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Objective To investigate the effect of electromagnetic wave power density on the expression of glial fibrillary acidic protein(GFAP)in the hippocampus of SD rats under 1800 MHz electromagnetic wave irradiation,and whether it exhibits a"window effect".Methods Ninety-eight 4-week-old SPF-grade SD rats were randomly divided into 14 groups,with 7 rats in each group.Seven groups were exposed groups(frequency:1800 MHz,power densities:0.1 mW/cm2,0.3 mW/cm2,0.5 mW/cm2,0.7 mW/cm2,0.9 mW/cm2,1.0 mW/cm2,1.2 mW/cm2)and corresponding 7 groups were control groups(power density:0 mW/cm2).Exposure was conducted for 12 hours daily for 3 weeks.After exposure,Western Blot was used to detect the expression level of GFAP in the hippocampal tissue,and immunohistochemistry staining was performed to determine the average optical density(MOD)value of GFAP-positive expression products in the DG,CA3,and CA1 regions of the hippocampal tissue,to determine the power density window of GFAP expression in the hippocampus of SD rats under 1800 MHz exposure.Results At power densities of 0.1 mW/cm2 and 0.3 mW/cm2,Western Blot results showed increased expression of GFAP in the rat hippocampus(P<0.05),and immunohistochemistry staining demonstrated increased MOD values of GFAP in the three regions(P<0.05).Conclusion Long-term exposure to 1800 MHz elect-romagnetic radiation has a"window effect"on the expression of GFAP in the DG,CA3,and CA1 regions of the hippocampus in SD rats,with power density windows of 0.1 mW/cm2 and 0.3 mW/cm2.
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Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare immune-mediated inflammatory disease of central nervous system reported in recent years, and its specific biological marker is anti-GFAP autoantibody. In this paper, the etiology, pathogenesis, clinical manifestations, auxiliary examination and treatment of the disease are comprehensively expounded, so as to improve the understanding of clinicians, especially neurologists.
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@#Introduction: Astrocytes are responsible for many essential functions of neurons in CNS. It has been recognised that chronic stress affects the morphology of astrocyte. Natural antioxidant such as honey has been used as one of the therapeutic strategies to lessen the damaging effect of chronic stress on our body. Therefore, the aim of the study is to explore the effect of natural antioxidant, Tualang honey (TH) on the morphology of astrocytes following chronic stress exposure. Methods: Thirty-two male rats were randomly divided into the 4 groups: (i) control, (ii) stress, (iii) honey, (iv) stress plus honey groups.TH was administered via oral gavage at dose of 1.0 g/kg body weight pre and post experiment. Chronic stress was exposed to animals in group (ii) and (iv) for consecutive 21 days. Anti GFAP immunohistochemistry method was employed to label astrocytes in the medial prefrontal cortex. The number of GFAP+ astrocytes and several parameters related to astrocyte processes were measured. Results: The present study showed that chronic stress reduced the GFAP immunoreactive astrocyte number and percentage of GFAP immunoreactive material. Chronic stress also caused a reduction in astrocyte process ramification as indicated by a reduction in astrocyte total number of processes, average length of processes and maximum number of intersections. However, antioxidant treatment using TH could not reverse these stress-induced changes to the astrocytes. Conclusion: These results demonstrate that chronic stress decreases the number of GFAP immunoreactive astrocyte and cause shrinking of astrocyte processes in stress-sensitive brain region, but these changes cannot be reversed by antioxidant treatment.
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Objective @#To observe the expression of glial fibrillary acidic protein (GFAP) in the brain tissue of rats with traumatic brain injury (TBI) and the differential changes between brain regions.@*Methods @#The TBI model of rats was prepared by the modified Feeney free fall method , and it was randomly divided into the sham⁃operated qPCR were used to observe the morphological changes of activated astrocytes and the expression of GFAP in different brain regions after TBI.@*Results @#Immunohistochemical staining showed that astrocytes were activated in all brain regions on the right side of TBI , and the only brain regions that spilled over to the contralateral side ( left) were cortical region 1 and midbrain regions. RT⁃qPCR results showed that GFAP mRNA was highly expressed in all brain regions on the right side of TBI , affecting the contralateral cortex and midbrain regions. Western blot results showed that GFAP protein was highly expressed in all brain regions on the right side of TBI , and it spread to the contralateral midbrain regions. @*Conclusion @#TBI can cause the activation of astrocytes and increase GFAP expression in the right brain regions , while also affecting the contralateral (left) cortex 1 and midbrain regions.
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Aim To observe cellular damage and astrocyte activation at different time points of cerebral ischemia and reperfusion. Methods The middle cerebral artery of male SpragueDawley rats was occluded for 90 min followed by different time points of reperfusion. Eighty-five SPF male SD rats were randomly divided into control group (Sham), IR3, 6, 12, 24 and IR48h (MCAO followed by 48 h of reperfusion) group. Cerebral ischemia and reperfusion injury was observed by HE staining, and the structure of astrocytes was estimated with transmission electron microscopy (TEM). GFAP expression was detected by immunofluorescence staining and Western blot. Results Cerebral ischemia following by different time points of reperfusion led to different degrees of cellular damage, which was the most serious at 24 h of reperfusion. TEM showed destruction of astrocytes structure, swollen organelles and broken mitochondrial ridge. After cerebral ischemia-reperfusion, the expression levels of GFAP were significant up-regulated in the ischemic penumbra cortex and the highest was at 48 h of reperfusion, indicating astrocytes were activated. In addition, the results showed the gradual decrease in GFAP expression in the infarct core. Conclusions After cerebral ischemia-reperfusion, cellular damage is aggravated, and astrocytes are gradually activated in the ischemic penumbra. With the extension of reperfusion time, the boundaries of infarct area and ischemic area are gradually clear, and scarring may occur.
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This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.
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Rats , Animaux , Astrocytes , Encéphalopathie ischémique/métabolisme , Encéphale , Lésion d'ischémie-reperfusion/métabolisme , Infarctus du territoire de l'artère cérébrale moyenneRésumé
This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.
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Animaux , Rats , Aquaporine-4/génétique , Astrocytes , Oedème cérébral/traitement médicamenteux , Encéphalopathie ischémique/métabolisme , Flavonoïdes , Infarctus du territoire de l'artère cérébrale moyenne/traitement médicamenteux , Rat Sprague-Dawley , Reperfusion , Canaux cationiques TRPV/usage thérapeutiqueRésumé
ObjectiveTo investigate the effects of Anmeidan (AMD) on neuronal structure and neuronal marker protein expression in the hippocampal CA1 region of sleep-deprived (SD) rats. MethodRats were randomly divided into control group, model group, an AMD group (9.09 g·kg-1·d-1), and melatonin group (0.27 g·kg-1·d-1). Rats in the control group and the model group received equal volumes of physiologicol saline. The SD model was induced by the self-made sleep deprivation box for four weeks. Ethovision XT system detected and analyzed the spontaneous behaviors of rats. The histomorphology of neurons in the hippocampal CA1 region was observed by hematoxylin-eosin (HE) staining and Nissl staining, and the changes in Nissl bodies were observed by Nissl staining. The ultrastructure of hippocampal cells was observed by transmission electron microscopy (TEM). Immunohistochemistry was used to detect the expression of glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), nestin, and neuronal nuclei (NeuN) in the CA1 region. ResultCompared with the control group, the model group showed longer distance, increased average activity speed, cumulative duration, average body fill, and higher activity frequency (P<0.01). Besides, the neurons in the CA1 region were reduced in number with disorganized arrangement, wrinkled nuclei, deeply stained cytoplasm, reduced Nissl bodies, swollen and deformed mitochondria, shortened cristae, and swollen Golgi vesicles. Furthermore, the mean integral absorbance (IA) value of GFAP increased and those of MAP2, nestin, and NeuN decreased (P<0.01). Compared with the model group, the AMD group showed shortened distance traveled, lower average activity speed, shorter cumulative duration, decreased average body fill, and reduced activity frequency (P<0.05, P<0.01). Moreover, the neurons in the CA1 region were relieved from damage with increased cell number, clear nuclei and cytoplasm, increased Nissl bodies, and relieved mitochondrial damage. The IA value of GFAP decreased and those of MAP2, nestin, and NeuN increased (P<0.05, P<0.01). ConclusionAMD can improve structural damage of neurons in the hippocampal CA1 region of sleep-deprived rats, which may be achieved by decreasing GFAP expression and increasing MAP2, nestin, and NeuN expression.
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Increasing evidence has shown that astrocytes are implicated in regulating oligodendrocyte myelination, but the underlying mechanisms remain largely unknown. To understand whether microRNAs in astrocytes function in regulating oligodendroglial differentiation and myelination in the developing and adult CNS, we generated inducible astrocyte-specific Dicer conditional knockout mice (hGFAP-CreERT; Dicer fl/fl). By using a reporter mouse line (mT/mG), we confirmed that hGFAP-CreERT drives an efficient and astrocyte-specific recombination in the developing CNS, upon tamoxifen treatment from postnatal day 3 (P3) to P7. The Dicer deletion in astrocytes resulted in inhibited oligodendroglial differentiation and myelination in the developing CNS of Dicer cKO mice at P10 and P14, and did not alter the densities of neurons or axons, indicating that Dicer in astrocytes is required for oligodendrocyte myelination. Consequently, the Dicer deletion in astrocytes at P3 resulted in impaired spatial memory and motor coordination at the age of 9 weeks. To understand whether Dicer in astrocytes is also required for remyelination, we induced Dicer deletion in 3-month-old mice and then injected lysolecithin into the corpus callosum to induce demyelination. The Dicer deletion in astrocytes blocked remyelination in the corpus callosum 14 days after induced demyelination. Together, our results indicate that Dicer in astrocytes is required for oligodendroglia myelination in both the developing and adult CNS.
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@#Objective To investigate N terminal pro B type natriuretic peptide (NT-proBNP),glial fibrillary acidic protein (GFAP)and hypoxia inducible factor-1 (hypoxia inducible factor-1α,HIF-1α) expression and there significance in inflammatory injury in patients with cerebral hemorrhage.Methods We selected 80 patients with acute intracerebral hemorrhage treated in our hospital from January 2018 to December 2019 as the observation group and 80 healthy people who underwent physical examination in our hospital in the same period as the control group.After routine treatment,NT-proBNP,GFAP and HIF-1α in patients serum and cerebrospinal fluid were detectedα、Tumor necrosis factor-α(TNF-α) interleukin-6 (IL-6),and correlation analysis was carried out.Results NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid of patients in the observation group、TNF-α and IL-6 levels in the control group were higher than those in the control group (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid of the observation group after treatment,as well as TNF-α and IL-6 levels were lower than those before treatment (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid increased with the aggravation of the disease、TNF-α and IL-6 levels were positively correlated with the degree of intracerebral hemorrhage (P<0.05).NT-proBNP,GFAP and HIF-1α in serum and cerebrospinal fluid were associated with inflammatory injury in intracerebral hemorrhage.There was a significant positive correlation with IL-6 level (P<0.05).NT-proBNP,GFAP and HIF-1α.It was closely related to inflammatory injury in patients with intracerebral hemorrhage and was an independent risk factor for intracerebral hemorrhage complicated with inflammatory injury (P<0.05).Conclusion The levels of NT-proBNP,GFAP and HIF-1α are closely related to inflammatory injury and prognosis in patients with cerebral hemorrhage.The detection of NT-proBNP,GFAP and HIF-1α levels has certain clinical value in judging the disease and prognosis.
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@#Objective To explore the clinical features through analyzing the clinical data of 5 patients with autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy and reviewing the literatures.Methods We retrospectively analyzed the general data,clinical symptoms,cerebrospinal fluid results,electroencephalogram results,imaging data and treatment results of 5 patients with GFAP astrocytopathy at our hospital and reviewed the literatures.Result The average age of onset was 57 in five patients.The main clinical symptoms were limb fatigue,memory loss,increased sleep,urine and stool disorders,fever and so on,and 1 patient was accompanied by epileptic seizure in addition to the above manifestations.Cerebrospinal fluid examination showed that protein and cell number were increased in different degrees,4 patients showed positive oligoclonal bands and specific oligoclonal bands in cerebrospinal fluid,and 24 hours intrathecal synthesis rate increased in different degrees.The electroencephalogram showed varying degrees of slow waves.Abnormal signals in the temporal lobe,lateral ventricle,basal ganglia and corpus callosum were observed by craniocerebral MRI.Abnormal signals in the medulla oblongata,cervical medulla and thoracic medulla were observed in 3 patients.All the 5 patients received hormone therapy,and their symptoms were improved to varying degrees.Conclusions The clinical symptoms of patients with GFAP astrocytosis were mainly encephalopathy,meningitis and encephalomyelitis,and the cerebrospinal fluid had different degrees of immune-mediated inflammatory reaction.Imaging examination showed that the brain,meninges,spinal cord and optic nerve were involved,and most of patients respond well to hormones.
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Aim To investigate the effect of ferulate-heparin-poloxamer (SF-HP) thermosensitive hydrogels on nerve regeneration in ratswith spinal cord injury, and provide experimental basis for clinical application. Methods SD rats were randomly divided into five groups: sham group, SCI group, SCI + HP group, SCI + SF group and SCI + SF-HP group. Rats were performed moderate contusion injuries using a vascular clip for 2 min to establish SCI animal model, then rats were given BBB score and inclined plate scoring function test after SCI. BDA tracing was employed to observe the recovery of nerve conduction function. Moreover, immunohistochemical staining and Western blot-were used to measure GAP43, Nestin and GFAP levels. Results BBB score and inclined plane test score significantly increased in SF-HP treated group as compared with the model group (P < 0. 01). Staining data showed that the structure of spinal cord was void, and this phenomenon was reversed after SF-HP administration. Data showed that the level of GAP43 and Nestin increased after SF treatment (P < 0. 05), the expression of GFAP decreased (P <0. 05), and the treatment effect of SF-HP hydrogels were better than those of SF alone (P < 0. 0 5) . BDA tracing data showed that the number of positive neurons markedly increased and the repair of nerve conduction function was significantly improved in SF-HP hydrogel group compared with SF group. Conclusion HP hydrogels enhance the effect of SF on the nerve regeneration in damaged spinal cord in rats.
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Objective: To investigate the possible role of astrocytes after brain infarction in stroke-prone, spontaneously hypertensive (SHR-SP) rats and the association with angiogenesis and the architecture. Methods: We maintained SHR-SP rats on high sodium water starting to accelerate the stroke onset. The 3D quantification of microvasculatures (diameter, branch number) by cofocal microscope after FITC-dextran was injected into the rats via the left femoral vein. Glial fibrillary acidic protein (GFAP) expression and microvessel density (MVD) using counting the number of factor -positive endothelial cells were evaluated by immunofluorescence and immunohistochemistry, respectively. Results: Cerebral infarction occurred at week 7 after high sodium water intake (13 g/L NaCl) in SHR-SP group. When compared with the non-infarcted contralateral hemisphere and SHR-SP on normal sodium intake and WKY rats, GFAP expression and MVD were significantly increased, respectively, and the diameter and the branch number of vessels were decreased, respectively, in cerebral infarcts with boundary zones of SHR-SP rats (P<0.01). Linear correlation analysis showed that GFAP expression was positively correlated with MVD and the diameter and the branch number of vessels in cerebral infarcts in SHR-SP (P<0.01). Conclusion: Astrocytes hyperplasia may be associated with increased regional angiogenesis and the changes of architecture in SHR-SP rats with high sodium water (13 g/L NaCl) that induces focal cerebral infarcts.
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Objective: To investigate the effect of aquaporin 4(AQP4)in neuropathic pain and explore the rela- tionship with the activation of spinal astrocytes and release of proinflammatory cytokines. Methods: The effect of AQP4 gene knockout(KO)on the pain-related behavior was investigated using the sciatic nerve branch injury model(SNI)of AQP4 KO and wild type(WT)mice. The expression of astrocyte activation-related protein,glial fibrillary acidic protein(GFAP),and the level of proinflammatory cytokines,TNF-α and IL-6,all in the mouse spinal cord samples,were detect- ed by Western blot(WB)and ELISA,respectively. Results: After SNI surgery,compared with the WT group,a signifi- cant attenuation in mechanical allodynia was found in the KO group(P<0.01),however,no difference was detected be- tween two sham groups(Sham)of WT and KO mice(P>0.05). These results indicated that the AQP4 gene knockout re- lieved neuropathic pain. Fouteen days after SNI surgery,WB results showed that the GFAP level in mouse spinal cord was significantly higher in the WT-SNI group than in the WT-Sham group(P<0.01),whereas the GFAP level in the KOSNI group was significantly lower than that in the WT-SNI group(P<0.01). These results indicated that AQP4 KO inhib- ited activation of spinal astrocytes in SNI model mice. In addition,14 days after SNI surgery,ELISA results showed that the levels of mouse spinal cord proinflammatory cytokines,TNF-α and IL-6 in the WT-SNI group were significantly high- er than those in the WT-Sham group(P<0.05 and P<0.01,respectively),whereas the levels of TNF-α and IL-6 in the KO-SNI group were significantly lower than those in the WT-SNI group(P<0.05 and P<0.01,respectively). These re- sults indicated that AQP4 KO inhibited the level of mouse spinal cord proinflammatory cytokines in SNI model mice. Conclusion: The AQP4 gene knockout may relieve the neuropathic pain via the inhibition of the astrocyte activation and proinflammatory cytokine release.
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There are few studies of infection by rabies virus in the olfactory bulb (OB). This work was carried out with the purpose of establishing the time required to detect rabies antigens in the OB of mouse, after the intramuscular inoculation of the virus and to evaluate the effect of the infection on the expression of three proteins: calbindin (CB), parvalbumin (PV) and the glial fibrillary acidic protein (GFAP). Mice were inoculated with rabies virus intramuscularly in the hind limbs. Every 8 hours, after 72 hours postinoculation (p.i.), animals were sacrificed by perfusion with paraformaldehyde and coronal sections of OB were obtained for immunohistochemical study. These cuts were used to reveal the entry and spread of viral antigens. Tissue sections obtained in the terminal phase of the disease (144 hours p.i.), and controls of the same age were also processed for immunohistochemistry of CB, PV and GFAP. Rabies virus antigens were initially detected at 80 hours p.i. in a few mitral cells. At 88 hours p.i. the antigens had spread through most of these neurons but until the terminal phase of the disease there was little dispersion of the virus towards other cellular layers of the OB. The CB protein was expressed in cells of the glomerular stratum, the PV in cells of the outer plexiform layer and the GFAP was expressed in all the layers of the OB. Viral infection generated loss of CB expression and increase of PV expression. Immunoreactivity to GFAP was increased in the outer plexiform layer of the OB as a response to infection.
Son escasos los estudios de la infección por virus de la rabia en el bulbo olfatorio (OB). Este trabajo se realizó con el objetivo de establecer el tiempo requerido para detectar antígenos de rabia en el OB del ratón, luego de la inoculación intramuscular del virus y evaluar el efecto de la infección en la expresión de tres proteínas: calbindina (CB), parvoalbúmina (PV) y la proteína ácida fibrilar glial (GFAP). Los ratones fueron inoculados con virus de la rabia por vía intramuscular en las extremidades posteriores. Cada 8 horas, después de 72 horas de inoculación (p.i.), los animales se sacrificaron por perfusión con paraformaldehído y se obtuvieron secciones coronales de OB para el estudio inmunohistoquímico. Estos cortes se usaron para revelar la entrada y propagación de antígenos virales. Las secciones de tejido obtenidas en la fase terminal de la enfermedad (144 horas p.i.), y los controles de la misma edad también se procesaron para inmunohistoquímica de CB, PV y GFAP. Los antígenos del virus de la rabia se detectaron inicialmente a las 80 horas p.i. en unas pocas células mitrales. A las 88 horas p.i. los antígenos se habían diseminado a través de la mayoría de estas neuronas, pero hasta la fase terminal de la enfermedad había poca dispersión del virus hacia otras capas celulares del OB. La proteína CB se expresó en las células del estrato glomerular, la PV en células de la capa plexiforme externa y la GFAP se expresó en todas las capas del OB. La infección viral generó pérdida de expresión de CB y aumento en la expresión de PV. La inmunorreactividad a GFAP aumentó en la capa plexiforme externa del OB como respuesta a la infección.
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Animaux , Femelle , Souris , Bulbe olfactif/métabolisme , Bulbe olfactif/virologie , Rage (maladie)/métabolisme , Parvalbumines/métabolisme , Immunohistochimie , Calbindines/métabolisme , Protéine gliofibrillaire acide/métabolismeRésumé
A intoxicação por Tephrosia cinerea causa fibrose hepática periacinar em ovinos na região semiárida do Nordeste, com quadro clínico de ascite acentuada, e, ocasionalmente, com sinais neurológicos. Neste trabalho foram estudadas 16 ovinos em 6 surtos de intoxicação por T. cinerea. Todos os ovinos apresentaram lesões histológicas de fibrose periacinar e seis apresentaram, no encéfalo, vacuolização da substância branca e da junção entre a substância branca e a cinzenta com presença de astrócitos de Alzheimer tipo II na substância cinzenta. A doença foi reproduzida experimentalmente em dois ovinos que apresentaram ascite, desvios vasculares (shunts) porto-sistêmicos e sinais nervosos com lesões histológicas semelhantes a dos casos espontâneos. Na técnica de imuno-histoquímica houve marcação fraca ou ausente do citoplasma astrocitário para o anticorpo anti-GFAP em seis ovinos evidenciando uma alteração degenerativa, em que os astrócitos acumulam corpos densos e reduzem o volume de GFAP. Houve marcação positiva para o anticorpo anti-S100 em oito ovinos, incluindo os dois ovinos experimentais o que sugere reatividade celular, com proliferação mitocondrial e de retículo endoplasmático liso. Estas alterações são caraterísticas dos efeitos da amônia nos astrócitos. Conclui-se que na intoxicação por T. cinerea em alguns ovinos ocorrem sinais nervosos em consequência da encefalopatia hepática.(AU)
In the semiarid region of northeastern Brazil, Tephrosia cinerea causes periacinar hepatic fibrosis in sheep with severe ascites and, occasionally, nervous signs. Sixteen sheep from six outbreaks of T. cinerea poisoning were studied. All sheep had histologic lesion of periacinar fibrosis and six showed, in the brain, vacuolization (spongy degeneration) of the white matter and junction between grey and white matter and presence of Alzheimer type II astrocytes in the grey matter. The disease was produced experimentally in two sheep, that presented porto-sistemic shunts and similar histologic lesions as those observed in the spontaneous cases. Immunohistochemistry revealed weak labelling with anti-GFAP antibodies suggesting a degenerative alteration of astrocytes with accumulation of dense bodies and reduction of the GFAP. There was strong labelling with anti-S100 antibodies suggesting cellular reactivity with proliferation of mitochondria and endoplasmatic reticulum. Such alterations are characteristic of the effects caused by ammonia on the astrocytes. It is concluded that in poisoning by T. cinerea nervous signs due to hepatic encephalopathy occur in some sheep.(AU)
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Animaux , Ovis/physiologie , Encéphalopathie hépatique/médecine vétérinaire , Tephrosia/toxicitéRésumé
Objective·To detect the effects of propofol on rat hippocampal astrocytes and clarify its mechanism.Methods·According to the time after propofol injection,twenty-four SD rats were randomly divided into three groups,i.e.0 min,45 min and 90 min group.Rats were administrated intraperitoneally with propofol (10 mg/mL,100 mg/kg body weight).The levels of glial fibrillary acidic protein (GFAP) and S100β mRNA in rat hippocampus were evaluated by realtime PCR.And cell viabilities and levels of GFAP mRNA were examined in primary cultured hippocampal astrocytes induced by 10 μmol/L propofol with or without 10 μmol/L extracellular signal-regulated kinase (ERK) inhibitor PD98059 pretreatment.Results·The mRNA levels of GFAP in the hippocampal tissue were (1.32±0.12) times (P=0.000) and (1.12±0.09) times (P=0.012) that in 0 min group,respectively,45 min and 90 min after injection of propofol.The mRNA levels of S100β in the hippocampal tissue were (1.14±0.11) times (P=0.005) and (1.05±0.10)times (P=0.284) that in 0 min group,respectively,45 min and 90 min after injection of propofol.The mRNA levels of GFAP and S100β were timedependently altered,first increasing,and then decreasing.In vitro,the cell viabilities (P=0.041) and levels of GFAP mRNA (P=0.026) in primary cultured hippocampal astrocytes were significantly elevated after propofol treatment,and these effects of propofol were reversed by ERK inhibitor PD98059.Conclusion·Propofol time-dependently upregulated the expression of GFAP and S100β via ERK signaling pathway in rat hippocampal astrocytes,so as to activate astrocytes.
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Objective: To detect the effects of propofol on rat hippocampal astrocytes and clarify its mechanism. Methods: According to the time after propofol injection, twenty-four SD rats were randomly divided into three groups, i. e. 0 min, 45 min and 90 min group. Rats were administrated intraperitoneally with propofol (10 mg/mL, 100 mg/kg body weight). The levels of glial fibrillary acidic protein (GFAP) and S100β mRNA in rat hippocampus were evaluated by realtime PCR. And cell viabilities and levels of GFAP mRNA were examined in primary cultured hippocampal astrocytes induced by 10 μmol/L propofol with or without 10 μmol/L extracellular signal-regulated kinase (ERK) inhibitor PD98059 pretreatment. Results: The mRNA levels of GFAP in the hippocampal tissue were (1.32±0.12) times (P=0.000) and (1.12±0.09) times (P=0.012) that in 0 min group, respectively, 45 min and 90 min after injection of propofol. The mRNA levels of S100β in the hippocampal tissue were (1.14±0.11) times (P=0.005) and (1.05±0.10) times (P=0.284) that in 0 min group, respectively, 45 min and 90 min after injection of propofol. The mRNA levels of GFAP and S100β were timedependently altered, first increasing, and then decreasing. In vitro, the cell viabilities (P=0.041) and levels of GFAP mRNA (P=0.026) in primary cultured hippocampal astrocytes were significantly elevated after propofol treatment, and these effects of propofol were reversed by ERK inhibitor PD98059. Conclusion: Propofol time-dependently upregulated the expression of GFAP and S100β via ERK signaling pathway in rat hippocampal astrocytes, so as to activate astrocytes.
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Previous genetic fate-mapping studies have indicated that embryonic glial fibrillary acidic protein-positive (GFAP) cells are multifunctional progenitor/neural stem cells that can produce astrocytes as well as neurons and oligodendrocytes throughout the adult mouse central nervous system (CNS). However, emerging evidence from recent studies indicates that GFAP cells adopt different cell fates and generate different cell types in different regions. Moreover, the fate of GFAP cells in the young adult mouse CNS is not well understood. In the present study, hGFAP-Cre/R26R transgenic mice were used to investigate the lineage of embryonic GFAP cells in the young adult mouse CNS. At postnatal day 21, we found that GFAP cells mainly generated NeuN neurons in the cerebral cortex (both ventral and dorsal), hippocampus, and cerebellum. Strangely, these cells were negative for the Purkinje cell marker calbindin in the cerebellum and the neuronal marker NeuN in the thalamus. Thus, contrary to previous studies, our genetic fate-mapping revealed that the cell fate of embryonic GFAP cells at the young adult stage is significantly different from that at the adult stage.
Sujets)
Animaux , Souris , Astrocytes , Biologie cellulaire , Métabolisme , Encéphale , Biologie cellulaire , Métabolisme , Calbindines , Métabolisme , Protéine gliofibrillaire acide , Métabolisme , Souris transgéniques , Protéines de tissu nerveux , Métabolisme , Cellules souches neurales , Biologie cellulaire , Métabolisme , Neurones , Biologie cellulaire , Métabolisme , Protéines nucléaires , MétabolismeRésumé
OBJECTIVE@#To observe the effects of treatment on the ultrastructure of olfactory bulb and the expression of substantia nigra glial fibrillary acidic protein (GFAP) in mice with Parkinson's disease (PD) induced by lipopolysaccharide (LPS), and to provide methods and evidence for early prevention and treatment of PD.@*METHODS@#Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method.@*RESULTS@#① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all 0.05). ③ After treatment, the footprint and swimming time in the model group were significantly lower than that in the blank group (both <0.01); the footprint and swimming time in the EA group and medication group were significantly higher than those in the model group (all <0.01).④ After treatment, compared with the blank group, the organelles and ultrastructure of olfactory bulb in the model group were significantly improved; the ultrastructure of olfactory bulb in the EA group was improved compared with that in the model group. ⑤ After treatment, the expression of substantia nigra GFAP in the model group was significantly higher than that in the blank group (<0.01); the expression of substantia nigra GFAP in the EA group and medication group was significantly lower than that in the model group (both <0.05).@*CONCLUSION@#The early treatment of can improve behavioral disorders in LPS-induced early PD mice, and the mechanism may be related to the regulation of olfactory disorders and the expression of GFAP in substantia nigra.