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PubMed1977

Ontogeny of beta-adrenergic receptors in rat cerebral cortex.

The ontogeny of beta-adrenergic receptors in rat cerebral cortex has been studied using [125I]iodohydroxybenzylpindolol as a ligand in an in vitro binding assay. The concentration of beta-adrenergic receptors was very low during the first week after birth. Between days 7 and 14 there was a rapid increase in the density of receptors. Adult levels were reached by the end of the second week. The affinities of 1-isoproterenol and iodohydroxybenzylpindolol for beta-adrenergic receptors did not vary with the age of the animal. Fluoride stimulated adenylate cyclase activity in the cerebral cortex was 40% of the adult level at birth and gradually increased to maximal levels over the next two weeks. On the other hand, catecholamine stimulated cyclic-3',5'-adenosine monophosphate accumulation was barely detectable during the first week after birth, but it increased rapidly to adult levels between days 7 and 14. The results suggest that it is the development of beta-adrenergic receptors that permits the expression of catecholamine sensitive adenylate cyclase activity. Norepinephrine stores in the cerebral cortex developed slowly reaching adult levels approximately two months after birth. There is therefore little correlation between the ontogeny of presynaptic adrenergic nerve terminals and the postsynaptic development of beta-adrenergic receptors.

Adenylyl Cyclases↗

PubMed1991

Metabolism and release of glutamate in cerebellar granule cells cocultured with astrocytes from cerebellum or cerebral cortex.

Cerebellar granule cells were cocultured with astrocytes from either cerebral cortex or cerebellum in two different systems. In one system the cells were plated next to each other only sharing the culture medium (separated cocultures) and in the other system the granule cells were plated on top of a preformed layer of astrocytes (sandwich cocultures). Using astrocytes from cerebellum, granule cells developed morphologically and functionally showing a characteristic high activity of the glutamate synthesizing enzyme aspartate aminotransferase (AAT) as well as a high stimulus-coupled transmitter release regardless of the culture system, i.e., granule cells could grow on top of cerebellar astrocytes as well as next to these cells. In the case of cerebral cortex astrocytes it was found that cerebellar granule cells did not develop (11% survival) when seeded on top of these astrocytes. This was indicated by the morphological appearance of the cultures as well as by a negligible difference between the AAT activity in sandwich cocultures and astrocytes cultured alone. On the other hand, granule cells in separated cocultures with cerebral cortex astrocytes exhibited a normal morphology and a high activity of AAT as well as a large stimulus-coupled transmitter release. Cerebellar and cortical astrocytes expressed the astrocyte specific enzyme glutamine synthetase in a glucocorticoid-inducible form regardless of the culture system. The results show that under conditions of direct contact between granule cells and astrocytes, regional specificity exists with regard to neuron-glia contacts. This specificity does not seem to involve soluble factors present in the culture medium because in separated cocultures the cerebellar granule cells developed normally regardless of the regional origin of the astrocytes.

Animals↗

PubMed2000

"Rodent-like" and "primate-like" types of astroglial architecture in the adult cerebral cortex of mammals: a comparative study.

Previous observations disclosed that astroglia with interlaminar processes were present in the cerebral cortex of adult New and Old World monkeys, but not in the rat, and scarcely in the prosimian Microcebus murinus. The present report is a more systematic and comprehensive comparative analysis of the occurrence of such processes in the cerebral cortex of several mammalian species. Brain samples were obtained from adult individuals from the following orders: Carnivora (canine), Rodentia (rat and mouse), Marsupialia (Macropus eugenii), Artiodactyl (bovine and ovine), Scandentia (Tupaia glis), Chiroptera (Cynopteris horsfieldii and C. brachyotis), and Primate: Prosimian (Eulemur fulvus), non-human primate species (Cebus apella, Saimiri boliviensis, Callithrix, Macaca mulatta, Papio hamadryas, Macaca fascicularis, Cercopithecus campbelli and C. ascanius) and from a human autopsy. Tissues were processed for immunocytochemistry using several antibodies directed against glial fibrillary acidic protein (GFAP), with or without additional procedures aimed at the retrieval of antigens and enhancement of their immunocytochemical expression. The cerebral cortex of non-primate species had an almost exclusive layout of stellate astrocytes, with only the occasional presence of long GFAP-IR processes in the dog that barely crossed the extent of lamina I, which in this species had comparatively increased thickness. Species of Insectivora and Chiroptera showed presence of astrocytes with long processes limited to the ventral basal cortex. Interlaminar GFAP-IR processes were absent in Eulemur fulvus, at variance with their limited presence and large within- and inter-individual variability as reported previously in Microcebus murinus. In New World monkeys such processes were absent in Callithrix samples, at variance with Cebus apella and Saimirí boliviensis. Overall, the expression of GFAP-IR interlaminar processes followed a progressive pattern: bulk of non-primate species (lack of interlaminar processes)--Chiroptera and Insectivora (processes restricted to allocortex) < strepsirhini < haplorhini (platirrhini < catarrhini). This trend is suggestive of the emergence of new evolutionary traits in the organization of the cerebral cortex, namely, the emergence of GFAP-IR long, interlaminar processes in the primate brain. Interlaminar processes may participate in a spatially restricted astroglial role, as compared to the one provided by the astroglial syncytium. It is proposed that the widely accepted concept of an exclusively astroglial syncytium is probably linked with a specific laboratory animal species ("rodent-type" or, rather, "general mammalian-type" model) that misrepresents the astroglial architecture present in the cerebral cortex of most anthropoid adult primates ("primate-type" model), including man.

Aged↗

PubMed1986

Epidermal growth factor in synaptosomal fractions of mouse cerebral cortex.

Using a specific and sensitive epidermal growth factor radioimmunoassay (EGF-RIA) we measured EGF concentrations in whole brain, cerebral cortex, and cerebral cortical synaptosomal (pinched-off presynaptic nerve terminals) fractions of 26-day-old mouse brain. The relative EGF concentration in synaptosomal fractions was significantly greater than the growth factor concentrations in whole brain or cerebral cortex. Intracerebral injection, in an amount of EGF, several-fold greater than whole brain EGF content, did not appreciably increase synaptosomal EGF concentration, suggesting that no artifact was involved. The high synaptosomal EGF content suggests a neurotransmitter or a neuromodulator role for EGF in the CNS.

Animals↗

PubMed1988

Immunocytochemical localization of somatostatin in the cerebral cortex of lizards.

The distribution of somatostatin-like immunoreactivity in the cerebral cortex of two lizards has been studied. Results are similar in both species. Somatostatin-positive neurons show variable morphology; they are bipolar, multipolar or pyramidal cells. Their distribution within the cerebral cortex is not homogeneous: they tend to be found in the innermost cortical layer, the deep plexiform layer, where they constitute a constant population in the region of the dorsomedial cortex. All immunoreactive processes observed in the cerebral cortex belong to somatostatin cortical neurons since no immunoreactive fiber is found to reach or leave the telencephalic cortex. Most of the dendrites are smooth or sparsely spinous. Axons are abundant in the deep plexiform layer; in the dorsomedial cortex a prominent terminal field appears in the outermost region of the superficial plexiform layer, which may arise from the neuronal somatostatin immunoreactive population found deeper in the same cortex.

Animals↗

PubMed1983

Binding properties of alpha-1 adrenergic receptors in rat cerebral cortex: similarity to smooth muscle.

The characteristics of alpha-1 adrenergic receptors in rat cerebral cortex were examined using the radioiodinated alpha-1 adrenergic receptor antagonist [125I]BE 2254 [( 125I]BE). [125I]BE labeled a single class of high-affinity binding sites in a particulate fraction of rat cerebral cortex with mass action kinetics and a KD of 57 pM. The binding of [125I]BE was inhibited by various alpha adrenergic receptor antagonists, partial agonists and full agonists. The potency of these compounds in competing for the [125I]BE binding sites suggested that [125I]BE was labeling alpha-1 adrenergic receptors in rat cerebral cortex. In the absence of a physiological concentration of NaCl in the assay medium there was a small (20%) decrease in the density of [125I]BE binding sites with no effect on the KD value. The absence of NaCl also caused a 4-fold increase in the potency of norepinephrine in competing for [125I]BE binding sites. All drugs competed for [125I] BE binding sites with Hill coefficients greater than 0.86, except for oxymetazoline which had a Hill coefficient of 0.77. Scatchard analysis of specific [125I]BE binding in the presence of various competing drugs showed that the inhibition by both agonists and antagonists was purely competitive, but the inhibition by oxymetazoline was complex. Treatment of the particulate fraction of rat cerebral cortex with 0.2 to 200 nM phenoxybenzamine for 10 min caused a dose-dependent decrease in the density of [125I] BE binding sites which could be mostly blocked by the presence of norepinephrine during the phenoxybenzamine exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1992

Messenger RNAs coding for receptors and channels in the cerebral cortex of adult and aged rats.

Poly(A)+ mRNAs from the cerebral cortex of aged (24 months) and young adult (3 months) rats were isolated and injected into Xenopus oocytes to express functional neurotransmitter receptors and voltage-operated channels. Electrophysiological recordings of induced membrane currents were used as a measure of the relative amounts of mRNA encoding different receptors and channels, and to study their functional properties. There were no large differences apparent between mRNAs from aged and adult rats, in marked contrast to the dramatic (1000-fold) changes in mRNA expression that occur during embryonic and postnatal development. The membrane currents induced by glutamate or acetylcholine (ACh) application were roughly one third smaller in oocytes injected with mRNA from aged cerebral cortex than in oocytes injected with mRNA from adult cerebral cortex, whereas currents induced by gamma-aminobutyric acid (GABA), kainate or serotonin (5-HT) application, and by activation of voltage-operated Na+ and Ca2+ channels were not significantly different. We did not observe any age-related differences in the properties of the receptors and channels studied.

Acetylcholine↗

PubMed2002

Comparative study of the epileptogenic effect of kainic acid injected into the cerebral cortex, hippocampus and amygdala in adult cats chronically implanted.

Intracerebral injection of kainic acid in cerebral cortex, hippocampus or amygdala in cats chronically implanted showed that: 1) Hippocampus and amygdala presented a greater sensitivity than the cerebral cortex, while hippocampus presented a greater sensitivity than the amygdala to the generation of an epileptic focus. 2) Comparison of latency, mean duration of afterdischarges, and the mean time period to obtain the peak intensity of the afterdischarge in the three cited structures, showed that mean latency of the first afterdischarge was significantly shorter in hippocampus and amygdala compared with the cerebral cortex. Moreover the mean time period to reach the peak intensity of the afterdischarge was again shorter in the subcortical structures. 3) The epileptic foci both in hippocampus and amygdala were blocked by CNQX and muscimol. 4) The behavioral changes depended on the intensity of the epileptic process. Tonic-clonic convulsions appeared only when the motor cerebral cortex was involved. Finally, 5) kainic acid injections in hippocampus and amygdala elicited an intense neuronal destruction and gliosis of these structures. We conclude that intracerebral injection of low doses of kainic acid in cats represent a good model to study focal epileptic thresholds in the CNS.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1992

Co-localization of hyaluronic acid and chondroitin sulfate proteoglycan in rat cerebral cortex.

The distribution of hyaluronate (HA) and chondroitin sulfate (CS) proteoglycan in the rat cerebral cortex was compared. For the localization of HA, the sections were incubated with human glial hyaluronate-binding protein (GHAP) and then reacted with monoclonal or polyclonal antibodies to GHAP. Polyclonal antibodies raised in rabbit were used for double-labeling experiments with monoclonal antibodies raised in mice and reacting with CS proteoglycans. Little reactivity was observed in rat cerebral cortex with polyclonal GHAP antibodies if the sections were not incubated with GHAP. Monoclonal antibodies to GHAP did not react with murine tissues. CS proteoglycans were localized in chondroitinase-digested sections with monoclonal antibodies reacting with the 4-sulfated oligosaccharide stubs formed by the digestion with chondroitinase ABC of CS side chains. In the rat cerebral cortex, the distribution of CS proteoglycans was similar to that reported by Bertolotto, A., Rocca, G. and Schiffer, D., J. Neurol. Sci., 100 (1990) 113-123, and his collaborators using the same antibodies. Many neurons mainly located in the upper and deep cortical layers were surrounded by CS immunoreactive material. Several (but not all) CS-positive neurons also stained for HA with an identical distribution except that in most instances the staining was confined to the periphery of the perikaryon and did not extend to the dendritic tree. The finding suggests that cerebral cortex CS proteoglycan is capable of interacting with HA.

Animals↗

PubMed2004

Interlaminar astroglia of the cerebral cortex: a marker of the primate brain.

Evidence for "cable-like" processes stemming from astroglial cells in the supragranular cerebral cortex has been recently presented. In addition to what could be called the "general mammalian-like" astroglial architecture (the so-called "panglial syncytium") of the cerebral cortex, composed of typical stellate astrocytes (intralaminar astrocytes), the anthropoid species, mostly catarrhines, show a manifest vertical, radial distribution of long (interlaminar) astroglial processes. It can be tentatively proposed that evolutionary pressures resulted in the progressive appearance, in primates, of a new type of glial cell. Its soma has a superficial location and unusually long cellular processes that invade, in a predominant radial fashion, the supragranular region of the cerebral cortex. Their existence has been ignored for more than a century. On the neuronal side, modular (columnar) organization of the cerebral cortex may represent an evolutionary acquisition that could optimize communication and information processing, with the least volume compromise in terms of wiring. Yet, for such columns to be functionally operative, adequate isolation from neighboring units would be required. A "mass" operation of the astroglial architecture would tend to compromise spatial definition and the degrees of freedom of such columnar modules. It is proposed that the presence of a "palisade" of interlaminar glial processes represents a relatively recent evolutionary event, instrumental for the optimization of the modular (columnar) organization of the cerebral cortex. It is interesting that the supragranular cortical region has undergone the largest growth among mammalian species during brain evolution, and has been associated with a crucial role in cortico-cortical interactions.

Animals↗

PubMed1988

Immunohistochemical study of glutaminase-containing neurons in the cerebral cortex and thalamus of the rat.

In an attempt to identify glutamatergic neurons, the cerebral cortex and thalamus of the rat were examined immunohistochemically by using a monoclonal antibody against phosphate-activated glutaminase (PAG), a major synthetic enzyme of transmitter glutamate in the central nervous system. In both the neocortex and mesocortex, pyramidal cells in layers V and VI showed intense PAG-like immunoreactivity (PAG-LI), whereas neuronal cell bodies in layers I-IV showed weak PAG-LI. At the deep border of layer VI, neurons with horizontally elongated cell bodies showed PAG-LI. In the pyriform and entorhinal cortices, neurons with intense to moderate PAG-LI were seen in layer II as well as in the deeper layers. In the hippocampal formation, pyramidal cells in CA1, CA2, and CA3 and polymorphic cells in CA4 showed PAG-LI; PAG-LI was most intense in pyramidal cells of CA3. Fine granules with weak PAG-LI were also seen on and/or within the cell bodies of granule cells in the dentate gyrus. In the thalamus, neurons with PAG-LI were distributed in all nuclei, although regional differences were observed in the distribution pattern of neurons with PAG-LI and in the intensity of PAG-LI in individual neurons. The largest neurons in each thalamic nucleus showed intense PAG-LI; these were considered to be projection neurons. In addition to perikaryal labeling, many fine, PAG-like immunoreactive granules were distributed in the neuropil of both the cerebral cortex and thalamic nuclei. Some of these fine granules with PAG-LI in the neuropil were assumed to represent fiber terminals with PAG-LI, because the distribution pattern of the deposits in the primary somatosensory and primary visual cortices resembled that of thalamocortical fiber terminals. Glutamate is rather ubiquitous in the mammalian central nervous system, and it is still debatable whether the monoclonal antibody to PAG from brain mitochondria can distinguish transmitter-related glutaminase from the other metabolism-related ones. In the present study, however, large neurons in the thalamic nuclei, as well as pyramidal neurons in the cerebral cortex, showed PAG-LI most intensely, supporting the assumption that projection neurons of the cerebral cortex and thalamus are primarily glutamatergic.

Animals↗

PubMed1987

Binding of [3H]Ro 5-4864 and [3H]PK 11195 to cerebral cortex and peripheral tissues of various species: species differences and heterogeneity in peripheral benzodiazepine binding sites.

The binding of [3H]PK 11195 and [3H]Ro 5-4864 to membrane preparations from cerebral cortex and peripheral tissues of various species was studied. [3H]PK 11195 (0.05-10 nM) bound with high affinity to rat and calf cerebral cortical and kidney membranes. [3H]Ro 5-4864 (0.05-30 nM) also successfully labeled rat cerebral cortical and kidney membranes, but in calf cerebral cortical and kidney membranes, its binding capacity was only 3 and 4%, respectively, of that of [3H]PK 11195. Displacement studies showed that unlabeled Ro 5-4864, diazepam, and flunitrazepam were much more potent in displacing [3H]PK 11195 from rat cerebral cortex and kidney membranes than from calf tissues. The potency of unlabeled Ro 5-4864 in displacing [3H]PK 11195 from the cerebral cortex of various other species was also tested, and the rank order of potency was rat = guinea pig greater than cat = dog greater than rabbit greater than calf. Analysis of these displacement curves revealed that Ro 5-4864 bound to two populations of binding sites from rat and calf kidney and from rat, guinea pig, rabbit, and calf cerebral cortex but to a single population of binding sites from cat and dog cerebral cortex. Using [3H]PK 11195 as a ligand, the rank order of binding capacity in cerebral cortex of various species was cat greater than calf greater than guinea pig greater than rabbit greater than dog greater than rat, whereas when [3H]Ro 5-4864 was used, the rank order of binding capacity was cat greater than guinea pig greater than rat greater than rabbit greater than calf greater than dog.

Animals↗

PubMed1996

Early and transient increase in oxidative stress in the cerebral cortex of senescence-accelerated mouse.

Age-related changes in oxidative stress in the cerebral cortex of SAMP8, a substrain of senescence-accelerated mouse (SAM), were investigated in comparison with those in SAMR1, which were used as a control. The lipid peroxide and protein carbonyl contents were transiently increased in SAMP8 from 4- to 8-weeks of age. The increases in lipid peroxide were seen only in the cerebral cortex and not in other regions of the cerebrum. Furthermore, the net generation of reactive oxygen species in cerebral cells was also increased in SAMP8. In addition, the activity of glutamine synthetase, which is known as an enzyme-highly sensitive to reactive oxygen, was decreased in the cerebral cortex of SAMP8 from 4- to 8-weeks of age. These results suggest that oxidative stress may be induced in the cerebral cortex of SAMP8 from 4- to 8-weeks of age, preceding the appearance of distinctive deficits in the brain of SAMP8.

Aging↗

PubMed2003

Degeneration of tyrosine hydroxylase-immunoreactive neurons in the cerebral cortex and hippocampus of patients with dementia with Lewy bodies.

We immunohistochemically investigated the degeneration of tyrosine hydroxylase (TH)-positive neurons in the cerebral cortex and hippocampus of dementia with Lewy bodies (DLB) brains. TH-positive neurons in the cerebral cortex and hippocampus were decreased in number, and were rarely associated with Lewy bodies (LB) or neurofibrillary tangles (NFT). A mild to moderate loss of TH-positive neurons was observed in both the cerebral cortex and substantia nigra. In addition, most brains showing low NFT stages and lacking amyloid deposits (AM), corresponding to pure-form DLB brains, demonstrated a moderate to severe loss of TH-positive neurons. These findings suggest that TH-positive neurons in the cerebral cortex degenerate by a pathomechanism similar to that in the substantia nigra, and that the degeneration of these neurons is partly related to LB or NFT formation in either the substantia nigra or cerebral cortex.

Aged↗

PubMed1987

Effects of nucleus basalis lesions on the muscarinic and nicotinic modulation of [3H]acetylcholine release in the rat cerebral cortex.

Presynaptic muscarinic and nicotinic receptors in the cerebral cortex reportedly inhibit and increase acetylcholine (ACh) release, respectively. In this study, we investigated whether these receptors reside on cholinergic nerve terminals projecting to the cerebral cortex from the nucleus basalis magnocellularis (nbm). Adult male rats received unilateral infusions of ibotenic acid (5 micrograms/1 microliter) in the nbm. Two weeks later, cerebral cortical cholinergic markers (choline acetyltransferase activity, high-affinity choline uptake, and coupled ACh synthesis) were significantly reduced in synaptosomes prepared from the lesioned hemispheres compared to contralateral controls. The depolarization-induced release of [3H]ACh from these synaptosomes was also reduced in the lesioned hemispheres, reflecting the reduced synthesis of transmitter. However, the nbm lesions had no effect on the inhibition of release induced by 100 microM oxotremorine. Synaptosomal [3H]ACh release was not altered by nicotine or the nicotinic agonists anabaseine and 2-(3-pyridyl)-1,4,5,6-tetrahydropyrimidine. Nicotine (10-100 microM) did increase [3H]ACh release in control and lesioned hemispheres in cortical minces, but to a similar extent. These results suggest that neither muscarinic nor nicotinic receptors modulating ACh release reside on nbm-cholinergic terminals.

Acetylcholine↗

PubMed1999

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB.

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Culture and identification of monoclonal neural stem cells derived from cerebral cortex.

To isolate and culture the purified monoclonal neural stem cells from the cerebral cortex of new born mice, new-born mice cerebral cortex was isolated and dissociated to single-cell suspension by mechanical trituration. The dissociated single cells were cultured in serum-free medium. After the formation of neurospheres, single-cell clone culture was performed by limiting dilution and the proliferated single-cell clones were harvested for subculture. Immunocytochemistry was used to detect the specific marker of neuroepithelial stem cells (Nestin) of the primary and monoclonal neurospheres. In the differentiated cells we detected the specific antigen of NF-200 and GFAP. Our results showed that the primary neurospheres expressed Nestin antigen positively. By limiting dilution, we cultured the cell lines from single-cell clone and the monoclonal neurospheres expressed Nestin and had capabilities of self-renewal, proliferation and the potentiality of differentiation into neurons and glial cells. It is concluded that monoclonal neural stem cells which have the ability of proliferation and multi-directional differentiation can be isolated and cultured from the cerebral cortex of new-born mice by limiting dilution.

Animals↗

PubMed2003

Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma.

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor-infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress-related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor-infiltrated cortex and apparently non-infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP-2, neurofilament proteins), beta-amyloid precursor protein, growth associated protein-43 and to injury response proteins (poly(ADP-ribose) polymerase, poly(ADP-ribose), c-fos, and c-jun). Tumor-infiltrated cortex revealed neuronal loss and architectural disarray compared to non-infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP-ribose) polymerase, poly(ADP-ribose) and c-fos were up-regulated in both infiltrated and non-infiltrated cortex, but c-jun expression was greater in areas of tumor-infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.

Astrocytoma↗