RESUMEN
Autophagy plays vital roles in the pathophysiology of many central nervous system diseases. Emerging evidence indicates that autophagy has both detrimental and protective effects in ischemic cerebral injury. This study aimed to investigate the temporal pattern of autophagy activation in the white matter of bilateral common carotid artery stenosis (BCAS) mouse model by immunofluorescence and western blotting. The effect of wortmannin, an autophagy inhibitor, against hypoperfusion induced white matter injury (WMI) was studied by immunofluorescence and eight-arm radial maze test. We found that autophagy was initially activated in the white matter 3â¯days after BCAS, and then suppressed by day 10, and was activated again at day 30. Administration of wortmannin during the first three days after BCAS revealed protective effects on axon-glia integrity and against the cognitive injury induced by the chronic hypoperfusion. The results indicated the possible link between autophagy and white matter ischemic damage after chronic cerebral hypoperfusion. Modulation of autophagy in a time course dependent manner may broaden the insight on the treatment of WMI.
Asunto(s)
Autofagia/fisiología , Estenosis Carotídea/fisiopatología , Sustancia Blanca/fisiopatología , Animales , Axones/efectos de los fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Estenosis Carotídea/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Neuroglía/efectos de los fármacos , Fármacos Neuroprotectores , Wortmanina/farmacologíaRESUMEN
OBJECTIVE: To investigate the effect of electroacupuncture(EA)stimulation of sensitized acupoints on bowel dysfunction in diarrhea-predominant irritable bowel syndrome(D-IBS)rats. METHODS: Fifty SD rats were randomly divided into control, model, EA sensitized acupoint and EA non-sensitized acupoint groups, with 20 rats in the model group and 10 rats in each of the other 3 groups. The D-IBS model was established by chronic restraint stress and intragastric administration of folium sennae (0.3 g/mL, 10 mL/kg), once daily for 2 weeks, followed by two weeks' restraint stress stimulation. The sensitized acupoints were determined by locating the extravasation points of Evans Blue (EB) dye after tail-intravenous injection, and stimulated with EA (2 mA, 2 Hz) for 30 min, once daily for 7 consecutive days. For rats of the EA non-sensitized acupoint group, bilateral BL 15 were stimulated with the same parameters and same stimulation duration. The rats' bowel mobility was evaluated by Bristol stool scale (BSS), loose stools rate and diarrhea index. RESULTS: After modeling, the BSS, loose stool rate, and diarrhea index were significantly increased in the model group relevant to the control group (P<0.05). After the treatment, the BSS, loose stool rate, and diarrhea index on day 7 were considerably lowered in the EA-BL 25 group (P<0.05) but not in EA-BL15 group (P<0.05), suggesting a better therapeutic effect of EA of the sensitized acupoint. No significant changes were found in the abovementioned 3 indexes on day 4 after the treatment relevant to the model group (P<0.05). CONCLUSIONS: EA stimulation of the sensitized acupoint can improve diarrhea in D-IBS rats.