Structural changes in cerebral cortex during cobalt-induced epilepsy in the rat

Rods of cobalt metal were inserted into rat cerebral cortex to produce experimental epilepsy. Brain sections were then stained and examined for structural changes at several survival times. Times were based on previous electrocorticographic studies. Comparisons were made with tissue from rats implanted with non-epileptogenic copper or glass rods. Gliosis was much more extensive after copper than after cobalt. Silver-staining revealed unusual , dark granules associated with neurons only in the cobalt-treated rats. Three weeks after cobalt treatment, enlarged perikarya were observed around the implant. The possible significance of these findings is discussed.     

NADPH-diaphorase histochemistry in the rat cerebral cortex and hippocampus: effect of electrolytic lesions of the nucleus basalis magnocellularis

Unilateral or bilateral electrolytic lesions of the nucleus basalis magnocellularis (NBM) increased NADPH-diaphorase in the fronto-parietal cortex and in the CA1-CA3 fields of the hippocampus. NBM is the cholinergic basal forebrain nucleus supplying the fronto-parietal cortex but not the hippocampus. This increase was more remarkable at 4 weeks than at 2 weeks after lesioning. Monolateral or bilateral lesioning of the NBM increased to a similar extent NADPH-diaphorase. The number of neurons expressing NADPH-diaphorase was not statistically different between sham-operated and NBM-lesioned rats. These results indicate that similarly as reported in experimental damage of several brain areas, lesions of the NBM induce NADPH-diaphorase. The induction of this marker for nitric oxide synthase occurs both in the target of projections arising from the NBM such as the frontal cortex and in an area not directly supplied by NBM such as the hippocampus. Lesion-induced NADPH-diaphorase increase may contribute to neurodegenerative changes caused by damage of the NBM area.     

Developmental changes of glutamate receptors in the rat cerebral cortex and hippocampus

We studied the immunohistochemial localization of the glutamate receptors (GluR-1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3) subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons from postnatal day (PND) 0, increased with maturation, was highest at PND?10, decreased until PND 30, and thereafter remained at the same level as on PND?0. GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day (ED) 18, increased with maturation and reached a peak between PND?10 and PND?15, after which the immunoreactivity gradually decreased and reached a plateau at PND?30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in all the pyramidal neurons of the CA1–4 area from ED?20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in the neurons of the granule cells after PND?0. Immunoreactivity in the neurons of the subiculum was found after PND?5 and that of the polymorphic cell layers was found after PND?15–20. Our results indicate that the development of glutamate receptor subunits in the rat cerebral cortex and hippocampus is expressed in different spatial patterns and distinct temporal patterns throughout development and is scheduled during the early postnatal period, when synaptic plasticity or synaptic connection occurs in these regions.     

Developmental changes of glutamate receptors in the rat cerebral cortex and hippocampus

 We studied the immunohistochemial localization of the glutamate receptors (GluR-1, -2, and -3,) in the developing rat cerebral cortex and hippocampus using antibodies to GluR1 and to an epitope common to GluR2 and GluR3 (GluR2/3) subunits. In the cerebral cortex, GluR1 immunoreactivity appeared in the neurons from postnatal day (PND) 0, increased with maturation, was highest at PND 10, decreased until PND 30, and thereafter remained at the same level as on PND 0. GluR2/3 immunoreactivity appeared earlier in scattered neurons on embryonal day (ED) 18, increased with maturation and reached a peak between PND 10 and PND 15, after which the immunoreactivity gradually decreased and reached a plateau at PND 30. For both GluR1 and GluR2/3, some of the pyramidal neurons showed intense staining. In the pyramidal layers of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in all the pyramidal neurons of the CA1–4 area from ED 20. In the dentate gyrus of the hippocampus, GluR1 and GluR2/3 immunoreactivity was found in the neurons of the granule cells after PND 0. Immunoreactivity in the neurons of the subiculum was found after PND 5 and that of the polymorphic cell layers was found after PND 15–20. Our results indicate that the development of glutamate receptor subunits in the rat cerebral cortex and hippocampus is expressed in different spatial patterns and distinct temporal patterns throughout development and is scheduled during the early postnatal period, when synaptic plasticity or synaptic connection occurs in these regions. Accepted: 13 June 1996     

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     

Developmental pattern of NADPH-diaphorase activity and nitric oxide-stimulated cGMP immunoreactivity in the frontal rat cortex and its role in functional recovery from aspiration lesions

The present study was undertaken to (1) explore the cortical nitric oxide (NO)-system during postnatal development and (2) to see whether or not the NO-system reacts differentially after neonatal and adult lesions of the medial prefrontal cortex. Three aspects of the NO-system were studied, i.e., NADPH-diaphorase (NADPH-d) activity, sodium nitroprusside (SNP)- and N-methyl- -aspartate (NMDA)-stimulated cGMP-immunoreactivity (cGMP-IR). It was shown that: (1) the development of NADPH-d activity containing cells is continued in the period from P6 until P21; (2) during the same period, large developmental changes take place in basal, and SNP- or NMDA-stimulated cGMP-IR in the cortex. These changes are regionally specific and follow the general cortical developmental pattern; and (3) aspiration lesions do not induce major changes in the distribution of NADPH-d activity or cGMP-IR, either basal, SNP- or NMDA-stimulated.     

Structural and biochemical changes in rat cerebral cortex after neonatal 6-hydroxydopamine administration

Summary Newborn rats received an intracisternal injection of 6-hydroxydopamine (100 g) within 16 h after birth. Treatment effects upon noradrenaline uptake (with or without desmethylimipramine pre-incubation), endogenous noradrenaline, dopamine, and serotonin were biochemically assayed. Noradrenaline uptake and endogenous noradrenaline content were permanently reduced to less than 5% of control values. Reduction of endogenous dopamine content was less marked: at day 60, values were about 40% of controls. Serotonin content remained unaffected.Cell density countings in postnatal day 15 temporal cortex revealed an about 16% reduction in layers II and III of treated animals. These modifications of cortical geometry were discussed with reference to measurements of cortical thickness and ultrastructural observations on postnatal days 2, 5 and 15. Both supranormal involution and growth processes might result from the neurotoxin treatment. Whereas some of the degeneration processes might be due to general cytotoxic effects, this is less likely for the supranormal growth processes.     

Studies on the vasculogenesis in rat cerebral cortex

The cerebral cortices are nourished by blood circulating through a capillary network branching from parent arteries. In this paper, vasculogenesis of the cerebral cortices in developing rats (11-18 days after birth) was studied by light and electron microscopy after intravenous administration of horseradish peroxidase (HRP). In the first phase of vasculogenesis, tentacles grew out from the distal end of the vascular cord (tip cells), and in the second phase, they extended to the afferent blood vessel. The reaction product of HRP was distributed not only in the primitive vascular lumen, but also in the peripheral extravascular space of the vascular cord. Most tentacles were free from reaction product, but, in some cases where reaction product was detected, the intercellular spaces had spread into the tip cells and reached the root of the tentacles. After the tentacles contacted the afferent vascular cord, the two vascular cords approached and fused with each other. Blood serum was able to circulate between the two vascular cords via the irregular interstices formed among the endothelial cells, cytoplasmic processes, and tentacles. Later, the primitive vascular lumen developed to a sufficient size to allow for the circulation of blood cells. The sequential events in the process of fusion between two vascular cords are illustrated. The following two points were also noticed in this study: 1) during cerebral vasculogenesis, degeneration and vacuolization in primitive endothelial cells occurred only in some of the serial sections and did not play a significant role in the formation of vascular lumen, and 2) cerebral pericytal macrophages (CPM) (classified as fluorescent granular perithelial cells by the authors) appeared close to the vascular cord, although the biological meaning of it remained unknown in the present investigation.     

Sensory interactive zones in the rat cerebral cortex

The acoustic, somatosensory and visual areas of the rat cerebral cortex were mapped in view of overlapping regions, giving polysensory evoked responses. In case of each pair of modalities overlapping areas were found between the cortical representations. The evoked potentials of two different modalities show occlusive and facilitatory interactions in these overlapping areas. In the "core" region of these areas, points with especially high values of occlusion are concentrated while at the periphery weak occlusion or even facilitation is characteristic. It is supposed that the polysensory areas interposed between primary sensory fields represent not only areas with mixed responsiveness but also stage for real physiological interactions between different sensory systems.     

Perineuronal germinal cells in the rat cerebral cortex

The generation and renewal of cells in the adult mammalian central nervous system maintains brain functions, including plasticity. Even in the cerebral cortex of adult mammals, glial cells are thought to be replaced with newly generated cells every 100 days. Recently, we demonstrated that this proliferation is stimulated by neural activity. However, whether any germinal areas exist in the cortical parenchyma is unknown. Here, we examined the proliferating cell dynamics in the cerebral cortex of adult rats using BrdU labeling and immunohistochemistry for NeuN and lamin B1. At 2 h after a single injection of BrdU, more than 80% of BrdU-labeled cells were observed in the perineuronal territory in which the BrdU-labeled nuclei were located within 5 μm from neuronal nuclei. The ratio of perineuronal cells to nonperineuronal cells in BrdU-labeled cells gradually decreased over the 2 weeks following BrdU injection. These observations indicate that numerous cortical cells proliferate in the perineuronal territory, the germinal soil, and that part of these newly generated cells migrate from the perineuronal territory into the surrounding areas during the 2 weeks following mitosis.     

Access to the cerebral cortex of extra-lingual taste inputs in the rat

Rats with their intra-lingual taste nerves (the chorda tympani and the glossopharyngeal nerve) sectioned were trained to avoid drinking 0.5 M NaCl solution by associating NaCl drinking with subsequent LiCl poisoning. The acquired learned aversion in these rats was abolished after ablations of the neocortical area for the intra-lingual taste nerves. This result indicates that extra-lingual taste inputs from the palatine and epiglottal taste buds share the neocortical taste area with intra-lingual taste inputs.     

Cholinergic mechanisms in the rat somatosensory cerebral cortex

1. The responses of identified cells in the rat cerebral cortex to cholinomimetic and anticholinergic substances has been investigated.2. Acetylcholine and muscarinic agonists have an excitatory action on 80% of pyramidal tract cells. This response is found especially on cells responding to specific thalamic stimulation and the burst of spikes evoked from this site can sometimes be blocked by the iontophoresis of atropine. This strongly suggests an excitatory transmitter function for acetylcholine in a specific thalamocortical pathway.3. Experiments on non-pyramidal tract cells have detected a muscarinic depression of some cells, and a nicotinic excitation of some cells above a depth of 600 mu in the cortex.4. It is suggested that the increased release of acetylcholine from the cortex produced by atropine administration may be due to an excess of muscarinic inhibitory over excitatory synapses in the cortex.     

Ultrastructural changes in the cerebral cortex after transcranial micropolarization

An electron-microscopic investigation of the cerebral cortex of cats and monkeys after transcranial micropolarization (TCMP) revealed ultrastructural changes the severity of which depended on the intensity of the current and the duration of its action. In the focus of exposure the current acted directly on the brain tissue, but the cerebral cortical cells differed in their sensitivity to different conditions of TCMP. The most reactive tissue was the glia, followed by the bodies of neurons and synaptic structures. In areas of brain remote from the focus of TCMP the ultrastructural organization of the synapses was principally altered. The morphological changes discovered were not pathological.Laboratory of Physiological Mechanisms of Memory Control, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR N. P. Bekhtereva.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 737–739, December, 1978.     

Morphological changes in the cerebral cortex after a stroke

29 brains of right-handed persons who died within the period of 4 hours to 6 years after the stroke were studies. The patients had various disorders of speech and movements, partial or complete speech recovery was observed in 10 cases. Aphasias resulted from the lesions of associative fibers connecting the speech zones of the brain cortex, direct destruction of speech regions, in cases of hematoma pressure on cortex speech areas. Changes in neurons, nerve fibres and neuroglia in the cortex of speech areas were determined by the time passed after the stroke. They were also dependent on the site and size of the focus and, to a certain extent, correlated with a clinical picture. The changes also depended on localization and the size of lesion. Sometimes the changes correlated with clinical data. Clinical and morphological comparisons indicate that a correlation exists between speech recovery degree and the intensity of repairing processes in neurons and nerve fibres in cortical speech areas.     

Age-related changes in mitochondrial respiration and oxidative damage in the cerebral cortex of the Fischer 344 rat

This study probed possible age-related changes in mitochondrial bioenergetics in naïve Fischer 344 rats. Synaptic and extrasynaptic mitochondria were isolated from the cortex of one hemisphere of young (3-5 months), middle (12-14 months), or aged (22-24 months) rats. Respiration parameters were obtained using a Clarke-type electrode. Aged rats displayed no significant alterations in respiration, indicating mitochondria must be more resilient to the aging process than previously thought. Synaptic mitochondria displayed lower respiration capacities than the extrasynaptic fraction. Aged F344 rats appear capable of normal electron transport chain function without declines in ability to produce ATP. Markers of cortical oxidative damage (3-nitrotyrosine [3-NT], 4-hydroxynonenal [4-HNE], and protein carbonyls [PC]) were collected from the post-mitochondrial supernatant (PMS) from the contralateral hemisphere, and from mitochondrial samples following respiration analysis. Age-related increases in PC and 3-NT levels were found in synaptic mitochondria, whereas significant extrasynaptic elevations were only found in middle aged rats. These findings support an age-related increase in oxidative damage in the cortex, while proposing the two fractions of mitochondria are differentially affected by the aging process. Levels of oxidative damage that accumulates in the cortex with age does not appear to significantly impair cortical mitochondrial respiration of F344 rats.     

Morphological changes of c-Fos-like immunoreactivity in rat cerebral cortex after cerebral ischemia and reperfusion with special reference to vasoactive intestinal polypeptide

We investigated morphological changes in neurons with c-Fos-like immunoreactivity (c-Fos-LI) after cerebral ischemia by light and electron microscopic immunocytochemistry. Strong c-Fos-LI was observed in layers II–VI of the cerebral cortex with an especially abundant distribution in the nuclei of layers II, IV, and VI ipsilateral to the lesioned side. Reperfusion after ischemia had a greater effect on the expression of c-Fos-LI than did permanent ischemia. Vasoactive intestinal peptide (VIP)-positive neurons were seen scattered in layers II–V of the cerebral cortex. Some VIP-positive neurons showed c-Fos-LI after ischemia. Electron microscopy revealed c-Fos-LI in euchromatin in the nuclei of c-Fos-positive cells. Dilatation of the cisternae of the rough endoplasmic reticulum and the presence of numerous secondary lysosomes were found in neurons on the lesioned side after 12h of reperfusion. Some VIP-containing neurons revealed c-Fos-LI with reperfusion after ischemia by a double immunostaining method on the same tissue section. These findings suggest that ischemia potentiates c-fos expression in VIP- or other transmitter- or modulator-containing neurons, thereby protecting from neuronal cell death.