ABSTRACT
Objective To investigate the effect of rapamycin (RAPA) on mitochondrial injury in a mouse model of aging Parkinson's disease (PD).Methods Forty senescence-accelerated prone mice 8 (SAMP8) (12-month old) were randomly divided into 5 groups:blank group,model group,and RAPA low-,middle-,and high-dose groups.Mice in the model group and three RAPA groups were administered a subcutaneous injection of MPTP to generate the PD model.RAPA at 1,2,and 4 mg· kg 1· d 1 was administered from 7 days before,5 days during,and 7 days after the PD model preparation to the RAPA groups;an equal volume of sterile saline was administered to the other two groups.After the administration,behavioral test scores,dopamine levels,transmembrane potential of mitochondria,and activity of mitochondrial complex Ⅰ in the 5 groups were evaluated.Results Behavioral scores,dopamine levels,transmembrane potential,mitochondrial complex Ⅰ activity of mice in the model group were significantly decreased compared with the blank group (P ＜ 0.05 respectively).All indexes in the RAPA groups were significantly improved compared to the model group (P ＜ 0.05 respectively).There was no significant difference among the three RAPA groups.Conclusion RAPA has a protective effect on aging PD model mice,and its mechanism may be related to the protection against mitochondrial damage.
ABSTRACT
Objective To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs)transplantation on the treatment of hypoxic-ischemic encephalopathy(HIE). Methods A total of 25 HIE patients were randomly divided into stem cell transplantation group(15 case)and control group(10 cases). The patients in transplantation group were given intravenous infusion of hUCMSCs,which isolated under sterile condition in vitro and cultured, while in control group were treated with routine drug treatment. Neurological function( American National Institutes of Health Stroke Scale( NIHSS ),Barthel index (BI)),extrapyramidal function(Unified Parkinson's disease questionnaire(UPDRS)),cognition and emotional reaction(The mini mental state examination(MMSE),the 14 item Hamilton Depression Scale(HAMD14)and HAMD24)were all assessed before and after transplantation for 14 d,90 d and 180 d respectively to evaluate the clinical efficacy of hUCMSCs transplantation. Results There was no significant difference between two groups in terms of each function before transplantation. The scores of transplantation group were all obviously improved after treatment for 14 d,90 d and 180 d compared to that of before treatment,and the therapy effect in transplantation group was significantly better than that of the control group( NIHSS:Ftime =4. 372,P=0. 031;Ftime*group =4. 175,P=0. 038;Fgroup =3. 897,P=0. 045.BI:Ftime =4. 728,P=0. 044;Ftime*group =4. 894,P=0. 037;Fgroup =4. 284,P=0. 039.UPDRS:Ftime =5. 112,P=0. 047;Ftime*group =4. 895,P=0. 045;Fgroup=3. 879,P =0. 031.MMSE:Ftime =5. 135,P =0. 039;Ftime*group =3. 213,P =0. 036;Fgroup =4. 184,P=0. 045.HAMD14:Ftime =3. 977,P =0. 049;Ftime*group =4. 587,P =0. 038;Fgroup =4. 381,P =0. 041.HAMD24:Ftime =3. 845,P =0. 033;Ftime*group =4. 125,P=0. 035;Fgroup =3. 547,P=0. 034). Conclusion Transplantation of hUCMSCs is safe and effective for treatment of HIE,which can significantly improve the neurological function,extrapyramidal function,cognition and emotion.
ABSTRACT
Cerebral small vessel disease refers to the diseases that affects intracranial small arteries,arterioles,precapillaries,and venules.The image-based types mainly include white matter lesion,lacunar infarction,and cerebral microbleeds.It is believed to be the independent risk factors of cognitive impairment or vascular dementia.The location,number and volume of the small vessel diseases may all influence the degree of cognitive impairment and manifestation.
ABSTRACT
BACKGROUND:Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine can induce the clinical, biochemical and pathological characteristics similar to those observed in primary Parkinson’s disease. OBJECTIVE:To observe the effects of repetitive transcranial magnetic stimulation on the proliferation of endogenous neural stem cells of Parkinson’s disease model mice and the mood change. METHODS:A total of 72 male C57BL/6J mice were randomly divided into four groups:normal saline group, Parkinson’s disease model group (model group), sham-repetitive transcranial magnetic stimulation group (sham group) and repetitive transcranial magnetic stimulation group. The mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection×4 to establish acute Parkinson’s disease models. The mice in the normal saline group were injected the same volume saline. And 24 hours after the last injection of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine, the mice in the repetitive transcranial magnetic stimulation group received five trains of repetitive transcranial magnetic stimulation, 1 Hz for 25 seconds, at an intensity of 1 Tesla daily for 1, 3, 7 consecutive days. Sham group mice were not exposed to the magnetic field. No treatment was performed in the mice of model group. The mood change was evaluated using the elevated-plus maze testing before and after repetitive transcranial magnetic stimulation treatment. The change in expression of nestin in the subventricular zone was observed by using immunohistochemical technique. RESULTS AND CONCLUSION:(1) Elevated-plus maze testing:There was no statistical significance about percentage of opening arm time accounting for total time among groups and at different time points in each group, but after stimulation, the percentage of opening arm time accounting for total time showed a declined tendency. (2) The results of nestin immunohistochemical staining:Compared to the normal saline group, the number of nestin-positive cells of the model group was increased at days 3 and 7, and there was no statistical significance in the number of nestin-positive cells between model group and sham group;Compared to the sham group and model group, the number of nestin-positive cells of repetitive transcranial magnetic stimulation group were evidently increased;The proliferation of endogenous neural stem cells was time-dependent, endogenous neural stem cells exhibited outward migration gradual y along the certain way, and some cells were able to migrate to the corpus cal osum at day 3, and even to the cerebral cortex at day 7. Repetitive transcranial magnetic stimulation can promote the endogenous neural stem cells in a time-depended manner.
ABSTRACT
Objective To investigate the effect of acetyl-L-carnitine (ALC) preconditioning on the PC12 cell apoptosis induced by oxygen-glucose deprivation.Methods PC12 cells were seeded in 96-well plates and randomly divided into 5 groups ( n =6 each):control group (group C),cell injury group (group Ⅰ) and preconditioning with different concentrations of ALC groups (groups A1-3 ).In group C,the cells were incubated with DMEM liquid culture medium containing glucose 0.5 g/L for 3 h.In groups Ⅰ and A1-3 the cells were incubated with DMEM liquid culture medium containing sodium hydrosulfite (Na2S2O4) 3 mmol/L and glucose 0.5 g/L for 3 h,and in addition the cells were pre-incubated with ALC 0.2,0.4 and 0.6 mmol/L for 24 h in groups A1-3 respectively.Cell viability was evaluated by MTF assay,while the apoptosis in cells was detected using TUNEL.The activities of ATPase and SOD and MDA content were also detected.Results Oxygen-glucose deprivation significantly increased the number of apoptotic cells and the content of MDA,and decreased the cell viability and activities of SOD and ATPase in group Ⅰ compared with group C ( P ＜ 0.05).Preconditioning with ALC significantly increased the cell viability and the activities of SOD and ATPaes,and decreased the number of apoptotic cells and the content of MDA in groups A1-3 compared with group Ⅰ ( P ＜ 0.05).Conclusion ALC preconditioning can attenuate PC12 cell injury induced by oxygen-glucose deprivation through inhibition of apoptosis in cells.