Axonal and nonneuronal cell responses to spinal cord injury in mice lacking glial fibrillary acidic protein

We have examined the regeneration of corticospinal tract fibers and expression of various extracellular matrix (ECM) molecules and intermediate filaments [vimentin and glial fibrillary acidic protein (GFAP)] after dorsal hemisection of the spinal cord of adult GFAP-null and wild-type littermate control mice. The expression of these molecules was also examined in the uninjured spinal cord. There was no increase in axon sprouting or long distance regeneration in GFAP-/- mice compared to the wild type. In the uninjured spinal cord (i) GFAP was expressed in the wild type but not the mutant mice, while vimentin was expressed in astrocytes in the white matter of both types of mice; (ii) laminin and fibronectin immunoreactivity was localized to blood vessels and meninges; (iii) tenascin and chondroitin sulfate proteoglycan (CSPG) labeling was detected in astrocytes and the nodes of Ranvier in the white matter; and (iv) in addition, CSPG labeling which was generally less intense in the gray matter of mutant mice. Ten days after hemisection there was a large increase in vimentin+ cells at the lesion site in both groups of mice. These include astrocytes as well as meningeal cells that migrate into the wound. The center of these lesions was filled by laminin+/fibronectin+ cells. Discrete strands of tenascin-like immunoreactivity were seen in the core of the lesion and lining its walls. Marked increases in CSPG labeling was observed in the CNS parenchyma on either side of the lesion. These results indicate that the absence of GFAP in reactive astrocytes does not alter axonal sprouting or regeneration. In addition, except for CSPG, the expression of various ECM molecules appears unaltered in GFAP-/- mice.     

Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats

The endogenous expression of basic fibroblast growth factor (bFGF) was blocked by neutralizing antibodies following unilateral suction lesions of the motor cortex. Rats with control treatment (saline, goat IgG) after motor cortex lesions showed slow recovery of forelimb manipulatory abilities. Rats with blockade of bFGF expression showed little recovery. Anatomically, the control-treated lesioned rats showed an acute increase in bFGF and glial fibrillary acidic protein (GFAP) reactivity, and chronically they had normal dendritic arborization and spine density in layer V pyramidal cells in the remaining motor cortex. In contrast, rats treated with antibodies to bFGF showed little bFGF reactivity, normal GFAP reactivity, and atrophy of dendritic arbor and decreased spine density in layer V pyramidal cells. These results demonstrate the importance of endogenous bFGF release in processes related to functional recovery after cortical injury.     

Glial fibrillary acidic protein expression but no glial demarcation follows the lesion in the molecular layer of cerebellum

The present study investigates the reactive gliosis following a simple stab wound lesion to a brain area in which a characteristic astroglial architecture exists, i.e., the Bergmann-glia in the molecular layer of cerebellum. While in mammalian brain the Bergmann-glia contains glial fibrillary acidic protein (GFAP), in the avian Bergmann-glia, the cytoskeletal protein is vimentin, which is characteristic for immature astroglia in mammals. The operations were performed on chickens and rats under deep anaesthesia, using a sterile disposable needle. After a 1-week survival period, the animals were overdosed with ether and perfused transcardially with 4% buffered paraformaldehyde. Free-floating sections cut with a vibration microtome were processed for immunohistochemistry against GFAP and vimentin. GFAP immunopositivity of Bergmann-glia appeared in chicken and increased in rat in the lesioned area but the lesion was not surrounded by typical astrocytes and no demarcation was formed in the molecular layer, in contrast to the usual appearance of reactive gliosis, which was observed in the granular layer and in the white matter in both species. Vimentin immunopositivity of the Bergmann-glia also increased around the lesion in both species. The results suggest that a highly developed glial architecture fails to re-arrange into a demarcating scar, which offers an interesting model system to study the importance of glial demarcation. The observations also support that the resident glia is the main component of the glial reaction, and prove the capability of avian Bergmann-glia to express GFAP.     

Age-induced hypertrophy of astrocytes in rat supraoptic nucleus: a cytological, morphometric, and immunocytochemical study

BACKGROUND: In the adult rat, neuron-astroglia interactions in the supraoptic nucleus (SON) are characterized by the structural and functional plasticity of astrocytes in response to several physiological and experimental conditions. This study has analyzed the plasticity of the supraoptic nucleus astrocytes in response to the age-induced changes in neuronal activity. METHODS: The study was performed in 5-, 12-, 18- and 24-month-old rats. The cytology and organization of astrocytes in the SON were examined using glial fibrillary acidic and vimentin immunocytochemistry and ultrastructural and morphometric analysis. RESULTS: No significant age-related variations in the total number of neurons and astrocytes in the SON were detected, although a few degenerating neurons were found in old rats. An age-dependent increase in GFAP immunoreactivity was observed at the ventral glial lamina, perivascularly and between neuronal perikarya. Vimentin overexpression was also detected in ventral lamina astrocytes with advancing age. At the cell nucleus level, we observed an age-associated increase in nuclear size and in the number of coiled bodies, nuclear bodies, and "cleared" nucleoplasmic areas, as well as changes in the nucleolar organization. At the cytoplasmic level, characteristic ultrastructural features in astrocytes of old rats were the hypertrophy of intermediate filament bundles and the formation of an extensive network of Golgi stacks interlinked by tubulovesicular elements. Glial filaments were often associated with the nuclear envelope and polyribosomes. CONCLUSIONS: The increased GFAP and vimentin immunoreactivity and the morphometric and cytological changes in rat SON astrocytes may reflect a sustained upregulation of cellular activity with age, resulting in hypertrophy of glial perikarya and cell processes. Several factors that are known to influence the expression of the astrocytic phenotype, such as signals produced by degenerating neurons and activated microglia, as well as variations in neuronal activity are considered possible causes of the age-associated changes in SON astrocytes.     

Effects of axonal injury on astrocyte proliferation and morphology in vitro: implications for astrogliosis

Mechanisms inducing gliosis following injury in the central nervous sy stem are poorly understood. We evaluated the effect of axonal injury on astrocyte and Schwann cell proliferation and morphology in vitro. Purified rat dorsal root ganglion neurons grown on monolayers of rat neonatal cortical astrocytes (N-ASneonatal cultures) or sciatic nerve-derived Schwann cells (N-SC cultures) were mechanically injured. Non-injured cultures served as controls. Cell proliferation near lesions was monitored by autoradiography 1,2,4, and 8 days postinjury. Axonal injury caused a significant transient increase in astrocyte proliferation immediately proximal and distal to the lesion. The lesion did not induce marked changes in the intensity of glial fibrillary acidic protein (GFAP) immunoreactivity. However, processes from GFAP-positive cells usually arranged in random fashion in noninjured cultures were aligned perpendicularly to the cut distal to lesions. Ultrastructural analysis in lesioned N-ASneonatal cultures indicated that proximal to the lesion filament-filled astrocytes were intermingled with axons. Distal to the lesion astrocyte processes formed layers, between which an increased amount of collagen-like material appeared with time postlesion. Axons distal to the lesion degenerated by 2 days, coinciding with the early disappearance of neurofilament immunoreactivity. In noninjured and proximally in injured N-SC cultures, Schwann cells extended processes, engulfing some axons. Distal to the lesion, Schwann cells appeared more rounded and neurites remained until 4 days postinjury. Media conditioned by injured or non-injured N-ASneonatal cultures did not affect neuron-induced Schwann cell proliferation. These findings demonstrate that axonal injury and degeneration cause a transient increase in astrocyte proliferation and induce morphological changes in astrocytes consistent with the onset of gliosis.     

Gelatinase B in proliferative vitreoretinal disorders

OBJECTIVE: To evaluate the structural relationship of the distribution between tenascin (tenascin-C, an extra-cellular matrix glycoprotein involved in stromal-epithelial interactions in both normal and pathological conditions) and laminin, an important component of the basement membrane, in normal and neoplastic human prostate, and to establish whether changes in the basement membrane are accompanied by changes in tenascin staining. MATERIALS AND METHODS: Seventy-five snap-frozen prostate samples representing normal glands, nodular benign prostatic hyperplasia and prostate carcinoma were stained for tenascin. From these, 15 samples were selected for dual-immunofluorescence staining and a confocal laser scan microscope was used to simultaneously visualize tenascin and laminin immunoreactivity. RESULTS: Tenascin was expressed in the extracellular matrix, mainly at the periphery of the glands, in tumour foci and blood vessels. In cases with intact basement membranes, e.g. normal glands and hyperplastic lesions, tenascin expression was weak. Low- and moderate-grade tumours were characterized by strong tenascin expression, while laminin expression was weak and/or showed discontinuities, indicating disturbances in basement membrane composition. High-grade tumours had sparse tenascin staining and a marked loss of laminin immunoreactivity. CONCLUSION: These results indicate that periglandular tenascin expression correlates with the integrity of the basement membrane in the human prostate. By influencing stromal-epithelial interactions, tenascin may play a role in maintaining tissue homeostasis in the prostate.     

Neuritic outgrowth associated with astroglial phenotypic changes induced by antisense glial fibrillary acidic protein (GFAP) mRNA in injured neuron-astrocyte cocultures

In the adult CNS, axons fail to regenerate after injury. Among the cell interactions that lead to this failure are those developed with astrocytes. In an effort to elucidate the mechanisms underlying these negative interactions, we have used astrocytes treated with antisense glial fibrillary acidic protein (GFAP) mRNA to inhibit the formation of gliofilaments, indispensable for the astroglial morphological response to injury, and have studied their permissivity for neuritic outgrowth. In a neuron-astrocyte coculture, a mechanical lesion led to hypertrophy of astrocytes neighboring the lesion. Neuronal cell bodies and neurites were absent both from the area of lesion and from its surroundings. Reactive astrocytes appeared, therefore, to be a nonpermissive substrate. Transfection that used antisense GFAP mRNA blocked astroglial morphological changes and was characterized by both a persistence of neuronal cell bodies in the vicinity of the lesion site and a growth of neurites into the same region. These morphological differences were associated with a 46% decrease in the GFAP translation capacity and a 50% increase in the concentration of GAP-43 in the treated cultures. Neurons were associated mainly with an extracellular laminin network, which was predominant at the lesion site in treated cocultures. In contrast, those astrocytes highly laminin-immunoreactive appeared to be a nonpermissive substrate for neurons. These results show that inhibition in GFAP synthesis, leading to a reduction of astroglial hypertrophy, relieves the blockade of neuritic outgrowth that normally is observed after a lesion. The mechanisms may involve changes in the secretion of extracellular matrix molecules by astrocytes.     

Characterization and distribution of basic fibroblast growth factor-containing cells in the rat hippocampus

Basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor family, is present in relatively high levels in the brain where it may play an important role in the maintenance, repair, and reorganization of the tissue. Although bFGF is associated mainly with astrocytes throughout most of the central nervous system (CNS), a narrow but prominent band of pyramidal neurons, which coincides with the CA2 subregion of Ammon's horn in the hippocampus, stains intensely for bFGF. In order to gain an understanding of which cells express bFGF and whether or not BFGF is a good marker for CA2 neurons, we have used a mouse monoclonal antibody directed against recombinant human bFGF to characterize the distribution and localization of bFGF expression in the hippocampus. We find that about one-quarter of the neurons in CA2 are bFGF positive, and they appear smaller and have more irregular-shaped nuclei than their unstained counterparts. In addition, all glial fibrilary acidic protein (GFAP)-positive astrocytes in the hippocampus stain for bFGF, and the distribution of these astrocytes is heterogeneous in the hippocampus. Finally, in both astrocytes and CA2 pyramidal neurons, bFGF immunoreactivity is localized primarily in the nucleus and to a lesser extent in the cytoplasm and processes of stained cells.     

Becoming a grandparent: a longitudinal study of expectations and early experiences as a function of sex and lineage

In this study the presence of glial fibrillary acidic protein (GFAP) in kidney is for the first time demonstrated in cryostat sections and cultures of isolated glomerular explants derived from rat kidneys. In double immunolabelling analysis of adult rat kidney sections using antiserum against GFAP and monoclonal antibody (mAb) against vimentin or desmin, the presence of immunoreactivity for GFAP could be observed in the glomerulus of the kidney and vascular cells situated in the peritubular space which expressed vimentin and desmin. Labelling of the sections with absorbed antiserum against GFAP completely abolished the staining in all these cells. The mAb against GFAP, clone GF12.24 which is known to label GFAP both in neural and non-neural cells, recognised its antigen only in the cells located in glomeruli. The investigations performed on early 2- or 3-day-old cultures from glomerular explants revealed different patterns of staining for GFAP in mesangial cells and podocytes: weak filamentous in mesangial cells and a strong non-filamentous perinuclear pattern in podocytes. Due to prominent perinuclear expression in podocytes GFAP may be considered as a marker of these cells. A different pattern of distribution of immunoreactivity for GFAP in podocytes and mesangial cells might be due to function-related posttranslational modifications of GFAP resulting in assembly or disassembly of GFAP filaments. The different pattern of staining for GFAP in the podocytes and mesangial cells, cells which exert a different influence on the capillaries of the glomeruli, suggests a role for GFAP in regulation of the tension and permeability of vascular walls. Previous investigations and present studies hint at GFAP as being a general marker of perivascular cells.     

Nerve gas-induced seizures: role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.     

A C-terminal region of the Saccharomyces cerevisiae transcription factor ADR1 plays an important role in the regulation of peroxisome proliferation by fatty acids

We examined the hypoxic tolerance phenomenon in vitro. Brief exposure to hypoxia induced the production of basic fibroblast growth factor (bFGF) mRNA and protein in rat cortical neurons and protected them from hypoxic injury. Cortical neurons were cultured from 18th-day rat embryos in a serum-free medium and subjected to brief (4 h) and/or prolonged (24 h) hypoxia. Neuronal damage was assessed by quantifying lactate dehydrogenase (LDH) activity in the medium. After brief hypoxia, LDH release was identical to that of the controls, whereas prolonged hypoxia caused a significant increase in LDH release, indicating neuronal death. However, if brief hypoxia was applied 2 days prior to the prolonged hypoxia, no increase in LDH release was observed. The bFGF mRNA expression was assessed with Northern blot and protein immunoreactivity with Western blot analysis. The brief period of hypoxia caused a 2.5-fold increase in bFGF mRNA and considerable bFGF protein expression 1 day later, but prolonged hypoxia caused increase in the expression of bFGF mRNA at 2 days and no protein expression until 3 days after the start of the hypoxia. When cells were subjected to prolonged hypoxia 2 days after brief hypoxia, however, no increase in bFGF mRNA was observed, while bFGF protein was expressed continuously. We also observed that exogenously applied bFGF reduced neuronal injury produced by prolonged hypoxia. The results obtained with this model suggest that brief hypoxia induces bFGF protein and thus tolerance to subsequent lethal hypoxia. Basic FGF might play a role as a tolerance-associated factor in this process. Thus, an in vitro model is useful for assessing the response of cortical neurons to hypoxic stress and for researching new factors related to ischemic tolerance.     

Accuracy of automated finger blood pressure devices

Substance P and glial fibrillary acidic protein (GFAP) immunohistochemistry was applied to the medulla of neonatal infants who died of sudden infant death syndrome (SIDS). A quantitative analysis of cells demonstrating immunoreactivity to GFAP and substance P in 15 neonatal SIDS cases revealed increased GFAP immunoreactivity in the reticular formation, the dorsal vagal nucleus, and the solitary nucleus and an increase in substance P immunoreactivity in the spinal trigeminal nucleus and the solitary nucleus as compared with that in age-matched controls. GFAP immunopositivity suggests astrogliosis which implies a pathologic insult to neurons in the area of astrogliosis. The failure of neurons in these sites to show enhanced substance P immunopositivity may indirectly indicate altered neurons. Further study of prenatal events may be of importance in clarifying the pathogenesis of neonatal SIDS.     

Facial balance and harmony: an attainable objective for the patient with a high mandibular plane angle

We have analyzed the immunohistochemical expression of chondroitin sulfate proteoglycan (CSPG), fibronectin (FN), laminin (LN), tenascin (TN), and glial fibrillary acidic protein (GFAP) along the anterior commissure (AC) of hamster embryos (n=175; from embryonic day (E)12 to E16). Frozen sections were cut at different planes from embryonic brains between E12 and E16, treated for immunohistochemistry, and observed under epifluorescence microscopy. During the pre-crossing stage (E12-E13), CSPG was expressed as a sagittal stratum between the interhemispheric fissure and the prospective AC region. TN appeared rostral to the third ventricle and along the medial subventricular zone of the lateral ventricles. LN and FN both presented a faint expression, and GFAP was not detected. Although AC axons started crossing the midline region (E13.5-E14), CSPG, FN, LN, and, much less intensely, GFAP circumscribed the AC bundle, forming a tunnel through which AC fibers elongate. TN was no longer seen at the midplane but remained visible laterally. During the post-crossing stage (E14.5-E16), CSPG and TN were no longer seen at the midline, although both could be observed between the AC limbs, seeming to form boundaries for AC lateral growth. LN and FN were then absent near the AC bundle. During this late stage, GFAP expression became most intense, forming a distinct tunnel around the AC. We have shown that the expression of extracellular matrix molecules and GFAP follow a time- and space-regulated course related to AC development, plausibly representing influential factors for growth and guidance of commissural fibers.     

Importance of specific amino acids in protein binding sites for heparin and heparan sulfate

The present study tests whether lesions small enough to allow the rapid reestablishment of a normally aligned tract glial framework would provide a permissive environment for the regeneration of cut adult CNS axons. We made penetrating microlesions which cut a narrow beam of axons in the adult rat cingulum, but caused minimal damage to the tract glial framework and no cavitation. The proximal tips of cut axons were identified by enhanced immunoreactivity for low affinity neurotrophin receptor, p75. From 1 day they became expanded into large growth-cone-like structures. At later times some axons turned back and extended in the reverse direction. Up to 14 days (after which time p75 could no longer be used as a marker), no axons advanced beyond the line of the lesion. From 1 to 2 days, OX42 immunostaining and electron microscopy showed that the lesion site was densely infiltrated by macrophages, which disappeared by 3 to 4 days. This was followed by a local hypertrophy of the OX42 immunoreactive resident tract microglial cells and an increase in both GFAP and vimentin immunoreactivity of the tract astrocytes. These responses were greatly reduced by 8 days, when the longitudinal alignment of glial processes across the lesion site was similar to that of an undamaged tract. The large growth-cone-like structures formed at the ends of the cut axons resemble those of developing axons exposed to chemorepulsive factors. This suggests that cellular elements in adult tract lesions may also exert chemorepulsive influences blocking regeneration of axons even in an apparently "open" tract framework.     

Reactive astroglia-neuron relationships in the human cerebellar cortex: a quantitative, morphological and immunocytochemical study in Creutzfeldt-Jakob disease

In order to investigate the role of neuron-glia interactions in the response of astroglial to a non-invasive cerebellar cortex injury, we have used two cases of the ataxic form of Creutzfeldt-Jakob disease (CJD) with distinct neuronal loss and diffuse astrogliosis. The quantitative study showed no changes in cell density of either Purkinje or Bergmann glial cells in CJ-1, whereas in the more affected CJ-2 a loss of Purkinje cells and an increase of Bergmann glial cells was found. The granular layer in both CJD cases showed a similar loss of granule cells (about 60%) in parallel with the significant increase in GFAP+ reactive astrocytes. GFAP immunostaining revealed greater reactivity of Bergmann glia in CJ-2 than in CJ-1, as indicated by the thicker glial processes and the higher optical density. Granular layer reactive astrocytes were regularly spaced. In both CJD cases there was strict preservation of the spatial arrangement of all astroglial subtypes--Fa?anas cells, Bergmann glia and granular layer astrocytes. Reactive Fa?anas and Bergmann glial cells and microglia/macrophages expressed vimentin, while only a few vimentin+ reactive astrocytes were detected in the granular layer. Karyometric analysis showed that the increase in nuclear volume in reactive astroglia was directly related with the level of glial hypertrophy. The number of nucleoli per nuclear section was constant in astroglial cells of human controls and CJD, suggesting an absence of polyploidy in reactive astroglia. Ultrastructural analysis revealed junctional complexes formed by the association of macula adherens and gap junctions. In the molecular layer numerous vacant dendritic spines were ensheathed by lamellar processes of reactive Bergmann glia. Our results suggest that quantitative (neuron/astroglia ratio) and qualitative changes in the interaction of neurons with their region-specific astroglial partners play a central role in the astroglial response pattern to the pathogenic agent of CJD.     

Obtention and characterization of primary astrocyte and microglial cultures from adult monkey brains

Simple methods for obtention of primary cultures of isolated astrocytes and microglia from adult simian brain have been developed. Characterization of these two glial cell populations were performed by morphological observations and by immunocytochemistry. The astroglial cultures were obtained by an indirect method. After L-leucine methyl-ester treatment and trypsinizations, more than 99% of cells expressed glial fibrillary acidic protein (GFAP), whereas no macrophages or microglia could be detected. Likely, the 1% remaining cells were immature astrocytes or cells that lost their GFAP expression. Cultured simian astrocytes expressed vimentin, laminin, and fibronectin. We also found a constitutively low expression of major histocompatibility complex (MHC) class II by cultured astrocytes which was significantly enhanced by lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or tumor necrosis factor alpha (TNF-alpha) treatments. Microglial cultures were obtained by a direct method of isolation using Percoll gradient separations and compared to simian monocyte-derived macrophages or alveolar macrophages. Microglial cells differed from macrophages by their proliferation upon granulocyte-macrophage colony stimulating factor (GM-CSF) treatment and by their typical morphology when observed by scanning electron microscopy. As macrophages, they expressed in vitro CD68, CD64, CD14, CD11b, MHC class II, and fibronectin. However, contrary to macrophages, simian cultured microglia expressed laminin. This observation suggests that microglia represent a new potential source of this extracellular matrix protein in the brain.     

Deprenyl induces GFAP immunoreactivity in the intact and injured dopaminergic nigrostriatal system but fails to counteract axotomy-induced degenerative changes

There is increasing evidence of a trophic-like mechanism for some effects ascribed to deprenyl therapy in the central nervous system. For that, we studied the effect of chronic treatment with deprenyl in an animal model of Parkinson's disease induced by unilateral knife transection of the medial forebrain bundle (MFB) in adult rats. The experimental conditions included a 3-week pretreatment with deprenyl before stereotaxic transection of the MFB. Following surgery, deprenyl treatment was maintained for 3 weeks. Neurochemical and immunohistochemical procedures were used to study the dopaminergic system and reactive astrocytes in the nigrostriatal system. Deprenyl treatment failed to counteract the axotomy-induced degenerative changes of the nigrostriatal dopaminergic system. However, it was effective in increasing the density of reactive astrocytes in terms of glial fibrillary acidic protein (GFAP) immunoreactivity in the intact contralateral substantia nigra and also in further enhancing the axotomy-induced increase of GFAP immunolabeled astrocytes in the lesioned substantia nigra. This deprenyl-induced effect on GFAP immunoreactivity was confined to substantia nigra without effect in striatum. In addition, we found a medial to lateral gradient decrease in the distribution pattern of GFAP immunolabeled astrocytes. Axotomy increased the number of reactive astrocytes in either striatal area examined, but yet the preferential distribution pattern of reactive astrocytes in striatum was still evident.     

Conformational changes of the smooth endoplasmic reticulum are facilitated by L-glutamate and its receptors in rat Purkinje cells

Following a unilateral lesion of the visual cortex (cortical areas 17, 18, and 18a) in adult rats, neurons in the ipsilateral dorsal lateral geniculate nucleus (LGN) are axotomized, which leads to their atrophy and death. The time course of this neuronal degeneration was studied quantitatively, and the astroglial response was examined with glial fibrillary acidic protein immunohistochemistry. More than 95% of the neurons in the ipsilateral LGN survive during the first 3 days following a lesion of the visual cortex. However, in the next 4 days, massive neuronal death ensues, reducing the number of surviving neurons to approximately 33% of normal by the end of the first postoperative week. Between 2 weeks and 24 weeks postoperatively, the number of neurons present in the LGN declines very gradually from 34% to 17% of normal. Three days after a lesion of the visual cortex, the mean cross-sectional areas of ipsilateral LGN neurons are 13% smaller than normal (87%). By 1 week after the operation, surviving LGN neurons have atrophied to 66% of their normal area. Subsequently, the size of surviving neurons declines slowly to approximately 50% of normal at 24 weeks after the cortical lesion. Astrocytes in the ipsilateral LGN also react to cortical damage. At 1 day after a lesion of the visual cortex, glial fibrillary acidic protein immunoreactivity in the LGN is almost undetectable, but a distinct increase in immunoreactivity is seen at 3 days. Immunoreactivity peaks between 1 week and 2 weeks postoperatively and, thereafter, remains intense for at least 24 weeks. Thus, following a lesion of the visual cortex, the somata of neurons in the LGN remain essentially normal morphologically for about 3 days before the onset of rapid atrophy and death. Moreover, most of the neural cell death that occurs in the LGN after axotomy takes place in the last half of the first postoperative week.