Effects of edravone on glial fibrillary acidic protein and interleukin-lβ expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion
WANG Hai-Ping, DENG Xiao-Long, LI Guang-Qian
Department of Neurology, Sixth Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine, Hangzhou 310014, China. Email: lgqcn@yahoo.com.cn
Abstract OBJECTIVE: To study the effects of edaravone on glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-lβ) expression and neuronal apoptosis in the juvenile rat hippocampus after status convulsion (SC). METHODS: One hundred and ninety-five juvenile male Sprague-Dawley (SD) rats were randomly divided into 3 groups: normal saline control and SC with and without edaravone treatment. Each of the 3 groups was further subdivided into subgroups sacrificed at 4, 12, 24, 48 and 72 hrs after SC (n=15). The SC model was prepared using lithium-pilocarpine. The expression of GFAP and IL-lβ protein was detected with immunohistochemistry methods. The neuronal apoptosis was observed by TdT-mediated dUTP nick end labeling (TUNEL). The hippocampal GFAP mRNA expression was detected by RT-PCR. RESULTS: The value of IOD of GFAP and IL-lβ positive cells measured by immunohistochemistry in the untreated SC group increased compared with the control group. Expression of GFAP and IL-lβ protein was significantly reduced in the edaravone treated SC group compared with the untreated SC group. RT-PCR showed the expression trend of GFAP mRNA was similar to that of protein. The TUNEL positive cells in the hippocampus CA1 in the untreated SC group increased significantly 12 hrs after SC and reached a peak at 48 hrs compared with the control group. The intervention with edaravone decreased significantly TUNEL positive cells between 12-48 hrs after SC, but the number of TUNEL positive cells in the intervention group remained significantly greater than in the control group. CONCLUSIONS: The expression of GFAP and IL-lβ in the hippocampus increases after SC in rats. Edaravone may decrease the expression of GFAP and IL-1β and reduce the number of neuronal apoptosis. These results suggest that edaravone may have protective effects against brain damage caused by SC.
WANG Hai-Ping,DENG Xiao-Long,LI Guang-Qian. Effects of edravone on glial fibrillary acidic protein and interleukin-lβ expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion[J]. 中国当代儿科杂志, 2011, 13(3): 231-235.
WANG Hai-Ping,DENG Xiao-Long,LI Guang-Qian. Effects of edravone on glial fibrillary acidic protein and interleukin-lβ expression and neuronal apoptosis in juvenile rat hippocampus after status convulsion[J]. CJCP, 2011, 13(3): 231-235.
［1］Henshall DC. Apoptosis signalling pathways in seizure-induced neuronal death and epilepsy［J］. Biochem Soc Trans, 2007, 35(Pt 2): 421-423.
［2］Sama MA, Mathis DM, Furman JL, Abdul HM, Artiushin IA, Kraner SD, et al. Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity［J］. J Biol Chem, 2008, 283(32): 21953-21964.
［3］Martinian L, Boer K, Middeldorp J, Hol EM, Sisodiya SM, Squier W, et al. Expression patterns of glial fibrillary acidic protein(GFAP)-delta in epilepsy-associated lesional pathologies［J］. Neuropathol Appl Neurobiol, 2009, 35(4): 394-405.
［4］Yasuoka N, Nakajima W, Ishida A , Takada G. Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats［J］. Brain Res Dev Brain Res, 2004, 151(1-2): 129-139.
［6］Ravizza T, Vezzani A. Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system［J］. Neuroscience, 2006, 137(1): 301-308.
［7］Ravizza T, Gagliardi B, Noé F, Boer K, Aronica E, Vezzani A. Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy［J］. Neurobiol Dis, 2008, 29（1）: 142-160.
［8］Balosso S, Maroso M, SanchezAlavez M, Ravizza T, Frasca A, Bartfai T, et al. A novel non-transcriptional pathway mediates the proconvulsive effects of interleukin-1beta［J］. Brain, 2008, 131(Pt 12): 3256-3265.
［9］Decker Y, McBean G, Godson C. Lipoxin A4 inhibits IL-1 beta-induced IL-8 and ICAM-1 expression in 1321N1 human astrocytoma cells［J］. Am J Physiol Cell Physiol, 2009, 296（6）: C1420-C1427.
［10］Patel HC, Boutin H, Allan SM. Interleukin-1 in the brain: mechanisms of action in acute neurodegeneration［J］. Ann N Y Acad Sci, 2003, 992: 39-47.
