Recombinant Human Ciliary Neurotrophic Factor Protects MCAO/R Rat Brain against Neuronal Degeneration and Apoptosis by Regulating NOS Expression

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To research the effects and mechanisms of recombinant human ciliary neurotrophic factor (rhCNTF) on ischemia/reperfusion in vivo and in vitro, rhCNTF was biosynthesized, and ischemia/reperfusion-like models were used. Protection by rhCNTF was studied at the in vivo level using a model of middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. RhCNTF was administrated just before reperfusion. RhCNTF markedly increased animal viability, decreased infarct volumes and neurological deficit scores. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation/reoxygenation, and treated with rhCNTF prophylactically. Results indicated that neuronal survival rates were increased, LDH release was decreased and lose of neurite length were alleviated in rhCNTF group, and this protection was associated with nerotrophic effect, nitric oxide and neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS). The data suggest that rhCNTF may be a good therapeutic reagent to reduce cerebral ischemia/reperfusion injury, and may act by NOS regulation.

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May 2013

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[1] Watt, J.A., Bone, S., Pressler, M., Cranston, H.J., Paden, C.M., "Ciliary neurotrophic factor is expressed in the magnocellular neurosecretory systemof the rat in vivo: Evidence for injury- and activity-induced upregulation, " Exp. Neurol, vol.197, no.1, Jan 2006,pp.206-214.

DOI: 10.1016/j.expneurol.2005.09.009

Google Scholar

[2] Liu, QS., Wang, QJ., Du, GH., Zhu, SY, Gao M, Zhang L., Zhu, JM., Cao, JF. "Recombinant human ciliary neurotrophic factor reduces weight partly by regulating nuclear respiratory factor 1 and mitochondrial transcription factor A," Eropean Journal of Pharmacology, vol.563, no.1-3 ,Jun, 2007, pp.77-82

DOI: 10.1016/j.ejphar.2007.02.034

Google Scholar

[3] Kelleher, M.O., Myles, L.M., Al-Abri, R.K., Glasby, M.A. "The use of ciliary neurotrophic factor to promote recovery after peripheral nerve injury by delivering it at the site of the cell body," Acta Neurochir. (Wien) , vol 148, no.1, Jan 2006, p.55–61.

DOI: 10.1007/s00701-005-0631-2

Google Scholar

[4] Macrae, I.M. " New models of focal cerebral ischemia. Br," Clin. Pharmacol, vol34, no.4, Oct 1992, p.302–308.

Google Scholar

[5] Zea Longa, E.L., Weinstein, P.R., Carlson, S., Cummins, R. "Reversible middle cerebral artery occlusion without craniectomy in the rats," Stroke, vol20, no.1, Jan 1989,p.84–91

DOI: 10.1161/01.str.20.1.84

Google Scholar

[6] Tu, Y., Kroener, S., Abernathy, K., Lapish, C., Seamans, J., Chandler L.J., Woodward, J.J. "Ethanol inhibits persistent activity in prefrontal cortical neurons.," Neurosci , vol 27, no.17, Apr 2007,p.4765–4775.

DOI: 10.1523/jneurosci.5378-06.2007

Google Scholar

[7] Henne, W.M., Oomman, S., Attridge, J., Finckbone, V., Coates, P., Bliss, R., Strahlendorf, H., Strahlendorf, J. "AMPA-induced excitotoxicity increases nuclear levels of CAD, endonuclease G,and acinus and induces chromatin condensation in rat hippocampal pyramidal neurons," Cell Mol. Neurobiol, vol 26, no.3, May 2006, p.321–339.

DOI: 10.1007/s10571-006-9031-2

Google Scholar

[8] Ban, J.Y., Jeon, S.Y., Nguyen, T.T., Bae, K., Song, K.S., Seong, Y.H.. "Neuroprotective effect of oxyresveratrol from Smilacis chinae rhizome on amyloid Beta protein (25–35)-induced neurotoxicity in cultured rat cortical neurons,"Biol Pharm Bull , vol 29, no.12, Dec 2006,p.2419–2424.

DOI: 10.1248/bpb.29.2419

Google Scholar

[9] Rama Rao, K.V., Panickar, K.S., Jayakumar, A.R. Norenberg, M.D. "Astrocytes protect neurons from Ammonia toxicity," Neurochem. Res , vol 30, no.10, Oct 2005, p.1311–1318.

DOI: 10.1007/s11064-005-8803-2

Google Scholar

[10] Liu, QS., Gao, M, Zhu SY, Li SJ, Zhang L, Wang QJ, Du GH.. "The novel mechanism of recombinant human ciliary neurotrophic factor on the anti-diabetes activity," Basic Clin Pharmacol Toxicol, vol.101, no.2, Aug 2007,pp.78-84.

DOI: 10.1111/j.1742-7843.2007.00092.x

Google Scholar

[11] Jiang, R.G., Eyzaguirre, C.. "Effects of hypoxia and putative transmitters on [Ca2+]i of rat glomus cells," Brain Res, vol.91, no.10, May 2004, p.285–296

DOI: 10.1016/j.brainres.2003.09.075

Google Scholar

[12] Rui Liu, Mei Gao, Zhi-Hong Yang, Guan-Hua Du. "Pinocembrin protects rat brain against oxidation and apoptosis induced by ischemia–reperfusion both in vivo and in vitro," Brain Research, vol.1216, no.24, Jun 2008,p.104–115.

DOI: 10.1016/j.brainres.2008.03.049

Google Scholar

[13] Hwang, J.J., Choi, S.-Y., Koh, J.Y. "The role of NADPH oxidase, neuronal nitric oxide synthase and poly(ADP ribose) polymerase in oxidative neuronal death induced in cortical cultures by brain-derived neurotrophic factor and neurotrophin-4/5," J Neurochem, vol.82, no.4, Aug 2002, p.894–902.

DOI: 10.1046/j.1471-4159.2002.01040.x

Google Scholar

[14] Honig, L.S., Rosenberg, R.N. "Apoptosis and neurologic disease," Am. J.Me , vol.108, no.4, March 2000, p.317–330.

Google Scholar