Astrocytic reactivity and intermediate filament metabolism in experimental autoimmune encephalomyelitis: The effect of suppression with prazosin

In either actively or passively transferred experimental autoimmune encephalomyelitis (EAE), increased immunocytochemical staining of glial fibrillary acidic protein (GFAP) in astrocytes was detected early in the disease process in both the gray and white matter of the spinal cord. Staining was not restricted to areas of perivascular mononuclear infiltration, and was observed at all levels of the cord. This enhanced staining pattern was delayed in rats in which clinical signs of EAE had been suppressed by treatment with the alpha 1-adrenoceptor antagonist prazosin. This glial reaction in EAE was not accompanied by increased GFAP synthesis, as measured by in vitro labeling of spinal cord slices, nor an increase in GFAP content, as measured by densitometry of intermediate filament fractions separated by polyacrylamide gel electrophoresis. Total protein synthesis was increased, with vimentin being labeled especially heavily; in prazosin-treated EAE animals, the increase in total protein synthesis was reduced and delayed.     

Gliosis in the spinal cords of rats with experimental allergic encephalomyelitis: immunostaining of carbonic anhydrase and vimentin in reactive astrocytes

Spinal cord sections from rats sensitized to develop experimental allergic encephalomyelitis (EAE) were immunostained with antibodies against glial fibrillary acidic protein (GFAP), carbonic anhydrase, and vimentin, to see whether the latter two antigens could be detected in GFAP-positive reactive astrocytes. Sixteen days after sensitization (16 dpi) there was intense carbonic anhydrase immunostaining in GFAP-positive cells in the spinal cords of EAE rats, particularly in the white matter. At 13 and 20 dpi carbonic anhydrase immunostaining in astrocytes was less intense, and in the spinal cord white matter of control animals carbonic anhydrase was not detected in the few GFAP-positive cells. In the spinal cords of EAE rats vimentin immunostaining was observed in inflammatory cells and astrocytes. In the latter, GFAP and carbonic anhydrase were colocalized with vimentin. The data suggest that carbonic anhydrase expression in astrocytes is an acute response to injury and that vimentin can be detected in astrocytes, as well as inflammatory cells, as early as 16 dpi.     

Expression of citrullinated proteins in murine experimental autoimmune encephalomyelitis

In this study, we demonstrate for the first time the immunohistochemical expression of citrullinated proteins in the central nervous system (CNS) of mice with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). By using an established monoclonal antibody (F95) against natural and synthetic citrullinated proteins (Nicholas and Whitaker [2002] Glia 37:328-336), numerous, small, previously unrecognized "patches" of citrullinated proteins were discovered throughout EAE brains, whereas EAE spinal cords showed similar but much larger lesions. On dual color immunofluorescence, these lesions were found to contain citrullinated myelin basic protein (MBP) and were surrounded by astrocytes immunoreactive for both glial fibrillary acidic protein (GFAP) and F95. These lesions became evident about the time when EAE mice became symptomatic and increased in size and number with increasing disease severity. In some sections of spinal cord but not brains of severely debilitated EAE mice, a widespread gliotic response was seen, with astrocytes containing citrullinated GFAP spread throughout the gray and white matter. Western blot analysis of acidic proteins from the brains and spinal cords of EAE mice had higher levels of multiple citrullinated GFAP isoforms compared with controls, with more F95-positive bands in the EAE brains vs. spinal cords. These results raise the possibility that citrullination of both GFAP and MBP may contribute to the pathophysiology of EAE and that the brains of EAE mice may contain more pathology than previously realized.     

Accumulation of protein carbonyls within cerebellar astrocytes in murine experimental autoimmune encephalomyelitis

Recent work from our laboratory has implicated protein carbonylation in the pathophysiology of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The present study was designed to determine the changes in protein carbonylation during disease progression and to identify the target cells and modified proteins in the cerebellum of EAE animals, prepared by active immunization of C57/BL6 mice with MOG_35–55 peptide. In this model, protein carbonylation was maximal at the peak of the disease (acute phase), to decrease thereafter (chronic phase). Double‐immunofluorescence microscopy of affected cerebella showed that carbonyls accumulate in white matter astrocytes and to a lesser extent in microglia/macrophages, in both the acute and the chronic phase. Surprisingly, T cells, oligodendrocytes, and neurons were barely stained. By 2D oxyblot and mass spectrometry, β‐actin, β‐tubulin, GFAP, and HSC‐71 were identified as the major targets of carbonylation throughout the disease. Using a pull‐down/Western blot method, we found a significant increase in the proportion of carbonylated β‐actin, β‐tubulin, and GFAP in the chronic phase but not in the acute phase. These results suggest that as disease progresses from the inflammatory to the neurodegenerative phase there may be an inappropriate removal of oxidized cytoskeletal proteins. Additionally, the extensive accumulation of carbonylated GFAP in the chronic phase of EAE may be responsible for the abnormal shape of astrocytes observed at this stage. © 2010 Wiley‐Liss, Inc.     

[H]Thymidine labeling of astrocytes in experimental allergic encephalomyelitis

In acute experimental allergic encephalomyelitis (EAE), astrocytes in spinal cord tissue hypertrophy and stain intensely with antibody to the glial fibrillary acidic protein (GFAP). We attempted to determine if this activation is a result solely of hypertrophy of existing astrocytes or if astrocyte division might also occur. Lewis rats in various stages of acute EAE were injected with [³H]thymidine, the spinal cord sections were prepared, immunostained for GFAP and processed for radioautography. In spinal cords from rats administered thymidine on days 11–15 after sensitization a large number of mononuclear cells showed radioactive label. Many of these labeled cells, most likely monocytes and lymphocytes, were associated with inflammatory lesions, but others were located in the CNS parenchyma at great distances from the lesions. Most cells staining for the GFAP were hypertrophied with greatly extended cell processes, and the nuclei of some of these cells identified as astrocytes were overlaid with silver grains, indicating uptake of [³H]thymidine. In addition a few ependymal cells appeared to be labeled. No GFAP-stained cells from the Freund's adjuvant controls contained radioactive label. Similar studies using SJL/J mice with chronic relapsing EAE yielded very few labeled inflammatory cells or astrocytes. This study indicates that division takes place in some astrocytes in acute EAE, but occurs much less frequently in chronic EAE. Probably most of the increase in GFAP-stained material is a result of hypertrophy of astrocytes rather than of massive cell division.     

Increased citrullinated glial fibrillary acidic protein in secondary progressive multiple sclerosis

In this study, we demonstrate that grossly unaffected white matter from secondary progressive multiple sclerosis (SP-MS) patients is heavily citrullinated, as compared to normal white matter from control patients. Citrullination was most pronounced at plaque interfaces and was shown to colocalize with glial fibrillary acidic protein (GFAP)-immunoreactivity using dual color immunofluorescence. In contrast, the plaques themselves weakly stained for citrullinated proteins compared to control white matter and usually contained a blood vessel with surrounding astrocytes that were positive both for citrullinated proteins and GFAP. In SP-MS brain samples, but not in normal brains, long fibers of colocalized GFAP- and citrullinated proteins extended into the gray matter. Increased numbers of astrocytes containing citrullinated proteins and GFAP were also present at the junction between the gray and white matter in SP-MS brains. Western blot analysis of acidic brain proteins from nonplaque-containing white matter showed upregulation of multiple citrullinated GFAP proteins in SP-MS brains as compared to controls. Our results demonstrate that increased amounts of citrullinated GFAP are present in SP-MS brains, but also shows that these proteins are present in areas of MS brains that were grossly normal appearing. These data raise the possibility that citrullination of GFAP contributes to the pathophysiology of MS.     

睫状神经营养因子对坐骨神经切断吻合后大鼠脊髓前角胶质纤维酸性蛋白

背景：睫状神经营养因子具有多种生物活性,在神经系统发育、分化和损伤修复中具有重要意义。 目的：观察睫状神经营养因子对坐骨神经切断吻合后大鼠相应脊髓节段前角星形胶质细胞的特异标记物胶质纤维酸性蛋白表达的影响。 方法：将SD大鼠随机分为对照组、模型组、生理盐水组及药物组。除对照组外,对所有大鼠实施双侧坐骨神经切断吻合术,药物组手术区局部注射睫状神经营养因子100 ng/kg,1次/d,生理盐水组局部注射等量生理盐水。术后1,3,7,14,21,28 d取相应脊髓节段,免疫组织化学染色观察胶质纤维酸性蛋白的表达,苏木精-伊红染色、TUNEL染色对脊髓前角神经元进行计数。 结果与结论：大鼠坐骨神经切断吻合后相应脊髓节段星形胶质细胞胞体大,突起分枝多且粗大,神经元数目逐渐减少,凋亡神经元增多,胶质纤维酸性蛋白表达增高。与模型组和生理盐水组比较,药物组神经元存活数目增多,凋亡减少,胶质纤维酸性蛋白表达明显增加(P < 0.05或P < 0.01)。同时,药物组大鼠的运动功能障碍较轻,恢复较快。说明睫状神经营养因子可以通过促进大鼠脊髓前角胶质纤维酸性蛋白的表达起到神经保护作用。 关键词：胶质纤维酸性蛋白;睫状神经营养因子;星形胶质细胞;神经元凋亡;周围神经损伤     

Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats

The appearance of reactive astrocytes following brain injury was investigated in 4-week-old rats with special reference to their proliferation and chronological changes in the cytoskeletal proteins. Two days after the injury, glial fibrillary acidic protein (GFAP)-positive cells had increased in number around the lesion and spread to the entire ipsilateral cortex by 3 days after the injury. To investigate the distribution of mitotic cells and its chronological change, immunohistochemical staining with monoclonal antibody to bromodeoxyuridine (BrdU) was performed. BrdU-positive cells began to appear around the lesion and spread to the entire ipsilateral cortex by 3 days and their distribution was the same as that of GFAP-positive cells. To investigate the association of GFAP-positive cells with cell division, double labeling experiments using [3H]thymidine autoradiography and immunohistochemical staining with antiserum to GFAP were performed. Cells doubly labeled with GFAP and [3H]thymidine were localized in the area adjacent to the lesion, in the molecular layer of the cortex and in the white matter. By contrast, none of the cells were doubly labeled in the IInd to VIth layers of the cortex. Furthermore, only astrocytes in the former areas expressed vimentin transiently from 2 to 10 days after the injury. In the rats administered vincristine, cells arrested during mitosis were found in the regions which express vimentin. From these results, it was suggested that astrocytes in the molecular layer of the cortex and the white matter adjacent to the lesion proliferated in response to the injury and expressed vimentin transiently, then acquired GFAP, and that astrocytes in the IInd to VIth layers of the cortex became reactive astrocytes without mitosis.     

[3H]Thymidine labeling of astrocytes in experimental allergic encephalomyelitis

In acute experimental allergic encephalomyelitis (EAE), astrocytes in spinal cord tissue hypertrophy and stain intensely with antibody to the glial fibrillary acidic protein (GFAP). We attempted to determine if this activation is a result solely of hypertrophy of existing astrocytes or if astrocyte division might also occur. Lewis rats in various stages of acute EAE were injected with [³H]thymidine, the spinal cord sections were prepared, immunostained for GFAP and processed for radioautography. In spinal cords from rats administered thymidine on days 11–15 after sensitization a large number of mononuclear cells showed radioactive label. Many of these labeled cells, most likely monocytes and lymphocytes, were associated with inflammatory lesions, but others were located in the CNS parenchyma at great distances from the lesions. Most cells staining for the GFAP were hypertrophied with greatly extended cell processes, and the nuclei of some of these cells identified as astrocytes were overlaid with silver grains, indicating uptake of [³H]thymidine. In addition a few ependymal cells appeared to be labeled. No GFAP-stained cells from the Freund's adjuvant controls contained radioactive label. Similar studies using SJL/J mice with chronic relapsing EAE yielded very few labeled inflammatory cells or astrocytes. This study indicates that division takes place in some astrocytes in acute EAE, but occurs much less frequently in chronic EAE. Probably most of the increase in GFAP-stained material is a result of hypertrophy of astrocytes rather than of massive cell division.     

Vimentin-GFAP transition in primary dissociated cultures of rat embryo spinal cord

Primary dissociated cultures derived from 15-day-old rat embryo spinal cord with or without dorsal root ganglia (DRG) were grown on polylysine, Primaria and laminin substrates. On polylysine and Primaria substrates, spinal cord neurons formed aggregates connected by bundles of neurites in a distinctive pattern similar to that observed in cultures derived from embryonal rat brain and neonatal rat cerebellum. After 2 days in culture, the number of cells stained with GFAP antibodies progressively increased within the vimentin-positive monolayer surrounding the neuronal aggregates. These astrocytes had the typical appearance of astrocytes in primary dissociated cultures derived from late fetal or early neonatal murine brain, i.e. large flat or stellate cells with thick processes staining equally well with GFAP and vimentin antibodies. Astrocytes found within the neuronal aggregates in 4-5 day cultures were markedly different, i.e. small stellate cells with slender processes forming a delicate mesh throughout the aggregate. These GFAP-positive cells stained only weakly with vimentin antibodies. Spinal cord neurons formed aggregates on laminin substrates but failed to extend neurites and rapidly degenerated. The large flat cells in the surrounding monolayer gradually invaded the aggregates. These cells stained with both GFAP and vimentin antibodies. DRG neurons developed equally well on Primaria and laminin substrates, extending their neurites on the vimentin-positive flat cells forming the monolayer regardless of their reactivity with GFAP antibodies.     

Axonal regeneration in old multiple sclerosis plaques

Summary Cryostat sections of two old plaques removed at autopsy from the spinal cord of a 62-year-old man with multiple sclerosis of 24-year duration were studied by indirect immunofluorescence with antibodies to neurofilament proteins, glial fibrillary acidic protein (GFAP), glial hyaluronate-binding protein (GHAP), vimentin and laminin. The neurofilament monoclonal antibodies used in this study reacted with phosphorylated epitopes of the two large polypeptides of the neurofilament triplet (NF 150K, NF 200K). As previously reported [Dahl D, Labkovsky B, Bignami A (1989) Brain Res Bull 22:225–232], the neurofilament antibodies either stained axons in the distal stump of transected sciatic nerve in the early stages of regeneration or late in the process, i.e., after regenerating axons had reached the distal stump of the transected sciatic nerve. Both multiple sclerosis plaques were positive for GFAP and vimentin, but negative for GHAP, while astrocytes in myelinated spinal cord white matter stained with both GFAP and GHAP antibodies. Laminin immunoreactivity in the plaques and normal spinal cord was confined to blood vessels. One plaque was almost devoid of axons as evidenced by indirect immunofluorescence with neurofilament antibodies. Another plaque was packed with bundles of thin axons running an irregular course in the densely gliosed tissue. Axons in the plaque only stained with neurofilament antibodies reacting with sciatic nerve in the early stages of regeneration while axons in the surrounding myelinated white matter were decorated by all neurofilament antibodies, regardless of the time of appearance of immunoreactivity in crushed sciatic nerve. It is concluded that reactive astrocytes forming glial scars do not constitute a non-permissible substrate for axonal growth.Supported by NIH grant NS 13034 and by the Veterans Administration     

Experimental transmission of human subacute spongiform encephalopathy to small rodents

Summary The distribution of glial fibrillary acidic protein (GFAP) in the central nervous system (CNS) lesions of tuberous sclerosis (TS) was examined using antiserum against GFAP and the peroxidase antiperoxidase method of Sternberger. In cortical tubers there were islands of gemistocytic astrocytes staining intensely for GFAP and occasional giant cells having some cytoplasmic staining. The majority of the cortical giant cells had no GFAP. The islands were separated by areas devoid of astrocytes with perikaryal staining. A faintly staining fibrous network was found between these islands. The majority of cells in the subependymal nodules stained. The retinal phakoma stained but not as intensely as the subependymal nodules. There was no staining whatsoever in the giant cell subependymal tumors. Absence of GFAP staining in the subependymal giant cell tumors makes their classification as astrocytomas less certain.     

Glial fibrillary acidic protein in chronic relapsing experimental allergic encephalomyelitis in SJL/J mice

The gliotic scar in the demyelinated plaque is a prominent feature of the pathology of multiple sclerosis. Chronic relapsing experimental allergic encephalomyelitis (EAE) in the SJL/J mouse has many characteristics in common with multiple sclerosis in the human, including the development of intense gliosis during the course of the demyelinating disease. With the use of antibody to the astrocyte marker glial fibrillary acidic protein (GFAP) we have measured the increase of GFAP over an 11-month course of chronic EAE. Intense staining of astrocyte fibers was seen around EAE lesions, which were most frequently observed in the cerebellum, periventricular areas, and in the spinal cord. The relative amount of GFAP was estimated by preparation of cytoskeletal proteins from the affected CNS areas, separation of proteins by polyacrylamide gel electrophoresis, and quantitation of GFAP in relation to the 70-kD neurofilament protein (NF) in gel scans. The ratio GFAP/70-kD NF protein in control animals did not change significantly over 11 months, whereas this ratio gradually increased to 2.54 in animals with chronic relapsing EAE 6 months after immunization. Although some decrease of neural fibers may have contributed partially to this change in ratio, the amounts of GFAP were greatly increased. These results indicate that the SJL/J mouse with chronic relapsing EAE provides an excellent model with which to investigate the formation and development of the gliotic plaque analogous to that seen in demyelinated areas in multiple sclerosis tissue.     

实验性自身免疫性脑脊髓炎的小胶质细胞和星形胶质细胞反应

目的确定小胶质细胞和星形胶质细胞在实验性自身免疫性脑脊髓炎（ＥＡＥ）发病及病变发展中的作用。方法用牛脊髓髓鞘碱性蛋白（ＭＢＰ）免疫豚鼠发生ＥＡＥ,用免疫组化法观察ＥＡＥ不同病期小胶质细胞和星形胶质细胞对炎性脱髓鞘病灶的反应。结果发生ＥＡＥ的前３天,小胶质细胞即开始激活,在临床症状出现时其数量及激活程度达高峰,并持续至高峰期。恢复期数量逐渐减少,激活程度逐渐减弱。星形胶质细胞在症状高峰期开始激活并围绕在浸润细胞和病变血管周围,似有隔离小胶质细胞与病灶接触的作用,至恢复期激活明显。结论小胶质细胞激活在ＥＡＥ的发病及进展中起重要作用,而星形胶质细胞主要与疾病的恢复有关。     

Effects of transforming growth factor-β1 on the extracellular matrix and cytoskeleton of cultured astrocytes

The present study was performed on primary cultures and subcultures of cerebellar astrocytes in order to investigate the effects of transforming growth factor-β1 (TGFβ1) on proliferation, extracellular matrix (ECM) components, and cytoskeletal structures in relation to morphological changes. The expression and cellular distribution of the ECM components laminin and fibronectin and the cytoskeletal proteins glial fibrillary acidic protein (GFAP) and actin were investigated by immunoblotting, immunocytochemistry, and phalloidin staining. The proliferation of primary cultures was strongly inhibited by TGFβ1. Treated cells became enlarged and spread onto the substratum. TGFβ1 promoted the appearance of actin stress fibers and increased the cell actin content. It elicited a slight increase in GFAP expression and induced dispersion of thin filaments of GFAP. TGFβ1 also stimulated the production of laminin and fibronectin and their incorporation into the ECM of primary cultures grown in medium with or without serum Astrocytes grown in serum-containing medium for 1 day after subculturing responded strongly to TGFβ1. Changes promoted by TGFβ1 in cell shape, cytoskeleton, and ECM production of cultured astrocytes may have relevance for understanding the mechanisms of action of TGFβ1 during brain development.     

Developmental changes of glial fibrillary acidic protein and myelin basic protein in perinatal leukomalacia: relationship to a predisposing factor

Focal white matter necrosis is frequently seen in the brains of infants with perinatal cerebral hypoperfusion. Periventricular leukomalacia (PL) occurs in the deep white matter of premature and term neonates and subcortical leukomalacia (SL) in the subcortical white matter of young infants. Using immunoperoxidase methods in normal infants, glia positive for glial fibrillary acidic protein (GFAP) were found first in the deep zones of white matter and with increasing age they became more prominent in the subcortical zone. They increased diffusely in the deep or subcortical zones of the cases of PL or SL, respectively. The number of myelin basic protein-positive glia is much larger than that of GFAP-positive glia in the cases of old PL. These findings suggest that an increased number of positive glia may be a reaction to hypoxic, ischemic, or toxic insults, or this shifting, transient increase of positive glia in cerebral white matter may be one of several predisposing factors leading to perinatal leukomalacia. Furthermore, positive staining of GFAP and MBP for reactive astrocytes in old PL suggests that at a certain stage of gliogenesis both GFAP and myelin basic protein may be present within the same cell.     

Inhibition of reactive astrocytosis in established experimental autoimmune encephalomyelitis favors infiltration by myeloid cells over T cells and enhances severity of disease

Reactive astrocytosis, involving activation, hypertrophy, and proliferation of astrocytes, is a characteristic response to inflammation or injury of the central nervous system. We have investigated whether inhibition of reactive astrocytosis influences established experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We made use of transgenic mice, which express herpes simplex virus-derived thymidine kinase under control of a glial fibrillary acidic protein promotor (GFAP HSV-TK mice). Treatment of these mice with ganciclovir leads to inhibition of reactive astrocytosis. When GFAP HSV-TK mice were treated for seven days following onset of EAE with ganciclovir, disease severity increased. Although aquaporin-4 staining on astrocyte endfeet at the glia limitans remained equally detectable, GFAP immunoreactivity and mRNA expression in CNS were reduced by this treatment. Ganciclovir-treated GFAP HSV-TK mice with EAE had a 78% increase in the total number of infiltrating myeloid cells (mainly macrophages), whereas we did not find an increase in infiltrating T cells, using quantitative flow cytometry. Per cell expression of mRNA for the macrophage-associated molecules TNFα, MMP-12 and TIMP-1 was elevated in spinal cord of GFAP HSV-TK mice treated with ganciclovir. Relative expression of CD3ε was downregulated, and expression levels of IFNγ, IL-4, IL-10, IL-17, and Foxp3 were not significantly changed. mRNA expression of CCL2 was upregulated, and CXL10 was downregulated. Thus, inhibition of reactive astrocytosis after initiation of EAE leads to increased macrophage, but not T cell, infiltration, and enhanced severity of EAE. This emphasizes the role of astrocytes in controlling leukocyte infiltration in neuroinflammation.     

GFAP mRNA fluctuates in synchrony with chronic relapsing EAE symptoms in SJL/J mice

Activation of astrocytes and hypertrophy of their processes is a result of a number of pathological conditions in the central nervous system. Astrocytic gliosis is especially prominent in multiple sclerosis (MS), where astrocytic fibers form a dense matrix around demyelinated axons. Experimental allergic encephalomyelitis (EAE), a laboratory model for MS, is also accompanied by astrocytic hyperactivity. We have previously shown the formation of plaque-like structures which stain heavily for glial fibrillary acidic protein (GFAP) in the brains and spinal cords of SJL/J mice after several episodes of chronic relapsing EAE (Smith and Eng: J Neurosci Res 18:203, 1987). To further investigate the mechanisms of this phenomenon, we have measured the levels of mRNA for GFAP throughout the course of three episodes and recoveries of EAE in the SJL/J mouse. Mice were immunized with spinal cord homogenate and subsequently developed EAE. After recovery they were again immunized at appropriate intervals, resulting in successive episodes of EAE, with partial or complete recovery between the paralytic stages. At appropriate times in the course of the different stages of EAE, spinal cords were dissected and RNA was prepared from each spinal cord. RNA Was analyzed by Northern blots to determine the levels of mRNA for GFAP and, as a control, for the 70 kDa neurofilament (NF-L). With the onset of the first EAE episode GFAP mRNA in spinal cords from animals with mild symptoms increased to sixfold the control level (P < 0.02) and to 20-fold in those with paralysis (P < 0.01). With recovery, the GFAP mRNA level decreased to twice the control. With each subsequent episodes, a chronic but stable neurological deficit was established, with GFAP mRNA at about eightfold the control levels (P < 0.01). Over the course of several episodes, the GFAP rose to about 2.8 times the control, while vimentin increased by a factor of 3.6. Thus multiple episodes of EAE resulted in upregulation of GFAP mRNA and accumulation of GFAP, which are associated with astrocyte activation and hypertrophy. Similar events may occur in the human demyelinative disease MS, where multiple episodes of inflammatory cell invasion occur, resulting in a neurological deficit. © 1995 Wiley-Liss, Inc.     

实验性变态反应性脑脊髓炎大鼠星形胶质细胞的变化

目的观察实验性变态反应性脑脊髓炎(EAE)大鼠脊髓中星形胶质细胞的变化,探讨EAE大鼠的发病相关生物学机制。方法采用免疫组化法,对豚鼠全脊髓匀浆诱导的Wistar大鼠EAE的过程中,脊髓内星形胶质细胞变化情况进行研究。结果EAE大鼠症状高峰期时星形胶质细胞开始激活,恢复期时激活达到高峰,而且活化的星形胶质细胞未见表达主要组织相容性抗原(MHC)。结论活化的星形胶质细胞可能与EAE大鼠的恢复有关。     

Patterns of gliosis in Alzheimer's disease and aging cerebrum

The distribution of astrocytic gliosis in Alzheimer's disease (AD) and aging cerebrum, as marked by immunoperoxidase staining for glial fibrillary acidic protein (GFAP), was examined in whole-hemisphere coronal sections. Cortical gliosis in AD had an obvious laminar pattern. There were two heavy bands of staining, one in layers II-III and another in layer V. Normal aging cases sometimes displayed considerable cortical gliosis, but no specific patterns were apparent. Most AD cases, and some normal aging cases, displayed hypertrophy of immunoreactive astrocytes at grey matter-white matter interfaces, especially the cortico-medullary junction. Subcortical grey matter gliosis was common in both normal aging and AD, but there was no consistent pattern in either group. The deep cerebral white matter, which is stained evenly and heavily in young, healthy individuals, showed uneven staining in both normal elderly and AD brains. In both AD and aging, perivascular gliosis was prominent throughout the cerebrum and especially in the putamen. In conclusion, both AD and aging cerebri show extensive gliosis: AD cortical gliosis has a specific laminar pattern, but there does not appear to be an AD-specific pattern of subcortical gliosis.