Mesenchymal Stem Cell Transplantation Promotes Functional Recovery through MMP2/STAT3 Related Astrogliosis after Spinal Cord Injury

BACKGROUND AND OBJECTIVES: Treatment with mesenchymal stem cells (MSC) in spinal cord injury (SCI) has been highlighted as therapeutic candidate for SCI. Although astrogliosis is a major phenomenon after SCI, the role of astrogliosis is still controversial. In this study, we determined whether acute transplantation of MSC improves the outcome of SCI through modulating astrogliosis. METHODS: Bone marrow derived rat MSCs were induced neural differentiation and transplanted after acute SCI rats. Matrix metalloproteinase (MMP) and neuro-inflammatory pathway were analyzed for acute astrogliosis at 1, 3 and 7 d after SCI in RT-PCR- and western blot analysis. Functional outcome was assessed serially at postoperative 1 d and weekly for 4 weeks. Histopathologic analysis was undertaken at 7 and 28 d following injury in immunohistochemistry. RESULTS: Transplantation of MSCs decreased IL-1α, CXCL-2, CXCL-10, TNF-α and TGF-β in a rat model of contusive SCI. Protein level of NF-κB p65 was slightly decreased while level of STAT-3 was increased. In immunohistochemistry, MSC transplantation increased acute astrogliosis whereas attenuated scar formation with increased sparing white matter of spinal cord lesions. In RT-PCR analysis, mRNA levels of MMP2 was significantly increased in MSC transplanted rats. In BBB locomotor scale, the rats of MSC treated group exhibited improvement of functional recovery. CONCLUSIONS: Transplantation of MSC reduces the inflammatory reaction and modulates astrogliosis via MMP2/STAT3 pathway leading to improve functional recovery after SCI in rats.

Effect of electroacupuncture on reactive astrogliosis of rats with spinal cord injury / 国际中医中药杂志

Objective To study effect of electroacupunture on reactive astrogliosis of rats after spinal cord injury. Methods A total of 36 SD rats were randomly divided into the sham group, model group and electroacupuncture group, 12 rats in each group. The sham group only underwent laminectomy without spinal cord injury, and the impactor was used to establish spinal cord injury model in model group and electroacupuncture group. The electroacupuncture group was given electroacupuncture after operation, while the rest groups were given the same condition of grabing. The Basso Beattie Bresnahan (BBB) scores of rats were recorded daily after operation and rats were sacrificed on the 14th day after administration. Nissl staining was used to observe the morphology of neurons. The expression of GFAP was detected by immunofluorescence. The expression of GFAP protein was detected by Western blot. Results The fifth days after the intervention, the BBB score of the electroacupuncture group was significantly higher than that of the model group (P<0.05). Compared with the model group, the expression of GFAP in electroacupuncture group significantly decreased (F=23.831, P<0.001), the expression of GFAP protein in electroacupuncture group significantly decreased (F=15.883, P<0.001), the expression of IL-1β and TNF-α in electroacupuncture group significantly decreased (F=82.773, 113.487, P<0.001). Conclusions The electroacupuncture can inhibit the expression GFAP and astrogliosis to inhibit inflamation after spinal cord injury in rats, which is conducive to the repair of neurons and the recovery of limb motor function in rats.

Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves Functional Recovery after Spinal Cord Injury

OBJECTIVE: To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. METHODS: Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. RESULTS: The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p < 0.05). The co-immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p < 0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p < 0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p < 0.05). CONCLUSION: These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties.

Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves Functional Recovery after Spinal Cord Injury

OBJECTIVE: To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model.METHODS: Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation.RESULTS: The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p < 0.05). The co-immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p < 0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p < 0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p < 0.05).CONCLUSION: These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties.

Forma esporádica de enfermedad de Creutzfeldt-Jakob: reporte dedos casos / Sporadic Creutzfeldt-Jakob disease: two case reports

La enfermedad de Creutzfeldt-Jakob es la encefalopatía espongiforme más común en el ser humano y prototipode las patologías causadas por priones. Se caracteriza histológicamente por astrogliosis y degeneración dela sustancia gris. Típicamente inicia con síntomas prodrómicos no específicos progresando a demencia conmioclonias y ataxia. Presentamos dos casos de mujeres en edad media con deterioro cognitivo progresivo,dificultades motrices, alteraciones del lenguaje y mioclonias que conducen a la muerte. En electroencefalogramasde ondas trifásicas lentas periódicas así como elevación de proteínas tau y 14-3-3 en LCR por apoyodel The National Prion Disease Pathology Surveillance Center - Cleveland, todos estos hallazgos definen lascondiciones para el diagnóstico clínico de enfermedad por priones. El diagnóstico diferencial en el contextode demencia rápidamente progresiva es amplio, incluyendo infecciones, intoxicaciones, trastornos metabólicos,autoinmunidad, vasculopatías y neoplasias que podrían explicar un posible subregistro en las estadísticasregionales. Existe una posible asociación de riesgo entre enfermedad por priones y médicos patólogos que,aunque discutida, podría limitar el estudio de los especímenes histológicos que son la clave del diagnósticodefinitivo. A pesar de la importancia en salud pública de estas condiciones, el actual modelo de salud limita elmanejo integral de los pacientes.

Creutzfeldt-Jakob is the most common spongiform encephalopathy in humans and the prototype of prions diseases. Astrogliosis and degeneration of the gray matter are the histological features. Typically starts with nonspecific prodromal symptoms that progressing to dementia with myoclonus and ataxia. We present two cases of women in middle age with progressive cognitive impairment, motor difficulties, language disorders and myoclonus that lead to death. EEG slow periodic triphasic waves and elevated protein tau and CSF14-3-3 support for The National Prion Disease Pathology Surveillance Center - Cleveland, all these findings define the conditions for the clinical diagnosis of prion disease. The differential diagnosis in the context of rapidly progressive dementia is broad including infections, poisoning, metabolic disorders, autoimmunity, vascular disease and neoplasms that could explain a possible underreporting in regional statistics. There is a possible risk association between disease and Medical Pathologists that although discussed could limit the study of histological specimens that are key to definitive diagnosis. Despite the public health importance of these conditions the current model of health limits the comprehensive management of patients.

Absence of Delayed Neuronal Death in ATP-Injected Brain: Possible Roles of Astrogliosis

Although secondary delayed neuronal death has been considered as a therapeutic target to minimize brain damage induced by several injuries, delayed neuronal death does not occur always. In this study, we investigated possible mechanisms that prevent delayed neuronal death in the ATP-injected substantia nigra (SN) and cortex, where delayed neuronal death does not occur. In both the SN and cortex, ATP rapidly induced death of the neurons and astrocytes in the injection core area within 3 h, and the astrocytes in the penumbra region became hypertropic and rapidly surrounded the damaged areas. It was observed that the neurons survived for up to 1-3 months in the area where the astrocytes became hypertropic. The damaged areas of astrocytes gradually reduced at 3 days, 7 days, and 1-3 months. Astrocyte proliferation was detectable at 3-7 days, and vimentin was expressed in astrocytes that surrounded and/or protruded into the damaged sites. The NeuN-positive cells also reappeared in the injury sites where astrocytes reappeared. Taken together, these results suggest that astroycte survival and/or gliosis in the injured brain may be critical for neuronal survival and may prevent delayed neuronal death in the injured brain.

Morphological Analysis of Short and Long Term Changes after Ligation of Unilateral Common Carotid Artery in Gerbils

BACKGROUND: The ligation of the unilateral common carotid artery (CCA) in the gerbil has been known as an ischemic animal model showing various changes including selective neuronal necrosis as well as infarction. This study was performed to analyze the short and long term morphological changes of transient unilateral forebrain ischemia with special attention to astroglial proliferation. METHODS: 67 mongolian gerbils were subjected to 2 hr, 3 hr, 4 hr, or 5 hr of forebrain ischemia by the unilateral CCA ligation method. Each of the ischemic groups were examined after a 1 day, 3 day, or 7 day period of reperfusion. Long term reperfusion groups consisted of 2, 3, and 4 weeks of reperfusion after 5hr of unilateral CCA ligation. Morphological changes were analyzed by H-E staining and an immunohistochemical reaction with GFAP antibody. RESULTS: The ligation of the unilateral CCA, induced unilateral hemispheric infarction in 14 gerbils, selective neuronal necrosis (SNN) involving caudate in 1 gerbil, and delayed neuronal necrosis (DND) of the hippocampal CA1 neurons in 2 gerbils. Infarction was most frequent in 1 day reperfusion groups and did not show any differences according to the duration of ischemia. The GFAP reaction was strongly positive in the center of infarction at a 1 day period and negative at a 3 & 7 day period. The surrounding brain parenchyme progressively revealed increased positive reactions. Gerbils with SNN and DND showed moderately or markedly increased GFAP positive reactions in the unilateral caudate, thalamus, and hippocampus, whereas no apparent changes were shown by a H-E stain. CONCLUSIONS: Reactive astrogliosis is a stereotyped reaction of ischemic brain injury and is a more sensitive parameter than neuronal changes.