He W.,Hebei Medical University |
He W.,Hebei Key Laboratory for Neurology |
He W.,Hebei Collaborative Innovation Center for Cardio cerebrovascular Disease |
He W.,Hebei Key Laboratory of Vascular Homeostasis |
And 20 more authors.
Neurochemical Research | Year: 2015
Sonic hedgehog (Shh), a secreted glycoprotein factor, can activate the Shh pathway, which has been implicated in neuronal polarization involving neurite outgrowth. However, little evidence is available about the effect of Shh on neurite outgrowth in primary cortical neurons and its potential mechanism. Here, we revealed that Shh increased neurite outgrowth in primary cortical neurons, while the Shh pathway inhibitor (cyclopamine, CPM) partially suppressed Shh-induced neurite outgrowth. Similar results were found for the expressions of Shh and Patched genes in Shh-induced primary cortical neurons. Moreover, Shh increased the levels of brain-derived neurotrophic factor (BDNF) not only in lysates and in culture medium but also in the longest neurites of primary cortical neurons, which was partially blocked by CPM. In addition, blocking of BDNF action suppressed Shh-mediated neurite elongation in primary cortical neurons. In conclusion, these findings suggest that Shh promotes neurite outgrowth in primary cortical neurons at least partially through modulating BDNF expression. © 2015 Springer Science+Business Media New York
Zhang L.,Hebei Medical University |
Zhang L.,Hebei Collaborative Innovation Center for Cardio cerebrovascular Disease |
Zhang L.,Hebei Key Laboratory of Vascular Homeostasis |
Zhang X.,Hebei Medical University |
And 30 more authors.
Brain Research | Year: 2016
Background Post-ischemic oxidative stress and inflammation play pivotal roles in the pathogenesis of ischemic stroke and may represent therapeutic targets. Nobiletin (NOB) has been reported to elicit a variety of biological effects through its anti-oxidant and anti-inflammatory properties. Our previous study has demonstrated the beneficial effect of NOB in ischemic stroke, but the underlying mechanisms remain poorly defined. We therefore further investigated the role of NOB in cerebral ischemia and its potential mechanisms. Methods Adult male Sprague-Dawley rats were randomly assigned to five groups: Sham (sham-operated+0.05% Tween-80), permanent middle cerebral artery occlusion (pMCAO+0.9% saline), Vehicle (pMCAO+0.05% Tween-80), NOB-L (pMCAO+NOB 10 mg/kg) and NOB-H (pMCAO+NOB 25 mg/kg) groups. Rats were pre-administered intraperitoneally once daily for 3 days prior to ischemia and then received once again immediately after surgery. Neurological deficit, brain edema and infarct volume were evaluated at 24 h after stroke. Immunohistochemistry, western blot and RT-qPCR were used to detect the expression of Nrf2, HO-1, SOD1, NF-κB and MMP-9. SOD1, GSH and MDA were measured by spectrophotometer. Results Compared with Vehicle group, neurological deficits and brain edema were relieved in NOB-H group, infarct volume was lessened in both NOB-L and NOB-H groups (P<0.05). NOB significantly increased the expression of Nrf2, HO-1, SOD1 and GSH, while decreased the levels of NF-κB, MMP-9 and MDA (P<0.05). Conclusion NOB may have a neuroprotective effect on cerebral ischemia, and this protection may be through upregulating Nrf2, HO-1 and downregulating NF-κB expression. © 2016 Elsevier B.V. All rights reserved.