FASUDIL HYDROCHLORIDE EFFECTS ON EAAT2 AND ROCK2 PROTEIN EXPRESSIONS IN RAT MODEL OF NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY.
- Department of pediatrics unit 1,First Affiliated Hospital of Jiamusi University.
- Professor and Head, Department of pediatrics unit 1, First Affiliated Hospital of Jiamusi University.
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Jiamusi University.
- School of Stomatology, Department of Orthodontics and Dentofacial Orthopedics, Second Affiliated Dental Hospital of Jiamusi University.
- Cite This Article as
- Corresponding Author
Objective: To evaluate fasudil effects on EAAT2 and ROCK2 protein expressions in rat model of neonatal hypoxic-ischemic brain damage (HIBD). Methodology: 144 Seven-day-old Wistar rats were randomly divided into sham, HIBD, and fasudil groups. Fasudil group were injected intraperitoneally with that compound. Rat brains at 2, 6,12, 24, 48 and 72 h after HIBD were collected to determine histopathological damage and the expression levels of EAAT2 and ROCK2 proteins selected as the average optical density (AOD).Results were reported as average (x)standard deviation (SD), and single-factor analysis of variance (ANOVA) was performed between the multiple groups. A value of P <0.05 was considered statistically significant. Results: Histopathological damage was reduced in fasudil groups compared with the untreated HIBD group. The expression of ROCK2 in the HIBD group was significantly higher than that in SHAM and fasudil groups at the same times. EAAT2 expression was significantly decreased in HIBD group. Fasudil increased that expression. Conclusion: Fasudil reduced expression of Rock2 and increased expression of EAAT2. The increase in the expression of EAAT2 constitutes one of the pathways by which fasudil acts and that can explain its neuroprotective effects. Nevertheless further investigation should be conducted to better understand the mechanism of action of fasudil in neuroprotection it could bring in this disease.
- Cousens S, Lawn JE, Zupan J. Four Million Neonatal Deaths: When? Where? Why? The Lancet. 2005;365(9462):891-900.
- Robertson CM, Perlman M. Follow-up of the term infant after hypoxic-ischemic encephalopathy. Paediatrics & child health. 2006;11(5):278.
- Levene M, Grindulis H, Sands C, Moore J. Comparison of two methods of predicting outcome in perinatal asphyxia. The Lancet. 1986;327(8472):67-69.
- Vannucci RC. Current and potentially new management strategies for perinatal hypoxic-ischemic encephalopathy. 1990;85(6):961-968.
- Cotten CM, Shankaran S. Hypothermia for hypoxic?ischemic encephalopathy. Expert review of obstetrics & gynecology. 2010;5(2):227-239.
- Kucukdereli H, Allen NJ, Lee AT, et al. Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proceedings of the National Academy of Sciences. 2011;108(32):E440-E449.
- Lau CL, Beart PM, O?Shea RD. Transportable and non-transportable inhibitors of L-glutamate uptake produce astrocytic stellation and increase EAAT2 cell surface expression. Neurochemical research. 2010;35(5):735-742.
- Gerald F. Combs, Jr. The vitamins fundamental aspect in nutrition and health, Third Edition, Elsevir Inc., Amsterdam. 2008;143.
- Zagami CJ, Beart PM, Wallis N, Nagley P, O\'shea RD. Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis. 2009;57(2):119-135.
- Lau C, O\'shea R, Broberg B, Bischof L, Beart P. The Rho kinase inhibitor Fasudil up‐regulates astrocytic glutamate transport subsequent to actin remodelling in murine cultured astrocytes. British journal of pharmacology. 2011;163(3):533-545.
- Ding J, Li Q-Y, Yu J-Z, et al. Fasudil, a Rho kinase inhibitor, drives mobilization of adult neural stem cells after hypoxia/reoxygenation injury in mice. Molecular and Cellular Neuroscience. 2010;43(2):201-208.
- Beart P, O\'shea R. Transporters for L‐glutamate: An update on their molecular pharmacology and pathological involvement. British journal of pharmacology. 2007;150(1):5-17.
- Hawkins RA, O\'kane RL, Simpson IA, Vina JR. Structure of the blood?brain barrier and its role in the transport of amino acids. The Journal of nutrition. 2006;136(1):218S-226S.
- R? DB, Boucraut J, Samuel D, Birman S, Goff KL, Had‐Aissouni L. Glutamate transport alteration triggers differentiation‐state selective oxidative death of cultured astrocytes: a mechanism different from excitotoxicity depending on intracellular GSH contents. Journal of neurochemistry. 2003;85(5):1159-1170.
- Voutsinos-Porche B, Bonvento G, Tanaka K, et al. Glial glutamate transporters mediate a functional metabolic crosstalk between neurons and astrocytes in the mouse developing cortex. 2003;37(2):275-286.
- Abe K, Misawa M. Astrocyte stellation induced by Rho kinase inhibitors in culture. Developmental brain research. 2003;143(1):99-104.
- Abd‐El‐Basset EM, Fedoroff S. Upregulation of F‐actin and α‐actinin in reactive astrocytes. Journal of neuroscience research. 1997;49(5):608-616.
[Ndefi A ntima Yadiswa Robert, Wang Xian He, Zhang Ya Li, Zhu Zhang Long, Raihan Kibria, Nalika Robai and Indranil Ghosh. (2017); FASUDIL HYDROCHLORIDE EFFECTS ON EAAT2 AND ROCK2 PROTEIN EXPRESSIONS IN RAT MODEL OF NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY. Int. J. of Adv. Res. 5 (4). 1674-1679] (ISSN 2320-5407). www.journalijar.com
Article DOI: 10.21474/IJAR01/3997 DOI URL: http://dx.doi.org/10.21474/IJAR01/3997
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