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Basal forebrain efferents reach the whole cerebral cortex of the cat.

Efferent projections from the basal forebrain to the cat's cerebral cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cerebral cortex of 51 cats were injected with small amounts of horseradish peroxidase. The entire basal forebrain was screened for labeled neurons. Following all injections, retrogradely labeled neurons could be detected in either the medial septum, or the vertical and horizontal limb of the diagonal band of Broca, or the substantia innominata, or in several of these structures. All three basal forebrain structures project heavily to allocortical regions, but only weakly to neocortical regions. An exception is the medial prefrontal cortex which is densily innervated by the substantia innominata (i.e., comparably dense as allocortical regions are innervated by the substantia innominata). Large injections into he basal temporal cortex (including the perirhinal cortex) and into the insular cortex also led to a considerable number of labeled cells in the substantia innominata. The results indicate a widespread innervation of the cat's cerebral cortex by the basal forebrain. This diffuse projection to the cortex has recently been found also in monkeys and rats. Anatomical and functional implications of these projections in the cat are discussed and related to findings in other species.

Animals↗

Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells.

The diverse array of neurons and glia in the mammalian cerebral cortex arises from proliferating cells of the ventricular zone that surrounds the lateral ventricles of the developing brain. A fundamental but unresolved question is whether the individual cells of the ventricular zone are committed to producing progeny of only one particular phenotype or whether they generate progeny of more than one phenotype. We have begun to address this question by asking if individual cells of the ventricular zone generate exclusively neurons or glia at the onset of cortical neurogenesis in the rat. To assess the phenotypes of cells derived from a common progenitor cell, retroviral-mediated gene transfer was used to introduce the reporter gene, Escherichia coli beta-galactosidase, into ventricular zone cells at embryonic day 15 or 16. We used histochemistry to reveal beta-galactosidase-expressing cells in the mature rat cerebral cortex. Isolated clusters of beta-galactosidase-expressing cells, presumably clones, were identified in serial sections. Since the histochemical reaction product is electron dense, each cell could be examined at the ultrastructural level and assigned definitively to one of the major classes of cells in the cerebral cortex on the basis of well-established morphological criteria. This approach overcomes the problems of cell type identification encountered with light microscopy, where it is not always possible to distinguish between different cell phenotypes. We found that virtually all clones contained cells of exclusively one type: either all astrocytes, all oligodendrocytes, or all neurons. Furthermore, each particular cell type exhibited a different pattern and intensity of staining. The neuronal clones, with one exception, were composed of either all pyramidal cells (projection neurons), or all nonpyramidal cells (interneurons). The size and composition of neuronal clones did not seem related to their position in the cerebral cortex. Collectively, our observations indicate that separate progenitor cells exist for pyramidal neurons, nonpyramidal neurons, astrocytes, and oligodendrocytes. The striking phenotypic homogeneity in the clones arising from individual progenitor cells suggests that by the onset of cortical neurogenesis, at least some lineage restrictions have already occurred among the precursor cell population. Thus, our results suggest that lineage may play a pivotal role in determining some of the functionally important phenotypic attributes of cells in the cerebral cortex.

Animals↗

Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat.

1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-HT release in the caudate nucleus and increases it 3 fold in the cerebral cortex. The effects of the electrical stimulation of the raphe are potentiated by chlorimipramine. 3. Brain 5-HT release is greatly increased by morphine hydrochloride (6 mg/kg i.v.) and by physostigmine (100 microgram/kg i.v.), but not by DL-DOPA (50 mg/kg i.v.). 4. It is suggested that the 5-HT releasing action of physostigmine can contribute to some of its pharmacological effects such as the analgesic effect so far attributed exclusively to its indirect cholinomimetic activity. 5. The 5-HT releasing action of physostigmine seems unrelated to its anticholinesterase activity.

Animals↗

[Assessment of hemodynamics in the cerebral cortex in newborn infants].

Determinations of blood velocity in vessels of cerebral cortex have been done using a 20 MHz impulse Doppler unit. In comparison we registered the blood flow pulsation curves at the anterior cerebral artery with aid of a 5 MHz-cw-Doppler system. The peripheral resistance index was calculated and it could be proved a strong correlation between the results of the anterior cerebral artery and the vessels of cerebral cortex. Another study showed that the results of the method could be reproduced. The problem of the impulse Doppler examinations of cerebral cortical vessels is the fact, that the exact topography of the vessels examined cannot be defined exactly.

Blood Flow Velocity↗

Control of glycolysis in cerebral cortex slices.

1. Intracellular concentrations of intermediates and cofactors of glycolysis were measured in guinea-pig cerebral cortex slices incubated under varying conditions. 2. Comparison of mass-action ratios with apparent equilibrium constants for the reactions of glycolysis showed that hexokinase, phosphofructokinase and pyruvate kinase catalyse reactions generally far from equilibrium, whereas phosphoglucose isomerase, aldolase, phosphoglycerate kinase, phosphoglycerate mutase, enolase, adenlyate kinase and creatine phosphokinase are generally close to equilibrium. The possibility that glyceraldehyde 3-phosphate dehydrogenase may catalyse a ;non-equilibrium' reaction is discussed. 3. Correlation of changes in concentrations of substrates for enzymes catalysing ;non-equilibrium' reactions with changes in rates of glycolysis caused by alteration of the conditions of incubation showed that hexokinase, phosphofructokinase, pyruvate kinase and possibly glyceraldehyde 3-phosphate dehydrogenase are subject to metabolic control in cerebral cortex slices. 4. It is suggested that the glycolysis is controlled by two regulatory systems, the hexokinase-phosphofructokinase system and the glyceraldehyde 3-phosphate dehydrogenase-pyruvate kinase system. These are discussed. 5. It is concluded that the rate of glycolysis in guinea-pig cerebral cortex slices is limited either by the rate of glucose entry into the slices or by the hexokinase-phosphofructokinase system. 6. It is concluded that addition of 0.1mm-ouabain to guinea-pig cerebral cortex slices causes inhibition of either glyceraldehyde 3-phosphate dehydrogenase or phosphoglycerate kinase or both, in a manner independent of the known action of ouabain on the sodium- and potassium-activated adenosine triphosphatase.

Animals↗

Tissue printing of astroglial interlaminar processes from human and non-human primate cerebral cortex.

Astroglial interlaminar processes are unique features of the cerebral cortex of adult primates, including man. The functional role of these processes in the primate cerebral cortex is largely unknown. The development and standardization of procedures that could maximize the utilization of primate brain samples is required for the experimental analysis of the individual and collective dynamic properties of interlaminar glial processes. With this aim and in order to assess the relative stability of these glial processes in ex vivo conditions, "tissue printing" procedures were applied. "Tissue printing" allows for the acute transfer of cellular elements from fresh tissue onto an artificial substrate. Human, monkey (Cebus apella), and rat brain samples were subjected to "tissue printing" procedures followed by cell culture and immunohistochemistry. For the purpose of comparing the efficiency of this procedure on the transfer of other long glial processes, "tissue prints" of radial glial processes from neonatal rats and of Bergmann glia from cerebellar samples of adult rats were included. Nitrocellulose (with and without added fibronectin or laminin) produced the best attachment results. Interlaminar processes were not modified following 24-h incubation in a cell culture medium, with the addition of agents known to modify astroglial morphotypes in vitro (cyclic adenosine monophosphate, 40 mM K(+), or fetal calf serum). It is concluded that glia with interlaminar processes can be detached from fresh tissue using "tissue printing" procedures, can be maintained for at least 24 h in standard culture conditions, and showed a stable morphological phenotype.

Animals↗

Age-dependent changes in the oxygen consumption of the cerebral cortex, hypothalamus, hippocampus, and amygdaloid in rats.

The oxygen consumption of the cerebral cortex, hypothalamus, hippocampus, and amygdala, of both sexes, ranging in age from 21-805 days for male rats and from 21-780 days for the estrus and diestrus female rats, was measured. The oxidative activity of the hypothalamus, hippocampus, and amygdala decreased rapidly from Day 21 until the 4th mo. and stabilized till the 27th mo. in the hippocampus and amygdala and gradually decreased from the 12th mo. to the 27th mo. in the hypothalamus. The cerebral cortex showed a different pattern which kept a constant level from day 21 to 12 mo. of age. There was no statistically significant change in any of the regions at the time of vaginal opening. Low oxidative activity of the hypothalamus and amygdala in old age was still observed in castrated/hypophysectomized male rats compared with young ones. Therefore, the decreased oxygen consumption in old age seems to be due primarily to changes in the brain tissue itself and not due secondarily to changes in the gonadotropin and sex hormone levels. Female rats had higher oxygen consumption values than males in the cerebral cortex, the hypothalamus, and the hippocampus. In the amygdala the males had a higher consumption. Estrus female rats showed significantly higher oxygen consumption than diestrus females only in the hypothalamus.

Aging↗

Characteristics of endothelin receptors in the cerebral cortex and spinal cord of aged rats.

Characteristics of endothelin receptors were studied in male Fischer 344 rats at 4-, 15- and 24-months of age and [125I]ET-1 binding showed a single high affinity binding site in their cerebral cortex and spinal cord membranes. The density and affinity of ET binding sites were found to be similar in rats of various age groups. To determine the affinity of ET isotypes to ET-1 binding sites in cerebral cortex and spinal cord, competition studies were performed and K(i) values of ET-1, ET-2 and ET-3 for [125I] ET-1 binding sites were determined. It was found that ET-1 had 100 and ET-2 had 25-100 times lower K(i) values as compared to ET-3, indicating that ET receptors in cerebral cortex and spinal cord are of ETA type. In spinal cord, the K(i) values of ET-1 and ET-2 for ET receptor were found to be similar. However, in cerebral cortex the K(i) values of ET-1 were found to be at least 6 times lower than ET-2. It is inferred that there are two subtypes of ET(A) receptors, ET(A1) which have higher affinity for ET-1 in comparison to ET-2, as found in cerebral cortex and ET(A2) which have higher affinity for ET-2, as found in spinal cord. The K(i) and IC50 values of ET-1, ET-2, and ET-3 for [125I]ET-1 binding sites in cerebral cortex and spinal cord were found to be similar in 4-, 15- and 24-month-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation.

Cerebral cortex samples from patients with Alzheimer's disease and from rats after experimental cholinergic denervation of the cerebral cortex exhibited reductions in the presynaptic marker choline acetyltransferase activity and in the number of M2 muscarine receptors, with no change in the number of M1 receptors. These results are in keeping with evidence that M2 receptors function in cholinergic nerve terminals to regulate the release of acetylcholine, whereas M1 receptors are located on postsynaptic cells and facilitate cellular excitation. New M1-selective agonists and M2-selective antagonists directed at post- or presynaptic sites deserve consideration as potential agents for the treatment of the disease.

Aged↗

Localization of the motor and speech zones of the cerebral cortex by functional magnetic resonance tomography.

Functional magnetic resonance tomography provides a non-invasive method for mapping the cerebral cortex. The aim of the present work was to assess the potential and suitability of this method in a series of brain disorders. Studies were performed on 32 volunteers (mean age 37.8 +/- 20.9 years) and 16 patients with tumors of the cerebral cortex (mean age 36.2 +/- 24.2 years). Initial functional images were processed by statistical methods. Computed activation maps were superimposed on anatomical images. In 89% of cases, functional magnetic resonance tomography allowed the motor cortex and Broca's area to be localized; in almost 69%, the method impinged on the therapeutic tactics used in patients with cerebral cortex lesions. Thus, functional magnetic resonance tomography can be used in clinical conditions to obtain information not yielded by other diagnostic methods and which can be used to plan the neurosurgical treatment of patients with supratentorial brain tumors with maximum preservation of cerebral cortex function. Assessments of the state of the motor and speech areas by this tomographic method has potential applications in neurosurgery and neurophysiology.

Adolescent↗

Cholinergic enzyme activities and muscarinic binding in the cerebral cortex of rats of different age and sex.

1. The choline acetyltransferase and acetylcholinesterase activities in the cerebral cortex and hippocampus and muscarinic binding in the cerebral cortex did not differ significantly between male and female Wistar rats. 2. Choline acetyltransferase activities in the cerebral cortex and hippocampus of rats were not altered during ageing. 3. Acetylcholinesterase activities in these same brain areas were markedly decreased during ageing, possibly reflecting a loss of postsynaptic enzyme activity. 4. When measured using 3H-pirenzepine, binding to the postsynaptic muscarinic receptors was slightly higher in 26-month-old rats than in 12-month-old rats; total muscarinic binding measured using 3H-quinuclidinyl benzilate did not alter during ageing. 5. The present study does not support the hypothesis that in the rat brain the number of postsynaptic muscarinic binding sites decreases during ageing.

Aging↗

Characterization of Na+-independent GABA and flunitrazepam binding sites in preparations of synaptic membranes and postsynaptic densities isolated from canine cerebral cortex and cerebellum.

The binding of [3H]GABA and [3H]flunitrazepam was performed with synaptic membranes and post-synaptic densities (PSDs) isolated from canine cerebral cortex and cerebellum. Two GABA binding sites were found with cerebral cortex membranes but only one with cerebellar membranes. PSDs isolated from these showed only single binding sites, with cerebellar PSDs exhibiting lower KD values and a larger concentration of sites than did cerebral cortex PSDs. In the case of flunitrazepam, only one binding site was found for all four preparations, with cerebellar PSDs having twice the concentration of sites of cerebral PSDs. Photoaffinity labeling of the flunitrazepam receptor in PSDs resulted in the binding to a 51,000 Mr protein in both cases, with cerebellar PSDs again showing an increased concentration over that found in cerebral cortex PSDs. Based on this work, and on earlier work of ourselves and of others, we conclude that both populations of isolated PSDs contain inhibitory sites, but that the intact PSDs in both preparations are derived from Gray type I, probably excitatory, synapses, and that the inhibitory sites are found in the broken-up material in the PSD fractions which are derived from Gray type II, probably inhibitory, synapses.

Animals↗

Non-sprouting angiogenesis in neurohypophysis after traumatic injury of the cerebral cortex. Electron-microscopic studies.

OBJECTIVES: Angiogenesis comprises two different mechanisms: endothelial sprouting and intussusceptive microvascular growth. The sprouting process is based on endothelial cell migration, proliferation and tube formation. Intussusceptive microvascular growth divides existing vessel lumens by formation and insertion of endothelial columns into the vessel lumen. The morphological features of microvessels of cerebral cortex and neurohypophysis were evaluated in a model of the cerebral traumatic injury. METHOD: The observations were conducted seven days after induction of cortical trauma. Traumatic injury was induced in the fronto-temporal region of cerebral cortex in general anesthesia with 20mg/kg ketamine hydrochloride. RESULTS: Seven days after traumatic brain injury in sections from cerebral cortex and neurohypophysis we can observe morphological features of angiogenesis. Endothelium of the cerebral cortex possesses high endotheliocytes tightly connected and enveloped by amorphous basement membrane-like material. Transcapillary pillars tightly connected with neighbouring endothelial cells split the newly formed vessels and branching takes place. In neurohypophysis we can observe all stages of non-sprouting angiogenesis: proliferation endothelial cells on the inside mother vessel, splitting newly formed blood vessels by transcapillary pillars directed into the vessel lumen, maturation of endothelium and network formation. CONCLUSION: The mechanical injuries directly induced angiogenesis not only in cerebral cortex, but also in neurohypophysis. Our studies show that mechanism of angiogenesis is not the same as observed previously in neurohypophysis after focal cerebral ischemia (Neuroendocrinology Letters 2001; 22:87 92). This study indicates that mechanism of angiogenesis can depend on kind of induction.

Animals↗

Isolation and expression of an ischaemia-induced gene from gerbil cerebral cortex by subtractive hybridization.

A subtraction cDNA library was made using subtractive hybridization of cDNA libraries constructed from gerbil cerebral cortex of control animals and animals 8 h after 10 min of transient forebrain ischaemia. After differential screening, a cDNA clone (named pGSH3) was isolated as a gene which is expressed only after the ischaemia insult. The cDNA insert of pGSH3 (0.7 Kb) hybridized to 2.8 Kb mRNA of ischaemic cerebral cortex. The gene was normally expressed in a small amount in the cerebellum, kidney, and lung, but was not expressed in the cerebral cortex, heart, liver, or jejunum in a detectable amount. Eight hours after the 10-min transient forebrain ischaemia, the gene expression became prominent in the cerebral cortex, and the amount of the mRNA also increased in the lung and kidney. An analysis of DNA sequence revealed that the pGSH3 insert has a 91.3 per cent homology with a 70-Kd human heat shock protein (HSP70) gene. These results indicate that an ischaemia-induced gene was isolated as a cDNA clone (pGSH3) by subtractive hybridization and differential screening. Expression of the gene was first detected in other organs especially in the kidney and lung after transient forebrain ischaemia.

Animals↗

[Expression of androgen receptor gene in cerebral cortex and hippocampus of rats with perinatal hypothyroidism].

OBJECTIVE: To investigate the effects of perinatal thyroid hormone deficiency on the expression of androgen receptor (AR) mRNA in cerebral cortex and hippocampus of rats. METHODS: Perinatal hypothyroidism was induced by the administration of propylthiouracil (PTU) solution to the dams by gavage (50 mg/d) beginning at embryonic d15 throughout the lactational period. In the T(4) injected group hypothyroid rats were injected intraperitoneally with levothroxine (L-T(4)) 2 microg/100 g BW daily, starting from the day of birth. Cerebral cortex and hippocampus specimen were collected from controls,hypothyroid and T(4)-injected hypothyroid rats on postnatal d1, 5, 10, 15 and 20. Quantification of ARmRNA in cerebral cortex and hippocampus was performed with competitive RT-PCR using internal and external standardization. RESULT: Age-related increasing ARmRNA levels were observed in neonatal rats, and those in male animals were significantly higher. AR expression was higher in the hippocampus than in the cerebral cortex. ARmRNA levels in the hypothyroid pups were lower than those in age-matched controls. The mRNA levels in the T(4)-injected hypothyroid pups were significantly higher compared with the age-matched hypothyroid pups, but in hippocampus ARmRNA expression did not reach normal levels in male rats at d10 and d20, in female at d15 and d20. CONCLUSION: The expression of ARmRNA decreases in brain of rats with perinatal hypothyroidism. Treatment with thyroid hormone can recover ARmRNA expression in cerebral cortex, but not in hippocampus.

Animals↗

Changes in GABA and parvalbumin immunoreactivities in the cerebral cortex of lizards after narine occlusion.

Olfactory deprivation produced by narine occlusion has been suggested to reduce the activity in the cerebral cortex of lizards. Here we analyzed the short-term changes in GABA and parvalbumin (PV) immunoreactivities in the cerebral cortex of lizards after narine occlusion. The number and distribution of GABA- and parvalbumin-immunoreactive (IR) cells have been studied by immunocytochemistry in the cerebral cortex of control and olfactory-deprived lizards. The distribution of GABA-IR cells as well as that of PV-IR cells was similar in control and deprived animals, and PV-IR cells were GABA-IR in all cases. However, significant changes were observed in the absolute number of GABA- and PV-IR cells. GABA-IR cells were more abundant in deprived animals than in control ones. In contrast, the number of PV-IR cells decreased significantly and PV immunoreactivity in dendrites and boutons was lower in deprived animals. These results suggest that the reduction in the number of PV-IR cells in olfactory-deprived lizards occurs without loss of GABA cells, and that PV expression is under the control of olfactory activity and remains plastic in the cerebral cortex of adult lizards.

Animals↗

Relationship between age and GSH metabolism in synaptosomes of rat cerebral cortex.

A comprehensive analysis on glutathione metabolism in rat cerebral cortex synaptosomes as a function of age was performed. All different glutathione system components (GSH, GSSG, total GSH, and GSH redox index) changed significantly only during aging. GSH, total GSH, and GSH redox index decreased by about 40%, 24%, and 52%, respectively, while GSSG showed a remarkable increase of about 60%. On the contrary, some GSH-related enzyme activities showed characteristic changes both during growth and aging. GSH peroxidase and GSH-S-transferase activities significantly increased both during growth and aging, GSH reductase and gamma-glutamylcysteine synthetase activities showed lower levels only during aging, while glucose-6-phosphate dehydrogenase activity did not change throughout the life of the rat. The results obtained suggest an increase of the oxidative status due to a reduced antioxidant capacity of the GSH system in the synaptosomal compartment during aging. The main cause of these metabolic modifications is a lowering of the rates of both GSSG reduction to GSH and GSH synthesis. Moreover, an irreversible loss of GSH as GSH-S-conjugates due to a high detoxification mechanism during aging is also possible. These alterations in glutathione metabolism, found mainly during aging in rat cerebral cortex synaptosomes may contribute to clarify some aspects of cerebral diseases.

Aging↗

A simple new method for repeated in vivo cerebral cortex flux measurement in rats.

A new application of an indicator dilution technique, using nonradioactive para-aminohippuric acid, is described for superior sagittal sinus blood flow determination in rats. Superior sagittal sinus blood flow, mainly representing cerebral cortex blood flow, amounted to 541 +/- 49 microliters/min in ketamine-anesthetized, but otherwise normal, rats breathing room air. Increasing arterial pCO2 enhanced superior sagittal sinus blood flow (P less than 0.01), providing evidence that this method correctly measures cerebral blood flow. The respiratory quotient was 1.1 and the cerebral cortex metabolic rate of oxygen consumption was +/- 1.45 mumol/min. Cerebral cortex ammonia uptake was not significantly different from zero and of the amino acid fluxes, only alanine differed from zero (P less than 0.05). Flux measurements are crucial in studies of healthy or altered organ metabolism in both experimental animals and postoperative surgical patients. We devised a simple and economical method of repeated cerebral cortex flux measurement in rats that is a potentially valuable tool in metabolic studies of the cerebral cortex.

Animals↗