischemic period. The state of the systemic hemodynamics was compared with that of the mesenteric microcirculation. The possible mechanisms of the microcirculatory disturbances are discussed.Laboratory of General Pathology and Experimental Therapy, Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp. 9–12, July, 1979.     

基于RNA-seq的db/db小鼠大脑皮质的转录组学分析

目的通过对db/db和野生型(WT)小鼠大脑皮质组织全转录组学分析,探索参与调节2型糖尿病诱导的脑功能障碍的差异表达基因(DEGs)及相关通路和网络。方法取雄性野生型WT和db/db小鼠各9只,在第8和24周检测小鼠的体质量和血糖,之后收集动物大脑皮质进行全转录组测序(RNA-seq),并进行DEGs,GO、KEGG及蛋白互作网络分析。结果与WT组相比,db/db组大脑皮质发生变化的306个转录本中有178个表达上调,128个表达下调。DEGs中,43个上调(如Clcnka和Trim17),59个下调(如Arih1和Nectin-3)。蛋白互作网络图中的13个枢纽基因均下调,且大多属于线粒体编码家族。同时,db/db小鼠在多项GO富集类别中具有显著差异,如细胞过程、细胞部分等。此外,KEGG功能富集结果显示DEGs在代谢、帕金森病(PD)、阿尔茨海默病(AD)等相关通路中高度富集,且这些富集通路中的DEGs主要影响了线粒体氧化磷酸化过程。结论揭示了2型糖尿病与中枢神经系统损伤之间的关系及潜在的相关基因、通路及网络。     

Evidence for a neurotropic role of noradrenaline neurons in the postnatal development of rat cerebral cortex

Summary The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1–4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, an 80% reduction after three doses, and a 97–98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.     

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     

The role of basal forebrain neurons in tonic and phasic activation of the cerebral cortex.

The basal forebrain and in particular its cholinergic projections to the cerebral cortex have long been implicated in the maintenance of cortical activation. This review summarizes evidence supporting a close link between basal forebrain neuronal activity and the cortical electroencephalogram (EEG). The anatomy of basal forebrain projections and effects of acetylcholine on cortical and thalamic neurons are discussed along with the modulatory inputs to basal forebrain neurons. As both cholinergic and GABAergic basal forebrain neurons project to the cortex, identification of the transmitter specificity of basal forebrain neurons is critical for correlating their activity with the activity of cortical neurons and the EEG. Characteristics of the different basal forebrain neurons from in vitro and in vivo studies are summarized which might make it possible to identify different neuronal types. Recent evidence suggests that basal forebrain neurons activate the cortex not only tonically, as previously shown, but also phasically. Data on basal forebrain neuronal activity are presented, clearly showing that there are strong tonic and phasic correlations between the firing of individual basal forebrain cells and the cortical activity. Close analysis of temporal correlation indicates that changes in basal forebrain neuronal activity precede those in the cortex. While correlational, these data, together with the anatomical and pharmacological findings, suggest that the basal forebrain has an important role in regulating both the tonic and the phasic functioning of the cortex.