Fibroblast growth factor-2 counteracts the effect of ciliary neurotrophic factor on spontaneous differentiation in adult hippocampal progenitor cells / 华中科技大学学报（医学）（英德文版）

Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neurotrophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1-100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.

Mechanisms of MPP⁺-induced PC12 cell apoptosis via reactive oxygen species / 华中科技大学学报（医学）（英德文版）

Apoptosis of dopaminergic neurons in the nigrostriatal projection plays a crucial role in the pathogenesis of Parkinson's disease (PD). Although the detailed mechanisms responsible for dopaminergic neuron loss are still under investigation, oxidative stress is identified as a major contributor for neuronal apoptosis. In the current study, we studied the effects of MPP(+), a substrate that mimics oxidative stress, on neuron-like PC12 cells and the underlying mechanisms. PC12 cells were cultured and treated by 100 μmol/L MPP(+) for 4, 8, 16, 24 and 48 h, respectively. For drug pretreatment, the PC12 cells were incubated with N-acetyl-l-cysteine (NAC, 5 mmol/L), an antioxidant, SP600125 (20 μmol/L) or PD98059 (100 μmol/L), two pharmacological inhibitors of JNK and ERK1/2, for 1 h before addition of MPP(+). Cell apoptosis was measured by flow cytometry. The mRNA expression of Cu(2+)/Zn(2+)-SOD, GSH-Px, Bcl-2 and Bax was detected by RT-PCR. The protein expression of p-ERK1/2 and p-JNK was determined by Western blotting. Our results showed that MPP(+) exposure could induce substantial PC12 cell apoptosis. The pretreatment of SP600125 or PD98059 could effectively reduce the apoptosis rate by reducing the ratio of Bax/Bcl-2 mRNA levels. MPP(+) exposure also induced high level of reactive oxygen species (ROS), marked by dramatic increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNA levels. The elevated ROS was strongly associated with the activation of JNK and ERK1/2 signal pathways after MPP(+) exposure, since the pretreatment of NAC significantly reduced the upregulation of p-JNK and p-ERK1/2. Finally, the pretreatment of SP600125, but not PD98059, alleviated the increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNAs induced by MPP(+), suggesting that the activation of the JNK signal pathway, but not the ERK1/2 signal pathway, could, in some degree, antagonize the generation of ROS induced by oxidative stress. In conclusion, our results suggest that JNK and ERK1/2 signal pathways, which are activated via ROS, play a crucial role in neuronal apoptosis induced by oxidative stress.

Mechanisms of MPP⁺-induced PC12 cell apoptosis via reactive oxygen species / 华中科技大学学报（医学）（英德文版）

Apoptosis of dopaminergic neurons in the nigrostriatal projection plays a crucial role in the pathogenesis of Parkinson's disease (PD). Although the detailed mechanisms responsible for dopaminergic neuron loss are still under investigation, oxidative stress is identified as a major contributor for neuronal apoptosis. In the current study, we studied the effects of MPP(+), a substrate that mimics oxidative stress, on neuron-like PC12 cells and the underlying mechanisms. PC12 cells were cultured and treated by 100 μmol/L MPP(+) for 4, 8, 16, 24 and 48 h, respectively. For drug pretreatment, the PC12 cells were incubated with N-acetyl-l-cysteine (NAC, 5 mmol/L), an antioxidant, SP600125 (20 μmol/L) or PD98059 (100 μmol/L), two pharmacological inhibitors of JNK and ERK1/2, for 1 h before addition of MPP(+). Cell apoptosis was measured by flow cytometry. The mRNA expression of Cu(2+)/Zn(2+)-SOD, GSH-Px, Bcl-2 and Bax was detected by RT-PCR. The protein expression of p-ERK1/2 and p-JNK was determined by Western blotting. Our results showed that MPP(+) exposure could induce substantial PC12 cell apoptosis. The pretreatment of SP600125 or PD98059 could effectively reduce the apoptosis rate by reducing the ratio of Bax/Bcl-2 mRNA levels. MPP(+) exposure also induced high level of reactive oxygen species (ROS), marked by dramatic increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNA levels. The elevated ROS was strongly associated with the activation of JNK and ERK1/2 signal pathways after MPP(+) exposure, since the pretreatment of NAC significantly reduced the upregulation of p-JNK and p-ERK1/2. Finally, the pretreatment of SP600125, but not PD98059, alleviated the increase of Cu(2+)/Zn(2+)-SOD and GSH-Px mRNAs induced by MPP(+), suggesting that the activation of the JNK signal pathway, but not the ERK1/2 signal pathway, could, in some degree, antagonize the generation of ROS induced by oxidative stress. In conclusion, our results suggest that JNK and ERK1/2 signal pathways, which are activated via ROS, play a crucial role in neuronal apoptosis induced by oxidative stress.

Fibroblast growth factor-2 counteracts the effect of ciliary neurotrophic factor on spontaneous differentiation in adult hippocampal progenitor cells / 华中科技大学学报（医学）（英德文版）

Neural stem/progenitor cells (NSCs) can spontaneously differentiate into neurons and glial cells in the absence of mitogen fibroblast growth factor-2 (FGF-2) or epidermal growth factor (EGF) in medium and the spontaneous differentiation of NSCs is mediated partially by endogenous ciliary neurotrophic factor (CNTF). This study examined the relationship of FGF-2 and CNTF in the spontaneous differentiation of adult hippocampal progenitor cells (AHPs). AHPs were cultured in the medium containing different concentration of FGF-2 (1-100 ng/mL). Western blotting and immunofluorescence staining were applied to detect the expression of the astrocytic marker GFAP, the neuronal marker Tuj1, the oligodendrocytic marker CNPase and, Nestin, the marker of AHPs. The expression of endogenous CNTF in AHPs at early (passage 4) and late stage (passage 22) was also measured by Western blotting. The results showed that FGF-2 increased the expression of Nestin, dramatically inhibited the expression of GFAP and Tuj1 and slightly suppressed the expression of CNPase. FGF-2 down-regulated the expression of endogenous CNTF in AHPs at both early (passage 4) and late stage (passage 22). These results suggested that FGF-2 could inhibit the spontaneous differentiation of cultured AHPs by negatively regulating the expression of endogenous CNTF in AHPs.

Meta-analysis of pramipexole in treatment of restless legs syndrome / 中华神经科杂志

Objective To evaluate the efficacy and safety of pramipexole in treating restless legs syndrome (RLS).Methods A search for randomized,double-blind,and placebo-controlled clinical trials of pramipexole in treating moderate to severe RLS using CNKI,PubMed,Embase and Cochrane Library database was carried out. A meta-analysis of included clinical trials was performed with RevMan 5.0 software.The 2 outcomes that the weighted mean difference(WMD) of change from baseline in International RLS Study Group rating scale(IRLS) score and the relative risk (RR) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score were calculated for efficacy.Safety was assessed with RR of the adverse event (AE).Results A total of 5 clinical trials were included in this meta-analysis,of which 1776 patients were randomly assigned (945 on pramipexole,831 on placebo).The records of patients were pooled.Overall WMD were - 6.34 ( Z =12.76,P ＜ 0.01 ) for the change from baseline in IRLS score,and RR of response based on CGI-I were 1.65 (Z =10.39,P ＜0.01).The overall RR of pramipexole versus placebo were 1.14 ( Z =1.87,P =0.06 ) for AE.Conclusion To treat RLS,pramipexole is an effective and safe drug.

Human 14-3-3γ gene transfer may protect dopaminergic neurons in rat of Parkinson's disease / 中华老年医学杂志

Objective To explore the effects of 14-3-3 γ gene on dopaminergic neurons of PD rat model.Methods 6 hydroxydopamine (6-OHDA) was injected into the corpus striatum of 60 SD rats to establish PD model.A week later,Ad/14-3-3 γ was injected into the corpus striatum of 16 rats,while PBS and Ad-LacZ were injected into the corpus striatum of 16 and 28 rats,respectively,as control.X-gal dyeing was utilized to examine the LacZ reporter gene expression in the corpus striatum at 3 day,2 week and 6 week.Real-time PCR was utilized to test the expression level of 14-3-3 γmRNA at 2 weeks after Ad/14-3-3 γ injection.Immunohistochemistry technique was used to detect TH positive neurons and fibers in the corpus striatum and substantial nigra.Western blotting was performed to check the expression of 14-3-3 γ in the corpus striatum at 2 weeks and caspase-3 at 6 veeks after Ad/14-3-3 γ injection.High performance liquid chromatography (HPLC) method was used to examine the contents of DA and DOPAC in the corpus striatum.The rats underwent rotational ethological examination at 1,2 and 6 weeks after the second injection.Results The expression of β-gal,which showed the successful LacZ gene transfection,was found in the corpus striatum of LacZ groups.The 14-3-3 γ mRNA and protein expression in the corpus striatum were significantly higher in the Ad/14-3-3 γ group than in the other two groups.The TH-positive cell ratio of substania nigra to contralateral area in the lesion side was 0.44±0.17 and the optical density (OD) of TH-positive fibers was 0.62±0.14 in the Ad/14-3-3 γ group,both higher than those in PBS group (0.16±0.13 and 0.36±0.15) and LacZ group (0.15±0.09 and 0.30±0.11) (all P＜0.01).The contents of DA and DOPAC in the lesion sides of corpus striatum were increased in the Ad/14-3-3 γ group [(248± 116)ng/g and (752±177) ng/g] than in PBS group [(106±35) ng/g and (724±159) ng/g] and LacZ group [(136±49) ng/g and (765±163) ng/g] (P＜0.01).The DA and DOPAC ratios of the lesion side of corpus striatum to the contralateral side were 0.37±0.14 and 0.38±0.17 in the Ad/14-3-3 γgroup,higher than those in PBS group (0.15±0.08 and 0.13±0.10,respectively) and LacZ group (0.19±0.11 and 0.16±0.09 (all P＜0.01).The expression level of caspase-3 was decreased in Ad/14-3-3 γ group than in PBS and LacZ groups at 6 weeks after the second injection.The turns/min induced by apomorphine in Ad/14-3-3 γ group were 9.4 ± 2.5 at 1 week after the Ad/14-3-3 γinjection,and reduced to 4.6±2.2 at 6 weeks later.While in PBS and LacZ group,the turns were 14.5±4.9 and 13.8±3.5 at 1 week after the second injection,6 weeks later rised to 18.7±5.2 and 20.6± 6.7 respectively,significantly higher than those in Ad/14-3-3 γ group (all P＜0.01).Conclusions 14-3-3γ gene transfer has a protective effect on the dopaminergic neurons and it may be a promising candidate gene for curing PD.

Correlation study on expression of GST-π protein in brain tissue and peripheral blood of epilepsy rats induced by pilocarpine / 华中科技大学学报（医学）（英德文版）

Previous studies have suggested that glutathione-S-transferase π (GST-π) over-expression in the brain tissue is associated with refractory epilepsy. However, whether the change in GST-π level in the peripheral blood is in line with that in brain tissue remains unknown. This study examined the correlation between GST-π in brain tissue and that in peripheral blood in rat models of pilocarpine-induced refractory epilepsy. The animals were divided into drug-resistant group and drug-responsive group according to the response to anti-epileptic drugs. GST-π expression in brain tissue was immunohistochemically determined, while the expression of GST-π in peripheral blood was analyzed by Western blotting. In the hippocampus and cortex, GST-π was mainly found in the cytoplasm and membrane of neurons, and the GST-π expression level was higher in drug-resistant group than in the drug-responsive group and saline control group (P0.05). The change in expression of GST-π in peripheral blood showed the same pattern as that in brain tissues, suggesting GST-π might contribute to drug resistance in epilepsy. Importantly, the GST-π over-expression in peripheral blood could be used as a marker for resistance to anti-epileptic agents.

Curcumin Antagonizes Rotenone-induced Injury of PC12 Cells by Antioxidant Activity / 华中科技大学学报(医学版)

Objective To investigate the cytoprotection of curcumin against rotenone(Ro)-induced injury and the molecular mechanisms underlying in PC12 cells.Methods The insulted model of PC12 cells was established with Ro.Cell viability was determined using MTT reduction assay.The content of reactive oxygen species(ROS)was determined by the method of DCFH-DA staining.Chromatometry was used to measure the total activity of SOD,DCFH-DA staining to measure the level of intracellular ROS,and flow cytometry to assay the apoptosis rate.Results 0.5 and 1.0 μmol/L curcumin significantly decreased the inhibitory rate of Ro on the growth of PC12 cells for 24 h as compared with the Ro group(P＜0.01).0.5 and 1.0 μmol/L curcumin significantly ameliorated the changes in morphology of PC12 cells,increased the activities of intracellular SOD as compared with the Ro group(P＜0.05),decreased the production of intracellular ROS and inhibited the apoptosis of PC12 cells induced by Ro for 24 h as compared with Ro group(P＜0.01).Conclusion Curcumin can resist Ro-induced cytotoxicity probably by the mechanism of scavenging intracellular ROS and increasing the activity of antioxidase.

Changes in synaptophysin and growth associated protein-43 mRNA around a cerebral infarction after mobility training / 中华物理医学与康复杂志

Objective To investigate the effects of mobility training on mobility and the mRNA levels of both synaptophysin and growth associated protein 43 (GAP-43) in the region around an infarction in rats with acute cerebral infarction. Methods Models of cerebral infarction were created in 100 rats through middle cerebral artery occlusion. They were then randomly divided into training and control groups. The motor skill of the rats was examined using a beam walking test. The mRNA levels of both synaptophysin and GAP-43 in the region around the infarction were observed at the 1st, 3rd, 7th, 14th and 28th days after model-creation using a semi-quantitive reverse transcrip-tion polymerase chain reaction. Results The rats' mobility scores increased with training, and significant differ-ences were observed between the average scores of the two groups at the 3rd, 7th and 14th days. The scores were higher in the training group. The mRNA levels of both synaptophysin and GAP-43 in the region around the infarction increased significantly from the 1st to the 3rd and 7th days. Synaptophysin mRNA levels were significantly higher in the trained group at each time point, but the levels of GAP-43 mRNA were significantly higher in the trained group only on the 3rd and 7th days. Conclusions Motor skill and the mRNA levels of synaptophysin and GAP-43 in the region around an infarction can be increased by motor skill training, at least in rats with model acute cerebral infarc-tion.

A randomized controlled trial of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease / 中华老年医学杂志

Objective To investigate the efficacy and safety of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease ( PD). Methods A randomized, clinical trial of pramipexole versus fluoxetine treatment for 12 weeks in 50 patients suffering from combined PD and depression was accomplished. The efficacy and safety assessments of the treatments were performed at different time points. Results For the intent-to-treat (ITT) population, the Hamilton Depression Rating Scale (HAMD) scores decreased progressively in both the pramipexole and the fluoxetine group, and a between-time statistical analysis was significant for both groups. The efficacy proportion of patients who responded to the treatment, as defined by at least a 50% reduction in HAMD score, was 56. 0% in the pramipexole group versus 48. 0% in the fluoxetine group (χ~2 =0. 321, P>0. 05). Similarly, the proportion of patients who recovered, as defined by a final HAMD score ≤8, was 52. 0% in the pramipexole group versus 32. 0% in the fluoxetine group (χ~2 =2. 053, P>0. 05) , but the difference between the two treatments showed no statistical significance. At the endpoint, both the Unified Parkinson's Disease Rating Scale (UPDRS) part Ⅱ and part Ⅲ subscores improved in the pramipexole group, by a mean of 2. 9±3. 7 (t= 2.366, P<0.05) and7.2±5.1 (t=2.654, P< 0.05), respectively, and the latter was significantly different from the change in this variable of the fluoxetine group (P<0. 05). Spearman analysis showed that no relationship between HAMD score and UPDRS Part II or Part III subscore. The findings for the per-protocol (PP) population were consistent with the above results, except that the proportion of patients who recovered in the pramipexole group was significantly larger than that in the fluoxetine group. The adverse events in both groups were mild dizziness, nausea and anorexia. No significant difference was found in the frequencies of the adverse events between the pramipexole and fluoxetine group. Conclusions Pramipexole is effective and safe in the treatment of Chinese PD patients combined with depression.

The protection of carbamylated erythropoietin on focal ischemic brain injury / 中华神经科杂志

Objective To study the protection and its mechanism of carbamylated erythropoietin (CEPO) on ischemic brain injury and to compare its function with erythropoietin (EPO).Methods Focal cerebral ischemia/reperfusion was induced by occlusion of the middle cerebral artery (MCAO) using the intraluminal filament technique.The expression of endothelial NO synthase (eNOS) and activated caspase-3 were detected with Western blot.The inducible NO synthase (iNOS) positive cells were detected by immunohistochemistry staining.The apoptotic cell was detected by TUNEL staining.Results The expression of eNOS, iNOS and activated caspase-3 in cerebral cortex significantly increased after MCAO.The influence of CEPO and EPO on eNOS in ischemic cortex were not significantly different.However, the expression of activated caspase-3 markedly dropped from 95.4%±16.7% in group NS to 43.5%±13.1% in group CEPO and 45.1%±11.2% in group EPO (t=5.99 and 6.13,P<0.01).Immunohistochemistry staining revealed iNOS positive cells in ischemic cortex was (3.1±1.9) cells/square, CEPO and EPO remarkably reduced them to (0.7±0.2) cells/square and (0.8±0.2) cells/square, respectively (t=3.08 and 2.95, P < 0.05).The apoptotic cells in ischemic cortex fell from (94.2±15.2) cells/square in group NS to (40.5±9.8) cells/square in group CEPO (t=7.27, P < 0.01), the anti-apoptosis by EPO was similar to CEPO.Conclusion CEPO and EPO have the similar function of anti-apoptosis by inhibiting expression of activated caspase-3 and iNOS.

The neuroprotection of edaravone and GM1 on the rat model of parkinson disease / 中华行为医学与脑科学杂志

Objective To investigate the protect effects of Edaravone(Ed)and GM1 on the rat model of parkinson disease(PD).Methods To establish the unilateral PD rat model,6-OHDA was injected at two points of right substantial nigra pars compacta(SNC),ventral tegmental area(VTA),then the old rats were randomly divided into normal,NS,PD,PD + GMI,PD + Ed,FD + GM1 + Ed six groups.14d later,a rotational test induced by apomorphine was performed to determine the successful ratio.Cell apoptosis in SNC of rats were examined by TUNEL methods.Results Normal and NS groups unappeared rotate action by APO,and have no cell apoptosis in SNC.The other groups all appear rotate action(＞7 r/min)by APO,rotate action were in following gradation:PD +GM1 + Ed group(8.0±0.3)＜PD + Ed group(12.0±0.6)＜PD + GM1 group(17.0±1.0)＜PD group(23.0±1.3)(P＜0.01);and cell apoptosis in SNC were in following gradation:PD + GM1 + Ed group(27.63±2.38)＜PD + Ed group(38.42±3.54)＜PD + GM1 group(49.36±3.12)＜PD group(62.61±4.03)(P＜0.01).Conclusion 6-OHDA could induce change of action of rat and cell apoptosis in SNC.GM1,Ed reduce significantly the effect induced by 6-OHDA.GM1 combining with Ed have the best effects.

Prevalence and its impacting factors of non-motor symptoms in Parkinson's disease / 中华老年医学杂志

Objective To explore the incidence rate, total incidence numbers and possible impacting factors of non-motor symptoms (NMSs) in Parkinson's disease (PD). Methods The NMS questionnaire (NMS Quest) was used to investigate 131 out-patients diagnosed with PD, and the prevalence of each item, the total NMS numbers and their relationships with clinical features were assessed. Results All of the patients, who were distributed in every stage of PD, had NMSs and each case with 11 items on average. Autonomic symptoms such as nocturia and constipation were the most frequent ones. The patients over 65 versus less than 65 years old had a higher prevalence in a number of items such as olfactory disturbance, dysphagia and constipation. At the same time, the rigidity subtype patients had a higher prevalence in depression items than the tremor subtype ones.The total number of NMS was positively correlated with course of disease, age, UPDRS score and Hoehn & Yahr (H&Y) stage. Conclusions NMSs are common among PD patients. While the prevalence of each item may vary with different clinical features, the total number of NMS is increased with the severity of PD. More attention should be paid to the diagnosis and rational treatment of the NMSs.

A meta-analysis of mood stabilizers for Alzheimer's disease / 华中科技大学学报（医学）（英德文版）

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer's disease (AD). We searched 5 databases from their inception to January 2010. Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included. These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation. Methodological quality was assessed using the Jadad score. The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04). There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo. Only one of these studies was free of methodological limitations (Jadad score=5). In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Neuroprotection of mild brain hypothermia against cerebral ischemic injury / 中华物理医学与康复杂志

Objective To study the effect of mild brain hyothermia on cerebral ischemic injury. Methods Global cerebral ischemia was established by modified Pulsinelli 4-vessel occlusion model. Forty-eight Sprague-Dawley rats were divided into 4 group: a sham-operated group, a normothermia (37～38℃) ischemic group and a mild is-chemic hypothermia (31～32℃) group; the mild ischemic hypothermia was subdivided into 4 groups with the hypo-thermia lasting for 30 min, 60 min, 120 min and 240 min, respectively. After 240 rain of reperfusion following 20 min cerebral ischemia, the levels of nitric oxide products nitrite (NO2) ,endothelin-1 (ET1) , tumor necrosis fac-tor alpha (TNFα) and interleukin-1 beta (IL-1β) in brain tissue and the lactate dehydrogenase (LDH), aspartate aminotransferase(AST) , creatine kinase(CK) and its brain band isoenzyme (CK-BB) in plasma were measured. Results The levels of IL-1β,TNFα, ET1 and NO2. in brain tissue, and the amounts of LDH, AST, CK and CK-BB in serum were higher in normothermia ischemic group than those in sham-operated group (P <0.05). Mild hypother-mia lasting for 60 min to 240 min markedly decreased the levels of IL-1β, TNF-α, ET1 and NO2 in brain tissue, and the amounts of LDH, AST, CK and CK-BB in serum in normothermia ischemic group, when compared with normo-thermia ischemic group (P < 0.05 or P < 0.01). Mild hypothermia lasting for 30 min did not influence the content of IL-1β, TNF-α, ET1 and NO2 in brain tissue when compared with normothermia isehemia group (P > 0.05). Con-clusion Mild brain hypothermia post-ischemia can significantly suppress the inflammation response in ischemic brain tissue and stabilize the function of cell membrane. The best neuroprotection of mild brain hypothermia must be carried out immediately and last for more than 60 minutes.

Progress in stem cell therapy for Alzheimer's disease / 国际生物医学工程杂志

Stem ceils transplantation is one of the potential therapeutic strategies for Alzheimer's disease (AD). Many animal models following stem cell transplantation showed improvement in memory and cognitive function. However, the pathological changes in AD, such as arnyloid beta deposits, negatively affect the survival and differentiaition of stem cells. Stem cells transfectcd with neprilysin or administration of phenserine could at-tenuate these adverse effects. Genetic modification of stem cell by over expression of neurotrophic factors could attenuate the adverse effects not only on stem cells but also on degenerative neurons. Further investigation on how to overcome the adverse effects of phathological factors in AD on stem cells and maximize the therapeutic effects of stem cells would support the hope for introduction of stem cells transplation into clinical application.

Extracellular signal-regulated kinases 1 and 2 regulating rotenone-induced injury in pheochromocytoma cells / 中华神经科杂志

Objective To investigate the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rotenone-mediated dopaminergic cell damage. Methods Neuronal rat adrenal pheochromecytoma(PC12) cells treated with rotenone were used as the cell model of Parkinson' s disease (PD). Cell viability of PC12 cells after exposure to rotenone was detected by MTT (methyl thiazolyl tetrazolium) method. Immanohistechemistry was used to detect the phosphorylation of ERK1/2 in cells exposed to rotenone. Western blotting was used to verify the phosphorylation of ERK1/2 and to observe the effect of PD98059, an inhibitor of the upstream mitogen activated protein kinase kinase (MEK) that phosphorylates and activates ERK1/2, on rotenone-induced ERK1/2 phosphorylation and cell viability.Results The viability (represented by A570 of PC12 cells exposed to 5 μmoL/L rotenone) declined with the increase of exposure time from 1 h to 24 h (%, 1 h :75.46±5.47, 2 h : 70.42±1.94, 4 h : 65.23± 0.96, 8 h : 59.04 ± 2.85, 24 h :29.64 ± 1.63, comparison between different time points(F=143.014, P=0.000) ; compared with control groups(100.00±2.89), q value: 17.07, 20.58, 24. 19, 28.50, 48.95 respectively, all P <0.01). After exposure to rotenone, phosphorylated ERK1/2 aggregated in the PC12 cells. Western blotting indicated that rotenone induced a biphasic phosphorylation of ERK1/2, which increased from 30 min after rotenone treatment, reached the peak at 1-2 h, decreased at 4 h, and increased again at 8 h, and disappeared after 16 h; PD98059 significantly inhibited ERK1/2 phosphorylation induced by rotenone, and attenuated cell injury examined at 1, 2 and 8 h. Conclusions Our study suggested that ERK1/2 activation plays a detrimental role in rotenone toxicity, and raised the possibility that abnormal patterns of ERK1/2 activation may contribute to dopaminergic neuronal cell death in PD.

Depression in patients with Parkinson's disease and the associated features / 华中科技大学学报（医学）（英德文版）

The study was aimed to examine the prevalence of depression in patients with Parkinson's disease (PD) and identify its features. A total of 131 out-patients, diagnosed as having idiopathic PD in accordance with the United Kingdom Parkinson's Disease Society Brain Bank criteria, were interviewed with questionnaire and evaluated by Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale (UPDRS), Hohen &Yahr staging (H&Y staging) and Hamilton Rating Scale for Depression (HRSD). Patients were divided into three groups in terms of HRSD score: depression group, sub-threshold depression group and non-depression group. The clinical variables and symptom profiles were obtained and compared among the three groups. The results showed that 27 patients (20.6%) fell into the depression group, 71 (54.2%) into the sub-threshold depression group, and 33 (25.2%) into the non-depression group. There were no differences in age, gender or tremor score among the groups (P>0.05). Significant differences were found in duration of PD, UPDRS score, rigidity score and H&Y stage between the sub-threshold depression group (or the depression group) and the non-depression group (P<0.05). Moreover, the clinical variables in the subthreshold depression group had the trend of increasing with the severity of PD and their values were similar to those in the depression group. Anhedonia, feeling of incapability, sleep disturbance, gastrointestinal symptoms and depressive moods were most common in the depression group. And these symptoms also were more common in the other two groups. It is concluded that depression and sub-threshold depression are common in PD and share similar clinical features. Furthermore, subthreshold depression might be the prodrome of depression and may develop into depression as the condition progresses.

Clinical investigation of mild cognitive impairment in patients with Parkinson's disease / 中华神经科杂志

Objective To describe the prevalence and neuropsychological character of mild cognitive impairment (MCI) associated with Parkinson' s disease(PD-MCI). Methods One hundred and three PD patients and a control group of 32 healthy old subjects were chosen. Psychometric assessment included the Mini Mental State Examination, the Dementia Rating Scale and a series of neuropsychol ogicaltests. The Hamilton Rating Scale of Depression was used to assess depression in PD patients. Results (1)Twenty-one (20.4%) PD patients was diagnosed with dementia, 45 (43.7%) had a MCI and only 37(35.9%) had no cognitive impairment; (2) Subjects with PD-MCI were older, had a later onset of the PD,and displayed more severe motor symptoms compared with those without cognitive impairment; (3) The prevalence and neuropsychological profile of PD-MCI were thought to correlate with the dominating side and subtype of Parkinsonian symptoms, for patients with left-sided dominant symptoms had a significantly higher chance of suffering MCI than those with right-sided dominant symptoms, the ratio being 74.2% vs 42.2%,χ<'2 =7. 589,P <0.05; The tremor-dominant group took less time than the mixed group for Stroop word test measurement ((80.8±39.9) s vs (94.4±30.0) s,t=3.332,P<0.01). Conclusion Identification of MCI is of important clinical significance, which helps to treat patients differently and thus predict the prognosis.

Transplantation of bone marrow multipotent adult progenitor cells for treating Parkinson disease in rats / 中国组织工程研究

BACKGROUND: Parkinson disease is a common degenerative disorder of nervous system. Transplantation of embryonic stem cell can alleviate the symptoms of Parkinson disease, but restricted technically and ethically. Compared with embryonic stem cell, the various characteristics of bone marrow derived-multipotent adult progenitor cells (MAPCs) enable them to become one the ideal sources of cells for cell transplantation.OBJECTIVE: To explore the hypothesis that MAPCs were able to enter the brain and reduce the neurological functional deficits in rats by injecting intravenously.DESTGN: A randomized controlled experiment.ETTING: Department of Neurology, Wuhan First Hospital.MATERIALS: The experiments were performed in the laboratory of Department of Neurology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from October 2003 to March 2005. Eighty healthy Sprague-Dawley (SD) rats of 180-200 g were provided by the experimental animal center of Tongji Medical College,Huazhong University of Science and Technology.METHODS: The rats were made into models of Parkinson disease, the bone marrow-derived MAPCs, which were in vitro purified, proliferated and treated with 5-bromo-2-deoxyuridine (BrdU), were injected via caudal vein. After three months,the immunohistochemical technique, reverse transcription-polymerase chain reaction (RT-PCR), electron microscopy and behavioral tests were used to identify the MAPCs or neuron-like cells derived from MAPCs in brain and their functions.MAIN OUTCOME MEASURES: ① Results of behavioral observation; ② Results of immunihistochemical staining.RESULTS: After implantation, MAPCs could survive and differentiate into neuron-like cells in substantia nigra and striatum. MAPCs-derived dopaminergic neurons caused gradual and sustained behavioral restoration of 6-hydroxydopamine (6-OHDA)-mediated motor asymmetry. The levels of dopamine beta-hydroxylase (DBH), nerve growth factor (NGF) or dopamine transporter (DAT) mRNA were up-regulated significantly. It was observed under electron microscope that immature synapse implicated MAPCs- derived neuron should play an important role in the reconstruction of neural circuitry.CONCLUSION: Transplanted bone marrow derived-MAPCs can spontaneously differentiate into dopaminergic neurons,and act the corresponding nerve function.