RESUMEN
Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.
Asunto(s)
Neuropatías Diabéticas/fisiopatología , Giro del Cíngulo/fisiopatología , Hiperalgesia/fisiopatología , Proteínas Represoras/metabolismo , Animales , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/metabolismo , Técnicas de Silenciamiento del Gen , Giro del Cíngulo/metabolismo , Hiperalgesia/complicaciones , Hiperalgesia/genética , Hiperalgesia/metabolismo , Masculino , Ratones , Células PC12 , Ratas , Proteínas Represoras/genética , Regulación hacia ArribaRESUMEN
The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats. Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO), and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion. Infarct volume was calculated by cresyl violet staining. The improvements of neural functions were assessed by behavioral tests. Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs. The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats, and improved neural functional restoration when assessed by rotarod, footfault and corner-turn tests. The grafted cells migrated predominantly to several specific brain regions, such as corpus callosum and peri-infarct area. Furthermore, these cells differentiated into oligodendrocytes and astrocytes in corpus callosum, and neurons in peri-infarct parenchyma. These results suggest that transplanted hNSCs through lateral ventricle of the ischemic side may exert effective therapeutic effects on stroke rats via migration and differentiation in specific brain regions.
Asunto(s)
Animales , Humanos , Ratas , Astrocitos , Biología Celular , Encéfalo , Biología Celular , Patología , Diferenciación Celular , Movimiento Celular , Infarto de la Arteria Cerebral Media , Terapéutica , Ventrículos Laterales , Células-Madre Neurales , Trasplante , Neuronas , Biología Celular , Oligodendroglía , Biología Celular , Ratas Sprague-DawleyRESUMEN
This work was performed to determine the role of delta-opioid receptor (DOR) in protection against acute ischemia/reperfusion injury. Transient (1 h) focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (30 nmol, 60 nmol, 200 nmol), DOR antagonist naltrindole (20 nmol, 50 nmol, 100 nmol) or artificial cerebral spinal fluid (aCSF) was injected respectively into the lateral cerebroventricle of the rat 30 min before the induction of brain ischemia. Neurological deficits were assessed by the five-grade system (Longa's methods). The brain infarct was measured by cresyl violet (CV) staining and infarct volume was analyzed by an image processing and analysis system. The expression of DOR was detected by Western blot. The results showed that 60 nmol TAN-67 significantly reduced the infarct volume (P<0.05), attenuated neurological deficits (P<0.05) and tended to increase the expression of about 60 kDa DOR protein (P>0.05), while 100 nmol naltrindole aggravated ischemic damage and decreased about 60 kDa DOR protein expression (P<0.05). These results suggest that DOR activation protects the brain against acute ischemia/reperfusion injury in rat.
Asunto(s)
Animales , Ratas , Encéfalo , Patología , Isquemia Encefálica , Quimioterapia , Infarto de la Arteria Cerebral Media , Inyecciones Intraventriculares , Naltrexona , Farmacología , Quinolinas , Farmacología , Ratas Sprague-Dawley , Receptores Opioides delta , Daño por ReperfusiónRESUMEN
Transient cerebral ischemia/reperfusion rat model was adopted, and the method of HE staining, TUNEL staining (TdT-mediated dUTP Nick End Labeling) were used to observe the effect of electroacupuncture (EA) and basic fibroblast growth factor (bFGF) on neuronal death. The results evinced that the combination of EA and bFGF could evidently reduce the neuronal death, including both necrosis and apoptosis, compared with EA or bFGF application alone. It is suggested that bFGF and EA can complement each other and enhance the protective effect following cerebral ischemia.