Institute of Cerebral Vascular Disease of Fujian Province

Fuzhou, China

Institute of Cerebral Vascular Disease of Fujian Province

Fuzhou, China
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Liu N.,Fujian Medical University | Liu N.,Institute of Cerebral Vascular Disease of Fujian Province | Huang H.,Fujian Medical University | Huang H.,Institute of Cerebral Vascular Disease of Fujian Province | And 10 more authors.
Neuroscience | Year: 2011

Recent evidence suggests that exercise improves functional outcome in animal models of cerebral ischemia. Since netrin-1 and its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5B (Unc5B), act as important regulators in neural and vascular activities, we sought to determine whether netrin-1 and DCC and Unc5B are involved in the neuroprotective effects of exercise on rats with induced cerebral ischemia. A total of 108 rats were randomly distributed into three groups: sham-operated group (. n=12), middle cerebral artery occlusion (MCAO) group (. n=48), MCAO+treadmill exercise group (. n=48). Behavioral testing indicated that treadmill exercise could significantly improve neurologic deficits of rats with cerebral ischemia at day 14 and 28 after MCAO (. n=12, P<0.05 and P<0.01), but there was no significant difference at day 4 and 7. Quantitative reverse transcription polymerase chain reaction (qPCR) and Western blot analysis revealed that treadmill exercise enhanced netrin-1 and DCC expression, while it suppressed Unc5B expression in rat peri-ischemic brain area, especially at day 14 and 28 after MCAO (. n=4, P<0.05 or P<0.01). Immunofluorescence analysis showed that in the peri-ischemic area, netrin-1 was expressed in neuronal perikarya, DCC, however, was expressed in neural processes and peri-vascular astrocytes, while Unc5B was expressed mostly in neuronal perikarya and some processes. These results suggest that netrin-1 and its receptors DCC and Unc5B may engage in exercise-induced neural circuit remodeling in the peri-ischemic area, and exercise may promote survival of neurons in this area by regulating netrin-1-Unc5B signaling. Additionally, netrin-1 may also play a role in brain-blood barrier via DCC-immunoreactive peri-vascular astrocytes. In conclusion, we demonstrate that treadmill exercise has beneficial effects that may be attributed, at least in part, to the involvement of netrin-1 and its receptors DCC and Unc5B in the neuronal and vascular activities in brain-ischemic rats. © 2011 IBRO.


Lin L.,Fujian Medical University | Lin L.,Institute of Cerebral Vascular Disease of Fujian Province | Chen H.,Fujian Medical University | Chen H.,Institute of Cerebral Vascular Disease of Fujian Province | And 19 more authors.
PLoS ONE | Year: 2015

IL-10, as a cytokine, has an anti-inflammatory cascade following various injuries, but it remains blurred whether IL-10 protects neurites of cortical neurons after oxygen-glucose deprivation injury. Here, we reported that IL-10, in a concentration-dependent manner, reduced neuronal apoptosis and increased neuronal survival in oxygen-glucose-deprived primary cortical neurons, producing an optimal protective effect at 20ng/ml. After staining NF-H and GAP-43, we found that IL-10 significantly protected neurites in terms of axon length and dendrite number by confocal microscopy. Furthermore, it induced the phosphorylation of AKT, suppressed the activation of caspase-3, and up-regulated the protein expression of GAP-43. In contrast, LY294002, a specific inhibitor of PI3K/AKT, reduced the level of AKT phosphorylation and GAP-43 expression, increased active caspase-3 expression and thus significantly weakened IL-10-mediated protective effect in the OGD-induced injury model. IL-10NA, the IL-10 neutralizing antibody, reduced the level of p-PI3K phosphorylation and increased the expression of active caspase-3. These findings suggest that IL-10 provides neuroprotective effects by protecting neurites through PI3K/AKT signaling pathway in oxygen-glucose-deprived primary cortical neurons. Copyright: © 2015 Lin et al.


Liu Y.,Fujian Medical University | Liu Y.,Institute of Cerebral Vascular Disease of Fujian Province | Zhang Y.,Institute of Cerebral Vascular Disease of Fujian Province | Zhang Y.,Fujian Medical University | And 14 more authors.
PLoS ONE | Year: 2013

Background: Transplantation with bone marrow-derived mesenchymal stem cells (BMSCs) improves the survival of neurons and axonal outgrowth after stroke remains undetermined. Here, we investigated whether PI3K/AKT signaling pathway is involved in these therapeutic effects of BMSCs. Methodology/Principal Findings: (1) BMSCs and cortical neurons were derived fr (OGD), and then were respectively co-cultured for 48 hours with BMSCs at different densities (5×103, 5×105/ml) in transwell co-culture system. The average length of axon and expression of GAP-43 were examined to assess the effect of BMSCs on axonal outgrowth after the damage of neurons induced by OGD. (2) The injured neurons were cultured with a conditioned medium (CM) of BMSCs cultured for 24 hours in neurobasal medium. During the process, we further identified whether PI3K/AKT signaling pathway is involved through the adjunction of LY294002 (a specific phosphatidylinositide-3-kinase (PI3K) inhibitor). Two hours later, the expression of pAKT (phosphorylated AKT) and AKT were analyzed by Western blotting. The length of axons, the expression of GAP-43 and the survival of neurons were measured at 48 hours. Results: Both BMSCs and CM from BMSCs inreased the axonal length and GAP-43 expression in OGD-injured cortical neurons. There was no difference between the effects of BMSCs of 5×105/ml and of 5×103/ml on axonal outgrowth. Expression of pAKT enhanced significantly at 2 hours and the neuron survival increased at 48 hours after the injured neurons cultured with the CM, respectively. These effects of CM were prevented by inhibitor LY294002. Conclusions/Significance: BMSCs promote axonal outgrowth and the survival of neurons against the damage from OGD in vitro by the paracrine effects through PI3K/AKT signaling pathway. © 2013 Liu et al.

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