Combination Therapy With Fingolimod and Neural Stem Cells Promotes Functional Myelination

Myelination, which occurs predominantly postnatally and continues throughout life, is important for proper neurologic function of the mammalian central nervous system (CNS). We have previously demonstrated that the combination therapy of fingolimod (FTY720) and transplanted neural stem cells (NSCs) had a significantly enhanced therapeutic effect on the chronic stage of experimental autoimmune encephalomyelitis, an animal model of CNS autoimmunity, compared to using either one of them alone. However, reduced disease severity may be secondary to the immunomodulatory effects of FTY720 and NSCs, while whether this therapy directly affects myelinogenesis remains unknown. To investigate this important question, we used three myelination models under minimal or non-inflammatory microenvironments. Our results showed that FTY720 drives NSCs to differentiate into oligodendrocytes and promotes myelination in an ex vivo brain slice culture model, and in the developing CNS of healthy postnatal mice in vivo. Elevated levels of neurotrophic factors, e.g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, were observed in the CNS of the treated infant mice. Further, FTY720 and NSCs efficiently prolonged the survival and improved sensorimotor function of shiverer mice. Together, these data demonstrate a direct effect of FTY720, beyond its known immunomodulatory capacity, in NSC differentiation and myelin development as a novel mechanism underlying its therapeutic effect in demyelinating diseases

Influence of acupuncture on cognitive function and markers of oxidative DNA damage in patients with vascular dementia

AbstractObjectiveTo test the influence of acupuncture on cognitive function and a marker of oxidative DNA damage in patients with vascular dementia (VD).MethodsSixteen VD patients were evaluated before and after acupuncture, using the Folstein Mini-Mental State Examination-Revised (MMSE-R) to assess cognitive function, and the ADL-R scale to assess independence in activities of daily living (ADL). Life quality was evaluated using the DEMQOL (Dementia quality of life questionnaire) questionnaire, and syndromes and expression of vascular dementia were evaluated with the Scale for the Differentiation of Syndromes of Vascular Dementia (SDSVD). In addition, the urine concentration of 8-hydroxy-2′-deoxyguanosine (8-OHdG) —a marker of oxidative damage—was quantified with enzyme-linked immunosorbent assay.ResultsThe MMSE-R and DEMQOL scores were higher after acupuncture than before (P<0.05), while there were no obvious differences in the ADL-R or SDSVD scores (P>0.05). The 8-OHdG content in urine significantly decreased after acupuncture (P<0.05).ConclusionAcupuncture reduces the levels of 8-OHdG and improves cognitive function and quality of life in VD patients, suggesting that acupuncture is beneficial at least in part by preventing oxidative damage

FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms.

FSD-C10, a Fasudil derivative, was shown to reduce severity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through the modulation of the immune response and induction of neuroprotective molecules in the central nervous system (CNS). However, whether FSD-C10 can promote neuroregeneration remains unknown. In this study, we further analyzed the effect of FSD-C10 on neuroprotection and remyelination. FSD-C10-treated mice showed a longer, thicker and more intense MAP2 and synaptophysin positive signal in the CNS, with significantly fewer CD4(+) T cells, macrophages and microglia. Importantly, the CNS of FSD-C10-treated mice showed a shift of activated macrophages/microglia from the type 1 to type 2 status, elevated numbers of oligodendrocyte precursor cells (OPCs) and oligodendrocytes, and increased levels of neurotrophic factors NT-3, GDNF and BDNF. FSD-C10-treated microglia significantly inhibited Th1/Th17 cell differentiation and increased the number of IL-10(+) CD4(+) T cells, and the conditioned medium from FSD-C10-treated microglia promoted OPC survival and oligodendrocyte maturation. Addition of FSD-C10 directly promoted remyelination in a chemical-induced demyelination model on organotypic slice culture, in a BDNF-dependent manner. Together, these findings demonstrate that FSD-C10 promotes neural repair through mechanisms that involved both immunomodulation and induction of neurotrophic factors

Ripple: A Distributed Medium Access Protocol for Multi-hop Wireless Mesh Networks

Abstract-Wireless mesh network, a new wireless broadband access technology, is currently attracting significant attention. This work proposes a distributed medium access protocol, named Ripple, for wireless mesh networks (WMNs) under tree topology. In contrast to existing random-access approaches, Ripple uses a controlled-access approach to protect nodes from unintentional packet collisions and maximize the spatial reuse. The performance of Ripple under an error-free channel was investigated and the accuracy of the analysis was verified by simulation. Simulation results also indicated that Ripple achieved throughput, stability, and QoS enhancement than that of 802.11 DCF under a highly loaded situation in both chain and tree topologies

Fasudil in Combination With Bone Marrow Stromal Cells (BMSCs) Attenuates Alzheimer\u27s Disease-Related Changes Through the Regulation of the Peripheral Immune System.

Alzheimer\u27s disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 1