ABSTRACT
There is debate on the role of glial fibrillary acidic protein (GFAP) as a reliable biomarker in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), and its potential to reflect disease progression. This review aimed to investigate the role of GFAP in MS and NMOSD. A systematic search of electronic databases, including PubMed, Embase, Scopus, and Web of Sciences, was conducted up to 20 December 2023 to identify studies that measured GFAP levels in people with MS (PwMS) and people with NMOSD (PwNMOSD). R software version 4.3.3. with the random-effect model was used to pool the effect size with its 95% confidence interval (CI). Of 4109 studies, 49 studies met our inclusion criteria encompassing 3491 PwMS, 849 PwNMOSD, and 1046 healthy controls (HCs). The analyses indicated that the cerebrospinal fluid level of GFAP (cGFAP) and serum level of GFAP (sGFAP) were significantly higher in PwMS than HCs (SMD = 0.7, 95% CI: 0.54 to 0.86, p < 0.001, I2 = 29%, and SMD = 0.54, 95% CI: 0.1 to 0.99, p = 0.02, I2 = 90%, respectively). The sGFAP was significantly higher in PwNMOSD than in HCs (SMD = 0.9, 95% CI: 0.73 to 1.07, p < 0.001, I2 = 10%). Among PwMS, the Expanded Disability Status Scale (EDSS) exhibited significant correlations with cGFAP (r = 0.43, 95% CI: 0.26 to 0.59, p < 0.001, I2 = 91%) and sGFAP (r = 0.36, 95% CI: 0.23 to 0.49, p < 0.001, I2 = 78%). Regarding that GFAP is increased in MS and NMOSD and has correlations with disease features, it can be a potential biomarker in MS and NMOSD and indicate the disease progression and disability in these disorders.
Subject(s)
Biomarkers , Glial Fibrillary Acidic Protein , Multiple Sclerosis , Neuromyelitis Optica , Humans , Neuromyelitis Optica/blood , Neuromyelitis Optica/physiopathology , Neuromyelitis Optica/diagnosis , Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/analysis , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Multiple Sclerosis/blood , Multiple Sclerosis/physiopathology , Biomarkers/blood , Biomarkers/analysis , Disease ProgressionABSTRACT
OBJECTIVES: To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. METHODS: Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. RESULTS: At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). CONCLUSIONS: Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.
Subject(s)
Animals, Newborn , Mesenchymal Stem Cell Transplantation , Rats, Sprague-Dawley , Umbilical Cord , White Matter , Animals , Rats , Humans , Umbilical Cord/cytology , White Matter/pathology , White Matter/metabolism , Glial Fibrillary Acidic Protein/metabolism , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/analysis , Mesenchymal Stem Cells , Myelin Basic Protein/genetics , Myelin Basic Protein/analysis , Myelin Basic Protein/metabolism , Male , Apoptosis , Female , RNA, Messenger/analysis , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Prehospital triage and treatment of patients with acute coma is challenging for rescue services, as the underlying pathological conditions are highly heterogenous. Recently, glial fibrillary acidic protein (GFAP) has been identified as a biomarker of intracranial hemorrhage. The aim of this prospective study was to test whether prehospital GFAP measurements on a point-of-care device have the potential to rapidly differentiate intracranial hemorrhage from other causes of acute coma. METHODS: This study was conducted at the RKH Klinikum Ludwigsburg, a tertiary care hospital in the northern vicinity of Stuttgart, Germany. Patients who were admitted to the emergency department with the prehospital diagnosis of acute coma (Glasgow Coma Scale scores between 3 and 8) were enrolled prospectively. Blood samples were collected in the prehospital phase. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min) shortly after hospital admission. RESULTS: 143 patients were enrolled (mean age 65 ± 20 years, 42.7% female). GFAP plasma concentrations were strongly elevated in patients with intracranial hemorrhage (n = 51) compared to all other coma etiologies (3352 pg/mL [IQR 613-10001] vs. 43 pg/mL [IQR 29-91.25], p < 0.001). When using an optimal cut-off value of 101 pg/mL, sensitivity for identifying intracranial hemorrhage was 94.1% (specificity 78.9%, positive predictive value 71.6%, negative predictive value 95.9%). In-hospital mortality risk was associated with prehospital GFAP values. CONCLUSION: Increased GFAP plasma concentrations in patients with acute coma identify intracranial hemorrhage with high diagnostic accuracy. Prehospital GFAP measurements on a point-of-care platform allow rapid stratification according to the underlying cause of coma by rescue services. This could have major impact on triage and management of these critically ill patients.
Subject(s)
Coma , Glial Fibrillary Acidic Protein , Intracranial Hemorrhages , Point-of-Care Systems , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biomarkers , Coma/diagnosis , Emergency Service, Hospital , Glasgow Coma Scale , Glial Fibrillary Acidic Protein/analysis , Glial Fibrillary Acidic Protein/blood , Glial Fibrillary Acidic Protein/chemistry , Intracranial Hemorrhages/complications , Intracranial Hemorrhages/diagnosis , Prospective StudiesABSTRACT
Numerous efforts have been undertaken to mitigate the Debye screening effect of FET biosensors for achieving higher sensitivity. There are few reports that show sub-femtomolar detection of biomolecules by FET mechanisms but they either suffer from significant background noise or lack robust control. In this aspect, deformed/crumpled graphene has been recently deployed by other researchers for various biomolecule detection like DNA, COVID-19 spike proteins and immunity markers like IL-6 at sub-femtomolar levels. However, the chemical vapor deposition (CVD) approach for graphene fabrication suffers from various surface contamination while the transfer process induces structural defects. In this paper, an alternative fabrication methodology has been proposed where glass substrate has been initially texturized by wet chemical etching through the sacrificial layer of synthesized silver nanoparticles, obtained by annealing of thin silver films leading to solid state dewetting. Graphene has been subsequently deposited by thermal reduction technique from graphene oxide solution. The resulting deformed graphene structure exhibits higher sensor response towards glial fibrillary acidic protein (GFAP) detection with respect to flat graphene owing to the combined effect of reduced Debye screening and higher surface area for receptor immobilization. Additionally, another interesting aspect of the reported work lies in the biomolecule capture by dielectrophoretic (DEP) transport on the crests of the convex surfaces of graphene in a coplanar gated topology structure which has resulted in 10 aM and 28 aM detection limits of GFAP in buffer and undiluted plasma respectively, within 15 min of application of analyte. The detection limit in buffer is almost four decades lower than that documented for GFAP using biosensors which is is expected to pave way for advancing graphene FET based sensors towards ultrasensitive point-of-care diagnosis of GFAP, a biomarker for traumatic brain injury.
Subject(s)
Biosensing Techniques , Glial Fibrillary Acidic Protein , Graphite , Humans , Biosensing Techniques/methods , Electrophoresis/methods , Glass/chemistry , Glial Fibrillary Acidic Protein/analysis , Graphite/chemistry , Limit of Detection , Metal Nanoparticles/chemistry , Silver/chemistry , Transistors, ElectronicABSTRACT
SUMMARY: The microstructure of inner ear in Scincella tsinlingensis was observed by light microscopy and the expression of glial fibrillary acidic protein (GFAP) in membranous labyrinth among the juvenile age group, subadult age group and adult age group were also detected by methods of immunohistochemistry. The inner ear in S. tsinlingensis resembled those in other Scincid lizards in their anatomy and histology. Large and elongate cochlear duct was slightly bowed or arched laterally. There was no hint of limbic modifications and the limbic lip was absent in cochlear recess. The basilar papilla elongated anteroventrally possessed specialized tectorial sallets. GFAP staining was significantly distributed in supporting cells of the sensory epithelia of cochlear duct, while the utricular macula and canal ampullae showed immunopositive for the GFAP antibody, with weaker staining in the saccular macula. The membranous inner ear of three different age groups revealed the similar pattern of GFAP expression, which suggested that the distribution of supporting cells were independent of age in S. tsinlingensis.
RESUMEN: La microestructura del oído interno en Scincella tsinlingensis fue analizada mediante microscopía óptica y por otra parte, fue cuantificada la expresión de la proteína ácida fibrilar glial (GFAP) en el laberinto membranoso, entre los grupos de edad juvenil, subadulto y adulto, utilizándose métodos inmunohistoquímicos. El oído interno de S. tsinlingensis se asemejaba al de otros lagartos Scincid tanto en su anatomía como en su histología. El conducto coclear mayor estaba ligeramente arqueado o arqueado lateralmente. No había indicios de modificaciones límbicas y no se evidenció el labio en el receso coclear. La papila basilar alargada anteroventralmente poseía sallets tectoriales especializados. La tinción de GFAP se distribuyó significativamente en las células del epitelio sensorial del conducto coclear, mientras que la mácula utricular y la ampolla del canal mostraron inmunopositividad para el anticuerpo GFAP, con una tinción más débil en la mácula sacular. El oído interno membranoso de los tres grupos de edad diferentes reveló un patrón similar de expresión de GFAP, lo que sugiere que la distribución de las células de soporte son independiente de la edad en S. tsinlingensis.
Subject(s)
Animals , Glial Fibrillary Acidic Protein/metabolism , Ear, Inner/anatomy & histology , Lizards/anatomy & histology , Immunohistochemistry , Glial Fibrillary Acidic Protein/analysis , Ear, Inner/chemistry , MicroscopyABSTRACT
Abstract Purpose To investigate the role of Rosmarinic acid (RA) in the prevention of traumatic brain injury and the immunohistochemical analysis of IBA-1 and GFAP expressions. Methods Healthy male rats were randomly divided into 3 groups consisting of 10 rats. Groups were as follows; control group, traumatic brain injury (TBI) group, and TBI+RA group. After traumatic brain injury, blood samples were taken from the animals and analyzed with various biochemical markers. And then IBA-1 and GFAP expressions were evaluated immunohistochemically. Results Significant results were obtained in all biochemical parameters between groups. Immunohistochemical sections showed IBA-1 not only in microglia and macrophage activity but also in degenerative neurons in blood vessel endothelial cells. However, GFAP reaction and post-traumatic rosmarinic acid administration showed positive expression in astrocytes with regular structure around the blood vessel. Conclusion Rosmarinic acid in blood vessel endothelial cells showed that preserving the integrity of astrocytic structure in the blood brain barrier may be an important antioxidant.
Subject(s)
Animals , Male , Calcium-Binding Proteins/analysis , Cinnamates/pharmacology , Craniotomy/methods , Depsides/pharmacology , Brain Injuries, Traumatic/prevention & control , Glial Fibrillary Acidic Protein/analysis , Microfilament Proteins/analysis , Reference Values , Immunohistochemistry , Random Allocation , Astrocytes/drug effects , Reproducibility of Results , Rats, Sprague-Dawley , Neuroprotective Agents/pharmacology , Brain Injuries, Traumatic/surgery , Brain Injuries, Traumatic/pathology , Glutathione Peroxidase/analysis , Malondialdehyde/analysisABSTRACT
ABSTRACT Objective: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. Methods: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. Results: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. Conclusion: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.
RESUMO Objetivo: A inflamação hipotalâmica e a superexpressão da proteína glial fibrilar ácida (GFAP) em astrócitos são bem descritas em animais obesos, assim como déficits cognitivos e de memória. Como o hipocampo desempenha importante papel na consolidação de informações, esta investigação teve como objetivo observar a função da memória e a expressão astrocitária da GFAP no hipocampo de ratos que receberam dieta hipercalórica ou normocalórica. Métodos: Ratos Wistar machos adultos receberam dieta rica em gordura (cafeteria) ou dieta padrão por 60 dias. No 61º dia, os ratos foram submetidos ao teste de reconhecimento de objetos (NOR) 3 e 24 horas após o primeiro contato com os objetos, para avaliação da memória de curto e de longo prazo, respectivamente. Após, os ratos foram eutanasiados e os encéfalos coletados para pesquisa imuno-histoquímica da expressão astrocitária de GFAP no hipocampo (áreas CA1, CA2 e CA3) e no hipotálamo (núcleos periventricular e arqueado). A reatividade astrocitária foi avaliada por morfometria. Diferentes depósitos de tecido adiposo branco e marrom foram pesados para calcular o índice de adiposidade. Resultados: A dieta hipercalórica aumentou o ganho de peso corporal, o índice de adiposidade, o peso do tecido adiposo branco (epididimal, subcutâneo e retroperitoneal) e marrom. Ratos alimentados com dieta hipercalórica apresentaram prejuízos na memória de curto e longo prazo no teste NOR e aumento da expressão de GFAP em astrócitos de todas as áreas hipotalâmicas e hipocampais analisadas. Conclusão: Esta astrogliose sugere que a resposta neuroinflamatória também ocorre no hipocampo, podendo estar envolvida nas perdas de memória observadas em animais obesos/com sobrepeso.
Subject(s)
Animals , Male , Astrocytes/chemistry , Diet, High-Fat/adverse effects , Glial Fibrillary Acidic Protein/analysis , Hippocampus/cytology , Memory Disorders/etiology , Obesity/complications , Reference Values , Time Factors , Immunohistochemistry , Adipose Tissue/metabolism , Rats, Wistar , Glial Fibrillary Acidic Protein/metabolism , Memory Disorders/metabolism , Obesity/metabolismABSTRACT
ABSTRACT Obesity is associated with a chronic and low-grade inflammatory response in the hypothalamus, where astrogliosis occurs with the upregulation of the astrocyte structural protein GFAP. As propentofylline (PPF) has inhibitory effects on astrocyte and microglial activation during inflammation, this study aimed to investigate if this xanthine derivative could decrease the astrocyte reaction induced by a hypercaloric diet (HD). Male Wistar rats were divided into four groups: NDS - rats receiving a normocaloric diet (ND) and daily saline solution; NDP - rats receiving ND and daily PPF (12.5 mg/kg/day, intraperitoneal route); HDS - rats receiving HD and saline solution, HDP - rats receiving HD and PPF. On the 21st day, rats were anesthetized, and perfused, and brains were collected for GFAP immunohistochemical study in the hypothalamus. Results showed that HD induced increased weight gain and hypothalamic astrogliosis. Propentofylline decreased the expression of GFAP in the HDP group, although it did not affect the weight gain induced by this diet.
RESUMO A obesidade está associada com uma resposta inflamatória crônica e de baixo grau no hipotálamo, onde ocorre astrogliose com a superexpressão da proteína astrocitária GFAP. Como a propentofilina (PPF) possui efeitos inibitórios sobre a ativação astrocitária e microglial durante a inflamação, este estudo visou a investigar se esta xantina podia diminuir a reação astrocitária induzida pela dieta hipercalórica (HD). Ratos Wistar machos foram divididos em 4 grupos: NDS- ratos recebendo dieta normocalórica (ND) e solução salina diária; NDP- ratos recebendo ND e PPF diária (12.5 mg/kg/dia, via intraperitoneal); HDS- ratos recebendo HD e solução salina, HDP- ratos recebendo HD e PPF. No 21° dia, os ratos foram perfundidos e os encéfalos, coletados para estudo imuno-histoquímico para a GFAP no hipotálamo. Os resultados mostram que a HD induziu aumento do ganho de peso e astrogliose no hipotálamo. A PPF diminuiu a expressão de GFAP no grupo HD, embora não tenha afetado o ganho de peso induzido por esta dieta.
Subject(s)
Animals , Male , Rats , Xanthines/administration & dosage , Diet, High-Fat/adverse effects , Glial Fibrillary Acidic Protein/analysis , Gliosis/etiology , Hypothalamic Diseases/etiology , Rats, Wistar , Gliosis/prevention & control , Hypothalamic Diseases/prevention & controlABSTRACT
ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorphï software and serum levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1ß decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo
Subject(s)
Animals , Male , Rats , Glial Fibrillary Acidic Protein/analysis , Analgesics/pharmacology , Pain/drug therapy , Astrocytes/immunology , Cytokines/classificationABSTRACT
ABSTRACT Propentofylline is a xanthine derivative that depresses activation of glial cells, whose responses contribute to neural tissue damage during inflammation. Ethidium bromide injection into the central nervous system induces local oligodendroglial and astrocytic loss, resulting in primary demyelination, neuroinflammation and blood-brain barrier disruption. Surviving astrocytes present a vigorous reaction around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). Objective This study aimed to evaluate the effect of propentofylline administration on astrocytic response following gliotoxic injury. Method Wistar rats were injected with ethidium bromide into the cisterna pontis and treated or not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from 15 to 31 days after gliotoxic injection and processed for GFAP immunohistochemistry. Results and Conclusion Results demonstrate that propentofylline decreased astrocytic activation until the 21st day, suggesting that this drug may have a role in reducing glial scar development following injury.
RESUMO A propentofilina é uma xantina que deprime a ativação das células gliais, cujas respostas contribuem para o dano neural durante inflamação. A injeção de brometo de etídio no sistema nervoso central induz a perda oligodendroglial e astrocitária, resultando em desmielinização, neuroinflamação e ruptura da barreira hematoencefálica. Os astrócitos sobreviventes apresentam vigorosa reação ao redor da lesão com aumento da imunorreatividade à proteína glial fibrilar ácida (GFAP). Objetivo Este estudo objetivou avaliar o efeito da propentofilina sobre a resposta astrocitária após injúria gliotóxica. Método Ratos Wistar foram injetados com brometo de etídio na cisterna basal e tratados ou não com propentofilina (12.5mg/kg/dia, intraperitoneal). Amostras do tronco encefálico foram coletadas dos 15 aos 31 dias pós-injeção do gliotóxico e processadas para estudo ultraestrutural e imuno-histoquímico para GFAP. Resultados e Conclusão Os resultados demonstram que a propentofilina reduziu a ativação astrocitária até o 21o dia, sugerindo que essa droga pode atuar na redução da cicatriz glial após injúria.
Subject(s)
Animals , Male , Xanthines/pharmacology , Brain Stem/drug effects , Astrocytes/drug effects , Neuroprotective Agents/pharmacology , Time Factors , Brain Stem/metabolism , Immunohistochemistry , Astrocytes/metabolism , Reproducibility of Results , Demyelinating Diseases/metabolism , Demyelinating Diseases/prevention & control , Treatment Outcome , Rats, Wistar , Disease Models, Animal , Ethidium/toxicity , Glial Fibrillary Acidic Protein/analysis , Glial Fibrillary Acidic Protein/drug effects , Gliotoxin/toxicityABSTRACT
Introducción. El accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, y más de 85 % es de origen isquémico. Objetivo. Evaluar en un modelo de infarto cerebral por embolia arterial el efecto de la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, sobre la respuesta neuronal, los astrocitos y la microglia. Materiales y métodos. Se sometieron ratas Wistar a embolia de la arteria carótida y a tratamiento con meloxicam y atorvastatina, administrados por separado y conjuntamente, a las 6, 24, 48 y 72 horas. Se evaluó la reacción de las proteínas COX-2, GFAP y OX-42 en las neuronas, los astrocitos y la microglia mediante inmunohistoquímica y estudios morfológicos y de densitometría. Los datos obtenidos se evaluaron por medio de un análisis de varianza y de pruebas no paramétricas de comparación múltiple. Resultados. La isquemia cerebral por embolia arterial incrementó significativamente (p<0,001) la reacción de los astrocitos y la microglia, en tanto que la atorvastatina y el meloxicam, administrados por separado y de forma conjunta, la redujeron. La isquemia produjo acortamiento de las proyecciones de los astrocitos, engrosamiento celular, ruptura de las expansiones protoplásmicas (clasmatodendrosis) y cambios morfológicos en la microglia propios de diversas etapas de actividad. En las zonas circundantes del foco se incrementó la reacción inmunológica de la COX-2 y se redujo en el foco isquémico, en tanto que el meloxicam y la atorvastatina redujeron significativamente (p<0,001) la reacción inmunológica en la zona circundante del foco, restableciendo la marcación de la ciclooxigenasa en el foco isquémico. Conclusión. La combinación de meloxicam y atorvastatina atenúa la respuesta de los astrocitos y la microglia en el proceso inflamatorio posterior a la isquemia cerebral por embolia arterial, reduciendo la degeneración neuronal y restableciendo el equilibrio morfológico y funcional del tejido nervioso.
Introduction: Stroke is the second leading cause of death and the first cause of disability in the world, with more than 85% of the cases having ischemic origin. Objective: To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Materials and methods: Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin at 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Data were evaluated by variance analysis and non-parametric multiple comparison. Results: Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p<0.001), whereas it was reduced by atorvastatin, meloxicam and their association. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various activity stages. In perifocal areas, immunoreactivity of COX-2 was increased and in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p<0.001) perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. Conclusion: These results suggest that the meloxicam-atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring the morphological and functional balance of nervous tissue .
Subject(s)
Animals , Female , Rats , Brain Ischemia/drug therapy , Cyclooxygenase Inhibitors/therapeutic use , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intracranial Embolism/complications , Nerve Degeneration/prevention & control , Pyrroles/therapeutic use , Thiazines/therapeutic use , Thiazoles/therapeutic use , Atorvastatin , /analysis , Astrocytes/drug effects , Astrocytes/pathology , Biomarkers , Brain Ischemia/etiology , Brain Ischemia/pathology , Carotid Stenosis/complications , Carotid Stenosis/pathology , Cyclooxygenase Inhibitors/administration & dosage , Disease Models, Animal , Drug Evaluation, Preclinical , Glial Fibrillary Acidic Protein/analysis , Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Inflammation , Intracranial Embolism/pathology , Microglia/drug effects , Microglia/pathology , Nerve Tissue Proteins/analysis , Pyrroles/administration & dosage , Random Allocation , Rats, Wistar , Thiazines/administration & dosage , Thiazoles/administration & dosageABSTRACT
OBJETIVO: Avaliar a expressão da Proteína Acídica Fibrilar Glial após a injúria por isquemia-reperfusão. MÉTODOS: vinte e quatro ratos foram distribuídos em quatro grupos: Controle, submetidos à anestesia e biópsia hepática; Simulação, injeção de heparina através da veia cava e dissecção do pedículo hepático superior, biópsia após 24 horas; Isquemia 30 minutos, mesmo procedimento do grupo Simulação, acrescido de clampeamento do pedículo hepático superior por 30 minutos; Isquemia 90 minutos, mesmo procedimento do grupo Isquemia 30 minutos, porém com período de clampeamento de 90 minutos. Após 24 horas de observação, os animais foram submetidos à laparotomia e seus fígados avaliados macroscopicamente, microscopicamente, por coloração de Hematoxilina-Eosina (HE) e submetidos à análise da expressão da GFAP por Western Blotting. RESULTADOS: Não se observou diferença no aspecto macroscópico dos fígados entre os diferentes grupos experimentais, tendo todos evidenciado morfologia normal. A análise por HE não evidenciou diferenças significativas, no que diz respeito à morfologia lobular. Por outro lado, nos grupos isquemia, foram encontrados infiltrados neutrofílicos e pequenas áreas de necrose. A expressão de GFAP foi semelhante em todos os grupos, seja qualitativamente quanto quantitativamente. CONCLUSÃO: A expressão da Proteína Acídica Fibrilar Glial não se alterou em nosso modelo de isquemia-reperfusão.
OBJECTIVE: To evaluate the expression of Glial Fibrillary Acidic Protein (GFAP) after ischemia-reperfusion injury. METHODS: twenty four rats were divided into four groups: Control, submitted to anesthesia and liver biopsy; Sham, receiving injection of heparin through the vena cava and hepatic pedicle dissection, with liver biopsy after 24 hours; Ischemia-30, the same as Sham group, plus hepatic pedicle clamping for 30 minutes; and Ischemia-90, the same procedure of Ischemia-30 group, but with clamping period of 90 minutes. After 24 hours of observation, the animals underwent laparotomy and we evaluated their livers macroscopically, microscopically by hematoxylin-eosin (HE) and analyzed the expression of GFAP by Western Blotting. RESULTS: There was no difference in the gross appearance of the livers between the different experimental groups, all having demonstrated normal morphology. HE analysis showed no significant differences with respect to lobule morphology. On the other hand, in the ischemia groups we observed neutrophilic infiltrates and small areas of necrosis. GFAP expression was similar in all groups, either qualitatively and quantitatively. CONCLUSION: The expression of Glial Fibrillary Acidic Protein did not change in our model of ischemia-reperfusion.
Subject(s)
Animals , Rats , Glial Fibrillary Acidic Protein/biosynthesis , Liver/blood supply , Reperfusion Injury/metabolism , Biomarkers/analysis , Glial Fibrillary Acidic Protein/analysis , Liver/chemistry , Rats, WistarABSTRACT
Gliomatosis cerebri (GC) is a rare form of CNS neoplasia in which there is diffuse involvement of the nervous tissue with or without the presence of tumor mass. The origin of the tumor is unknown, nor whether it represents a disease with diffuse onset or infiltration from a neoplastic focus. Here we studied the histopathologic characteristics of 6 cases with a diagnosis of GC and performed an immunohistochemical analysis using glial fibrillary acidic protein (GFAP), synaptophysin, nestin and vimentin. Most tumor cells were negative for GFAP, even though there were foci of positivity for this marker in all cases. We detected the presence of many positive cells for nestin and vimentin in all studied samples. The presence of these cells may indicate origin of the tumor from undifferentiated cells with a high degree of mobility.
A gliomatosis cerebri (GC) é uma forma rara de neoplasia do sistema nervoso central em que existe o envolvimento difuso do tecido nervoso com ou sem a presença de massa tumoral. A origem do tumor é incerta, bem como se representa uma doença de início difuso ou uma infiltração a partir de um foco de neoplasia. Foram estudadas as características histopatológicas de seis casos com diagnóstico de GC e realizada imuno-histoquímica utilizando-se GFAP, sinaptofisina, nestina e vimentina. A maioria das células tumorais mostrou-se negativa para GFAP, apesar de existirem focos de positividade para este marcador em todos os casos. Observamos muitas células positivas para nestina e para vimentina em todas as amostras estudadas. Estas células poderiam indicar a origem do tumor em células multipotenciais com alto grau de mobilidade.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Astrocytoma/metabolism , Brain Neoplasms/metabolism , Intermediate Filament Proteins/analysis , Nerve Tissue Proteins/analysis , Biomarkers, Tumor/analysis , Vimentin/analysis , Astrocytoma/pathology , Brain Neoplasms/pathology , Glial Fibrillary Acidic Protein/analysis , Immunohistochemistry , Magnetic Resonance Imaging , Synaptophysin/analysis , Tomography, X-Ray ComputedABSTRACT
El adenoma de células basales es un tipo específico de adenomacon una apariencia histológica uniforme y monomorfa, en el que predominanlas células basaliodes sin el componente mixocondroide del tumormixto. Atendiendo a su morfología pueden ser divididos en cuatro subtipos:sólido, tubular, trabecular y membranoso.Presentamos cuatro casos de adenoma de células basales localizados englándula parótida: uno de tipo sólido, uno de tipo trabecular y dos de tipomembranoso, tratados mediante parotidectomía superficial conservadoraen todos los casos.Esta división en distintos patrones morfológicos tiene una finalidad descriptiva,salvo en el subtipo membranoso por su mayor tendencia a la multifocalidady a la recidiva, su ocasional transformación maligna, así comopor su posible asociación en un tercio de los casos a tumores ecrinos dermales.Esto implica un seguimiento más estrecho y un despistaje de posibleslesiones cutáneas asociadas
The basal cell adenoma is a specific type of adenoma,with a uniform, monomorphous histologic appearance that isdominated by basaloid cells and that does not have themyxochondroid tissue characteristic of mixed tumors. It may bedivided on the basis of its morphologic pattern into four subtypes:solid, tubular, trabecular and membranous. We report four casesof basal cell adenoma subdivided as follows: one solid, one trabecularand two membranous subtypes. In all cases a conservative superficialparotidectomy was the treatment.Morphologic identification of the specific subtype is for descriptivepurposes, except in the case of the membranous type, due to itstendency to be multifocal, its high recurrence rate, its occasionalmalignant transformation and its possible association in about onethirdof the reported cases with dermal cylindromas. A close followupand screening of skin lesions is suggested for these tumors
Subject(s)
Male , Female , Humans , Stem Cells/pathology , Parotid Neoplasms/pathology , Adenoma/pathology , Eccrine Glands/pathology , Neoplasm Recurrence, Local , Parotid Neoplasms/surgery , Glial Fibrillary Acidic Protein/analysisABSTRACT
The quantitative relationship between glial fibrillary acidic protein (GFAP) hyper-reactivity and -amyloid protein (AP) deposition was investigated by double immunoperoxidase labeling of hippocampal and entorhinal cortex sections from five Alzheimer´s disease (AD) cases and five age-matched controls. AP plaques, which were absent in controls, were found in all AD samples, without significant differences in number or perimeter according to their location among the regions studied. In contrast, the mean number of GFAP (+) cells was significantly greater in the hippocampus than in the entorhinal cortex from AD cases (49 vs.39). Although at lower values (30 vs. 20), predominance of astrocyte hyperplasia in hippocampus as compared with entorhinal cortex was also found in control samples. Concomitant astrocyte hypertrophy, as defined by surface density (Sv) values of GFAP-immunoreactive material exceeding those of control means, affected a similar proportion of cells in the hippocampus (73%) and the entorhinal cortex (74%) from AD cases. Since an increased number of GFAP (+) cells in the hippocampus was not accompanied by an increased number and/or perimeter of neighbouring plaques, such differential hyper-reactivity in samples from AD patients, as well as in those with normal aging, seems to depend partially on the regional location of the involved astrocyte.
Subject(s)
Aged , Humans , Aging/pathology , Alzheimer Disease/pathology , Astrocytes/pathology , Amyloid beta-Peptides/analogs & derivatives , Astrocytes/cytology , Case-Control Studies , Cell Count , Entorhinal Cortex/chemistry , Entorhinal Cortex/pathology , Glial Fibrillary Acidic Protein/analysis , Hippocampus/chemistry , Hippocampus/pathology , ImmunohistochemistryABSTRACT
The quantitative relationship between glial fibrillary acidic protein (GFAP) hyper-reactivity and -amyloid protein (AP) deposition was investigated by double immunoperoxidase labeling of hippocampal and entorhinal cortex sections from five Alzheimer s disease (AD) cases and five age-matched controls. AP plaques, which were absent in controls, were found in all AD samples, without significant differences in number or perimeter according to their location among the regions studied. In contrast, the mean number of GFAP (+) cells was significantly greater in the hippocampus than in the entorhinal cortex from AD cases (49 vs.39). Although at lower values (30 vs. 20), predominance of astrocyte hyperplasia in hippocampus as compared with entorhinal cortex was also found in control samples. Concomitant astrocyte hypertrophy, as defined by surface density (Sv) values of GFAP-immunoreactive material exceeding those of control means, affected a similar proportion of cells in the hippocampus (73%) and the entorhinal cortex (74%) from AD cases. Since an increased number of GFAP (+) cells in the hippocampus was not accompanied by an increased number and/or perimeter of neighbouring plaques, such differential hyper-reactivity in samples from AD patients, as well as in those with normal aging, seems to depend partially on the regional location of the involved astrocyte. (AU)
Subject(s)
Aged , Humans , RESEARCH SUPPORT, NON-U.S. GOVT , Aging/pathology , Alzheimer Disease/pathology , Astrocytes/pathology , Astrocytes/cytology , Glial Fibrillary Acidic Protein/analysis , Amyloid beta-Peptides/analogs & derivatives , Entorhinal Cortex/chemistry , Entorhinal Cortex/pathology , Hippocampus/chemistry , Hippocampus/pathology , Immunohistochemistry , Case-Control Studies , Cell CountABSTRACT
Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.
Subject(s)
Animals , Rats , Analysis of Variance , Apoptosis , Comparative Study , Glial Fibrillary Acidic Protein/analysis , In Situ Nick-End Labeling , Microscopy, Fluorescence , RNA, Messenger/genetics , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord/chemistry , Spinal Cord Injuries/enzymology , Time FactorsABSTRACT
We report a case of cellular schwannoma, a rare benign nerve-sheath tumor in a 27 year-old woman. It was presented as a voluminous lesion in the paraspinal region that caused lumbar vertebral body destruction. These features, in association to the microscopic aspects of a hypercellular, pleomorphic neoplasm may lead to a false impression of a malignant tumor. Therefore, it is important to have an accurate examination to confirm the benign nature of this tumor thus avoiding unnecessary therapy
Subject(s)
Humans , Female , Adult , Nerve Sheath Neoplasms , Neurilemmoma/pathology , Spinal Cord Neoplasms/pathology , Glial Fibrillary Acidic Protein/analysis , Immunohistochemistry , Magnetic Resonance Imaging , Nerve Sheath Neoplasms , /analysis , Spinal Cord Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
The expression of two intermediate filaments, nestin and vimentin, was studied in spinal cord injury (SCI) to elucidate their roles in the formation of glial scars. Rats were sacrificed 1, 4, and 7 days after induction of compression injury of the spinal cord using an aneurysm clip. The affected spinal cords were studied using antibodies against nestin and vimentin intermediate filaments. One day after spinal cord injury, some clusters of nestin-positive vessels were detected in the center of the injury, but few were seen in other cell types. Vimentin immunostaining was detected in some glial cells in the center and its level of immunoreactivity was enhanced in the ependymal cells of the central canal. On days 4 and 7 after spinal cord injury, astrocytes and some ependymal cells in the central canal were stained positively for nestin and increased expression of nestin was observed in vessels. Vimentin was detected in some macrophages and astrocytes in the lesions. Nestin was co-localized with glial fibrillary acidic protein in some glial cells in SCI. These findings imply that spinal cord cells in adult animals have embryonic capacity, and these cells are activated after injury, which in turn contributes to repair of spinal cord injury through formation of a glial scar.
Subject(s)
Animals , Rats , Cicatrix/pathology , Glial Fibrillary Acidic Protein/analysis , Immunohistochemistry , Intermediate Filament Proteins/analysis , Intermediate Filaments/physiology , Nerve Tissue Proteins , Neuroglia/pathology , Rats, Sprague-Dawley , Spinal Cord Injuries/pathology , Vimentin/analysisABSTRACT
The clinicopathological features and immunohistochemistry profile of desmoplastic cerebral astrocytoma of infancy are discussed in a 4 month old male infant who presented with an increasing head circumference more pronounced in the last two weeks prior to admission to the University Pediatric Hospital. This is a rare tumor that occurs in infants within the first two years of life and it is characterized by a massive, often cystic, supratentorial lesion usually in the frontoparietal region. It has a biphasic histologic pattern with an astrocytic and desmoplastic component and a good prognosis after total or near total surgical resection. This patient represents the first case of desmoplastic cerebral astrocytoma of infancy diagnosed in the Puerto Rico Medical Center.