1Physiology Research Center, Dept. of Physiology, Ahvaz Jundishpur University of Medical Sciences, 61357-15794, P.O.Box: 45, Ahvaz-Iran. Telefax: +98-611-3738248
2Dept. of Physiology, Medicine Faculty, Ahvaz Jundishpur University of Medical Sciences, Ahvaz-Iran
3Dept. of Biology, faculty of Sciences, Islamic Azad University, Izeh branch, Izeh-Iran.
Objective: Estrogen deficit following menopause results in cognitive behaviors impairment. Severity of these impairments in menopause women suffer with cerebral hypo perfusion/ischemia (HI) cause the brain damage and neuronal death. This study aimed to evaluate the effects of pomegranate seed extract (PGSE) on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO) in ovariectomized (OVX) rats. Materials and Methods: Adult female Wistar rats were divided randomly into eight groups with 8 rats in each group: 1) Sham-operated for ovaries and 2CCAO (ShO); 2) OVX and sham operated for ischemia (OShI); 3-7) OVX with 2CCAO (OI) received PGSE (100, 200, 400 and 800 mg/2ml/kg or normal saline, orally) for 14 days (OI+E100, 200, 400, 800 or OI+Veh); 8) OShI received most effective dose of PGSE (200 and 400 mg/kg for passive and active avoidance memories respectively). Active and passive avoidance tasks were measured in Y-maze and two-way shuttle box respectively. Data were analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. Results: Sensorimotor impaired in OShI+Veh and OI+Veh (P
Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. 2008. Role of nitric oxide synthases in Parkinson's disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res, 33: 2416-2426.
Aviram M, Dornfeld L. 2001. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis, 158: 195-198.
Aviram M, Dornfeld L, Kaplan M, Coleman R, Gaitini D, Nitecki S, Hofman A, Rosenblat M, Volkova N, Presser D, Attias J, Hayek, T, Fuhrman B. 2002. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp Clin Res, 28: 49-62.
Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. 2000. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr, 71: 1062-1076.
Banerjee A.K, Mandal A, Chanda D, Chakraborti S. 2003. Oxidant, antioxidant and physical exercise. Mol Cell Biochem, 253: 307-312.
Ben J, Soares FM, Scherer EB, Cechetti F, Netto CA, Wyse AT. 2010. Running exercise effects on spatial and avoidance tasks in ovariectomized rats. Neurobiol Learn Mem, 94: 312-317.
Ben Nasr C, Ayed N, Metche M. 1996. Quantitative determination of the polyphenolic content of pomegranate peel. Z Lebensm Unters Forsch, 203: 374-378.
Besnard S, Machado ML, Vignaux G, Boulouard M, Coquerel A, Bouet V, Freret T, Denise P, Lelong-Boulouard V. 2012. Influence of vestibular input on spatial and nonspatial memory and on hippocampal NMDA receptors. Hippocampus, 22: 814-826.
Block F. 1999. Global ischemia and behavioural deficits. Prog Neurobiol, 58: 279-295.
Canal Castro C, Pagnussat AS, Orlandi L, Worm P, Moura N, Etgen AM, Alexandre Netto C. 2012. Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats. Brain Res, 1474: 82-90.
Cechetti F, Pagnussat AS, Worm PV, Elsner VR, Ben J, da Costa MS, Mestriner R, Weis SN, Netto CA. 2012. Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment. Brain Res Bull, 87: 109-116.
Cechetti F, Worm PV, Pereira LO, Siqueira IR, C AN. 2010. The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate. Braz J Med Biol Res, 43: 1178-1183.
Choi DW, Rothman SM. 1990. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci, 13: 171-182.
Chun HS, Kim JM, Choi EH, Chang N. 2008. Neuroprotective effects of several korean medicinal plants traditionally used for stroke remedy. J Med Food, 11: 246-251.
Colbourne F, Li H, Buchan AM, Clemens, JA. 1999. Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke, 30: 662-668.
Collingridge GL, Kehl SJ, McLennan H. 1983. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol, 334: 19-31.
De Butte-Smith M, Zukin RS, Etgen AM. 2012. Effects of global ischemia and estradiol pretreatment on phosphorylation of Akt, CREB and STAT3 in hippocampal CA1 of young and middle-aged female rats. Brain Res, 1471: 118-128.
Dumlu MU, Gurkan E. 2007. Elemental and nutritional analysis of Punica granatum from Turkey. J Med Food, 10: 392-395.
Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. 2002. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging, 23: 719-735.
Evans PH. 1993. Free radicals in brain metabolism and pathology. Br Med Bull, 49, 577-587.
Garcia JH, Wagner S, Liu KF, Hu XJ. 1995. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke, 26: 627-634.
Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. 2000. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem, 48: 4581-4589.
Godino Mdel C, Romera VG, Sanchez-Tomero JA, Pacheco J, Canals S, Lerma J, Vivancos J, Moro MA, Torres M, Lizasoain I, Sanchez-Prieto J. 2013. Amelioration of ischemic brain damage by peritoneal dialysis. J Clin Invest, 123, 4359-4363.
Greenamyre JT, Olson JM, Penney JB, Jr, Young AB. 1985. Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites. J Pharmacol Exp Ther, 233: 254-263.
Hashimoto T, Yonetani M, Nakamura H. 2003. Selective brain hypothermia protects against hypoxic-ischemic injury in newborn rats by reducing hydroxyl radical production. Kobe J Med Sci, 49: 83-91.
Howard RS, Holmes PA, Siddiqui A, Treacher D, Tsiropoulos I, Koutroumanidis M. 2012. Hypoxic-ischaemic brain injury: imaging and neurophysiology abnormalities related to outcome. QJM, 105: 551-561.
Ito U, Spatz M, Walker JT, Jr, Klatzo I. 1975. Experimental cerebral ischemia in mongolian gerbils. I. Light microscopic observations. Acta Neuropathol, 32: 209-223.
Jee YS, Ko IG., Sung YH, Lee JW, Kim Y.S., Kim SE, Kim BK, Seo JH, Shin MS, Lee HH, Cho HJ, Kim CJ. 2008. Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin. Neurosci Lett, 443: 188-192.
Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, Aviram M. 2001. Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr, 131: 2082-2089.
Kaur A, Jindal S, Kaur IP, Chopra K. 2013. Effect of sesamol on the pathophysiological changes induced by surgical menopause in rodents. Climacteric, 16: 426-437.
Kim ND, Mehta R, Yu W, Neeman I, Livney T, Amichay A, Poirier D, Nicholls P, Kirby A, Jiang W, Mansel R, Ramachandran C, Rabi T, Kaplan B, Lansky E. 2002. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat, 71: 203-217.
Lau FC, Shukitt-Hale B, Joseph JA. 2005. The beneficial effects of fruit polyphenols on brain aging. Neurobiol Aging, 26Suppl 1: 128-132.
Lavenex P, Sugden SG, Davis RR, Gregg JP, Lavenex PB. 2011. Developmental regulation of gene expression and astrocytic processes may explain selective hippocampal vulnerability. Hippocampus, 21: 142-149.
Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Plum F. 1985. Predicting outcome from hypoxic-ischemic coma. JAMA, 253: 1420-1426.
Lipton SA, Rosenberg PA. 1994. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med, 330: 613-622.
Mahut H, Zola-Morgan S, Moss M. 1982. Hippocampal resections impair associative learning and recognition memory in the monkey. J Neurosci, 2: 1214-1220.
Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. 2013. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food chemistry, 138: 1028-1033.
McCarty MF. 2000. Up-regulation of endothelial nitric oxide activity as a central strategy for prevention of ischemic stroke - just say NO to stroke! Med Hypotheses, 55: 386-403.
Meyer FB, Sundt TM, Jr, Yanagihara T, Anderson RE. 1987. Focal cerebral ischemia: pathophysiologic mechanisms and rationale for future avenues of treatment. Mayo Clin Proc, 62: 35-55.
Navarro A, Del Valle E, Ordonez C, Martinez E, Perez C, Alonso A, Gonzalez C, Tolivia J. 2013. Aging and substitutive hormonal therapy influence in regional and subcellular distribution of ERalpha in female rat brain. Age (Dordr), 35: 821-837.
O'Keefe J, Conway DH. 1978. Hippocampal place units in the freely moving rat: why they fire where they fire. Exp Brain Res, 31: 573-590.
Pilsakova L, Riecansky I, Jagla F. 2010. The physiological actions of isoflavone phytoestrogens. Physiol Res, 59: 651-664.
Planton M, Peiffer S, Albucher JF, Barbeau EJ, Tardy J, Pastor J, Januel AC, Bezy C, Lemesle B, Puel M, Demonet JF, Chollet F, Pariente J. 2012. Neuropsychological outcome after a first symptomatic ischaemic stroke with 'good recovery'. Eur J Neurol, 19: 212-219.
Qu N, Wang L, Liu ZC, Tian Q, Zhang Q. 2013. Oestrogen receptor alpha agonist improved long-term ovariectomy-induced spatial cognition deficit in young rats. Int J Neuropsychopharmacol, 16: 1071-1082.
Rhodes ME, Frye CA. 2004. Estrogen has mnemonic-enhancing effects in the inhibitory avoidance task. Pharmacol Biochem Behav, 78: 551-558.
Sarkaki A, Badavi M, Hoseiny N, Gharibnaseri M, Rahim F. 2008. Postmenopausal effects of intrastriatal estrogen on catalepsy and pallidal electroencephalogram in an animal model of Parkinson's disease. Neuroscience, 154: 940-945.
Sarkaki A, Hajipour S, Mansouri MT, Pilevarian A, Rad MR. 2013a. Pomegranate seed hydroalcoholic extract improves memory deficit due to permanent cerebral hypoperfusion/ischemia in male rats. HealthMed, 7: 863-871.
Sarkaki A, Norooz Zare F, Farbood Y, Pileverian AA. 2013b. Impaired movements in 6-OHDA induced Parkinson's rat model improves by pomegranate seed hydroalcoholic extract. HealthMed, 7: 348-358.
Sarkaki A, Rezaiei M. 2013. Improving Active and Passive Avoidance Memories Deficits Due to Permanent Cerebral Ischemia by Pomegranate Seed Extract in Female Rats. The Malaysian journal of medical sciences: MJMS, 20: 25-35.
Schilling T, Ebert R, Raaijmakers N, Schutze, N, Jakob F. 2014. Effects of phytoestrogens and other plant-derived compounds on mesenchymal stem cells, bone maintenance and regeneration. The Journal of steroid biochemistry and molecular biology, 139: 252-261.
Scott EL, Zhang QG, Han D, Desai BN, Brann DW. 2013. Long-term estrogen deprivation leads to elevation of Dickkopf-1 and dysregulation of Wnt/beta-Catenin signaling in hippocampal CA1 neurons. Steroids, 78: 624-632.
Selvamani A, Sohrabji, F. 2010. The neurotoxic effects of estrogen on ischemic stroke in older female rats is associated with age-dependent loss of insulin-like growth factor-1. J Neurosci, 30: 6852-6861.
Sheorajpanday RV, Nagels G, Weeren AJ, van Putten MJ, De Deyn PP. 2011. Quantitative EEG in ischemic stroke: correlation with functional status after 6 months. Clin Neurophysiol, 122: 874-883.
Takeda A, Tamano H, Tochigi M, Oku N. 2005. Zinc homeostasis in the hippocampus of zinc-deficient young adult rats. Neurochem Int, 46: 221-225.
Tamburella A, Micale V, Mazzola C, Salomone S, Drago F. 2012. The selective norepinephrine reuptake inhibitor atomoxetine counteracts behavioral impairments in trimethyltin-intoxicated rats. Eur J Pharmacol, 683: 148-154.
van Elswijk, D.A., Schobel, U.P., Lansky, E.P., Irth, H. & van der Greef, J. (2004) Rapid dereplication of estrogenic compounds in pomegranate (Punica granatum) using on-line biochemical detection coupled to mass spectrometry. Phytochemistry, 65: 233-241.
Varadinova MG, Docheva-Drenska DI, Boyadjieva NI. 2009. Effects of anthocyanins on learning and memory of ovariectomized rats. Menopause,16: 345-349.
Yu X, Wang LN, Du QM, Ma L, Chen L, You R, Liu L, Ling JJ, Yang ZL, Ji H. 2012. Akebia Saponin D attenuates amyloid beta-induced cognitive deficits and inflammatory response in rats: Involvement of Akt/NF-kappaB pathway. Behav Brain Res, 235: 200-209.