Protection of edravone on neurons and its effects on the expression of interleukin-lβ in juvenile rat hippocampus following status convulsion
WANG Hai-Ping, LI Guang-Qian
Department of Neurology, Sixth Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine/Hangzhou Children's Hospital, Hangzhou 310014, China. Email：lgqcn@yahoo.com.cn
Abstract OBJECTIVE: To study the possible protection of edaravone on neurons of the hippocampus after status convulsion (SC) and its effects on the expression of interleukin-1β (IL-lβ) in juvenile rats. METHODS: One hundred and ninety-five juvenile male Sprague-Dawley rats were randomly divided into three groups: SC, edaravone pretreatment and normal saline control (control group). Each group was subdivided into five groups sacrificed at 4, 12, 24, 48 and 72 hrs after SC induction. SC model was prepared using lithium-pilocarpine. The edaravone pretreatment group received edaravone by intraperitoneal injection once daily three days before convulsion induction. Histopathologic changes in the hippocampus were viewed under a light microscope and an electron microscope. Expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL). Expression of IL-lβ protein was determined by immunohistochemistry. RESULTS: Under the electron microscrope, a small quantity of neurons showed karyopycnosis and endocytoplasmic reticulum (ER) expanded remarkably 24 hrs after SC induction; at 48 hrs the ER expanding was alleviated somewhat but mitochomdria swelling was more severe. The edaravone pretreatment group showed less severe neuronal changes compared with the SC group under the microscopes. The TUNEL positive cells in the hippocampus of the SC group were significantly more than those of the control group 12 hrs, and peaked at 48 hrs after SC induction. The edaravone pretreatment group showed decreased TUNEL positive cells in the hippocampus compared with the SC group, although the positive cells were more than those in the control group between 12 and 48 hrs after SC induction. The immunohistochemistry assay demonstrated that the expression of IL-lβ in the hippocampus of the SC group increased significantly compared with that of the control group 12, 24, 48 and 72 hrs after SC induction. Edaravone pretreatment resulted in a significantly decreased IL-lβ expression in the hippocampus as compared with the SC group. CONCLUSIONS: Edaravone pretreatment may decrease the IL-1β expression and neuronal apoptosis in the hippocampus. This suggests that edaravone may have protective effects against the hippocampal damage caused by SC.［Chin J Contemp Pediatr, 2010, 12 (3):205-210］
WANG Hai-Ping,LI Guang-Qian. Protection of edravone on neurons and its effects on the expression of interleukin-lβ in juvenile rat hippocampus following status convulsion[J]. 中国当代儿科杂志, 2010, 12(3): 205-210.
WANG Hai-Ping,LI Guang-Qian. Protection of edravone on neurons and its effects on the expression of interleukin-lβ in juvenile rat hippocampus following status convulsion[J]. CJCP, 2010, 12(3): 205-210.
［1］Araújo IM, Gil JM, Carreira BP, Mohapel P, Petersen A, Pinheiro PS, et al. Calpain activation is involved in early caspase-independent neurodegeneration in the hippocampus following status epilepticus［J］. Neurochem, 2008, 105（3）：666-667.
［2］Vezzani A, Granata T. Brain inflammation in epilepsy：experimental and clinical evidence［J］. Epilepsia, 2005, 46（11）：1724-1743.
［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］André V, Dubé C, Francois J, Leroy C, Rigoulot MA, Roch C, et al.Pathogenesis and pharmacology of epilepsy in the lithium-pilocarpine model［J］.Epilepsia, 2007, 48（Suppl 5）：41-47.
［7］Dinarello CA.Immunological and inflammatory functions of the interleukin-1 family［J］. Annu Rev Immunol, 2009, 27：519-550.
［8］Li B, Mahmood A, Lu O, Wu H, Xiong Y, Qu C, et al. Simuastatin attenuates microglial cells and astrocyte activation and decreases interleukin-1 beta level after traumatic brain injury［J］. Neurosurgery, 2009, 65(1): 179-185.
［9］Hailer NP, Vogt C, Korf HW, Dehghani F. Interleukin-1beta exacerbates and interleukin-1 receptor antagonist attenuates neuronal injury and microglial activation after excitotoxic damage in organotypic hippocampal slice cultures［J］. Eur J Neurosci, 2005, 21（9）：2347-2360.
［10］Sayyah M, Beheshti S, Shokrgozar MA, Eslami-far A, Deljoo Z, Khabiri AR, et al. Antiepileptogenic and anticonvulsant activity of interleukin-1 beta in amygdala-kindled rats［J］. Exp Neuro, 2005, 191（1）：145-153.
［12］De Simoni MG, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F, et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus［J］. Eur J Neurosci, 2000, 12（7）：2623-2633.
［13］Patel HC, Ross FM, Heenan LE. Neurodegenerative actions of interleukin-1 in the rat brain are mediated through increases in seizure activity［J］. J Neurosci Res, 2006, 83（3）：385-391.
