Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

Document Type: Original Article

Authors

1 Physiology Research Center and Medicinal Plants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Biology, Sciences Faculty, Islamic Azad University, Izeh Branch, Izeh, Iran

3 Department of Biology, Sciences & Researches Branch, Islamic Azad University, Fars, Iran

4 Department of Physiology and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

5 Iranian Neurosciences Research Network and Neurosciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 Department of Pharmacology and Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

 

Objective(s):
Cerebral hypoperfusion/ischemia (CHI) is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE) on passive avoidance memory and long-term potentiation (LTP) after permanent bilateral common carotid arteries occlusion (2CCAO) in male adult rats.
 
Materials and Methods:
Thirty-two adult male Wistar rats were randomly divided into: 1) Sham+Veh, 2) Isch+Veh, 3) Sham+GSE, 4) Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL) was measured and LTP was recorded from hippocampal dentate gyrus (DG) after high frequency stimulation (HFS) in all rats.
Results:
We found that memory was significantly impaired in rats after CHI (P<0.001) concomitant with hippocampal LTP inhibition (P<0.05, P1 and LTP48 respectively). GSE treatment significantly improved memory impairment and increased hippocampal LTP in rats with 2CCAO.
Conclusion:
Our results in present study suggest that GSE exhibits therapeutic potential for short-and long-term memories as well as LTP in DG, which is most likely related at least in part to its antioxidative and free radical scavenging actions.

Keywords


1. Aliev G, Smith MA, Obrenovich ME, de la Torre JC, Perry G. Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Azheimer disease. Neurotox Res 2003;5:491-504.

2. Ni J, Ohta H, Matsumoto K, Watanabe H. Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res 1994;653:231-236.

3. Block F. Global ischemia and behavioural deficits. Prog Neurobiol 1999;58:279-295.

4. Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson's disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res 2008;33:2416-26.

5. Aviram M, Dornfeld L, Kaplan M, Coleman R, Gaitini D, Nitecki S, et al. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases:

studies in atherosclerotic mice and in humans. Drugs Exp Clin Res. 2002;28:49-62.

6. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001 ;158:195-198.

7. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, et al. 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 2000;71:1062-76.

8. Harukuni I, Bhardwaj A. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin 2006;24:1-21.

9. Cechetti F, Worm PV, Pereira LO, Siqueira IR, C AN. 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 2010;43:1178-1183.

10. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: a model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev 2007;54:162-180.

11. Pfleger CM, Wang J, Friedman L, Vittorino R, Conley LM, Ho L, et al. Grape-seed polyphenolic extract improves the eye phenotype in a Drosophila model of tauopathy. Int J Alzheimers Dis 2010;2010.

12. Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG. Cellular protection with proanthocyanidins derived from grape seeds. Ann N Y Acad Sci 2002;957:11.

13. Sreemantula S, Nammi S, Kolanukonda R, Koppula S, Boini KM. Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model. BMC Complement Altern Med 2005;5:1.

14. Andres-Lacueva C, Shukitt-Hale B, GalliR L, Jauregui O, Lamuela-RaventosR M, Joseph JA. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci. 2005;8:10.

15. Shukitt-Hale B, Carey A, Simon L, Mark D, Joseph J. Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 2006;22:8.

16. Shinno K, Zhang L, Eubanks JH, Carlen PL, Wallace MC. Transient ischemia induces an early decrease of synaptic transmission in CA1 neurons of rat hippocampus: electrophysiologic study in brain slices. J Cereb Blood Flow Metab 1997;17:955-966.

17. Karaaslan O, Ulusoy M, Kankaya Y, Tiftikcioglu Y, Kocer U, Kankaya D, et al. Protective effect of grape seed extract against ischaemia/reperfusion injury in a rat epigastricflap model. J Plast Reconstr Aesthet Surg 2010;63:6.

18. Wang Y, Thomas P, Zhong J, Bi F, Kosaraju S, Pollard A, et al. Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse. Neurotox Res 2009;15:12.

19. Hwang IK, Yoo KY, Kim DS, Jeong YK, Kim JD, Shin HK, et al. Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia. Life Sci 2004;75:1989-2001.

20. Badavi M, Mehrgerdi F, Sarkaki A, Naseri M, Dianat M. Effect of grape seed extract on lead induced hypertension and heart rate in rat. Pak J Biol Sci 2008 ;11:6.

21. Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle

cerebral artery occlusion in rats. Statistical validation. Stroke. 1995;26:627-34.

22. Wallace JE, Krauter EE, Campbell BA. Motor and reflexive behavior in the aging rat. J Gerontol. 1980; 35:364-70.

23. Saadipour K, Sarkaki A, Alaei H, Badavi M, Rahim F. Forced exercise improves passive avoidance memory in morphine-exposed rats. Pak J Biol Sci 2009;12:1206-1211.

24. Paxinos G, Waston V. The rat brain in stereotaxic coordinates. 6 ed. London: Academic press limited; 2006.

25. Gureviciene I, Ikonen S, Gurevicius K, Sarkaki A, van Groen T, Pussinen R, et al. Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice. Neurobiol Dis 2004;15:188-195.

26. Dahiya K, Aggarwal K, Seth S, Singh V, Sharma TK. Type 2 diabetes mellitus without vascular complications and ischemia modified albumin. Clin Lab 2010;56:187-190.

27. Saulle E, Centonze D, Martin AB, Moratalla R, Bernardi G, Calabresi P. Endogenous dopamine amplifies ischemic long-term potentiation via D1 receptors. Stroke. 2002 ;33:2978-2984.

28. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999;22:391-397.

29. Cavaglia M, Dombrowski SM, Drazba J, Vasanji A, Bokesch PM, Janigro D. Regional variation in brain capillary density and vascular response to ischemia. Brain Res 2001;910:81-93.

30. Banerjee AK, Mandal A, Chanda D, Chakraborti S. Oxidant, antioxidant and physical exercise. Mol Cell Biochem 2003;253:307-312.

31. Squire LR, Zola SM. Ischemic brain damage and memory impairment: a commentary. Hippocampus. 1996;6:546-552.

32. Floyd RA. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 1999;222:236-45.

33. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000;48:4581-9.

34. Davalos A, Shuaib A, Wahlgren NG. Neurotransmitters and pathophysiology of stroke: evidence for the release of

glutamate and other transmitters/mediators in animals and humans. J Stroke Cerebrovasc Dis 2000;2-8.

35. Chun HS, Kim JM, Choi EH, Chang N. Neuroprotective effects of several korean medicinal plants traditionally used for stroke remedy. J Med Food 2008;11:246-251.

36. Colbourne F, Li H, Buchan AM, Clemens JA. Continuing postischemic neuronal death in CA1: influence of ischemia duration and cytoprotective doses of NBQX and SNX-111 in rats. Stroke 1999;30:662-668.

37. Collingridge GL, Kehl SJ, McLennan H. The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol. 1983 Jan;334:19-31.

38. Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging. 2002; 23:719-35.

39. Gottlieb M, Wang Y, Teichberg VI. Blood-mediated scavenging of cerebrospinal fluid glutamate. J Neurochem. 2003 Oct;87(1):119-26.

40. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food 2003 Winter;6:291-299.

41. Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr. 2003;133:3275S-3284S.

42. Scalbert A, Johnson IT, Saltmarsh M. Polyphenols: antioxidants and beyond. Am J Clin Nutr 2005; 81:215S-217S.

43. Jamshidzadeh A, Baha-al-dini Baigi B, Aram M. The effects of grape seed and grape pomace extracts onspatial memory impairment induced by hyoscine in mice. J Med Plants Res 2010;4:6.

44.

Ahn SH, Kim HJ, Jeong I, Hong YJ, Kim MJ, Rhie DJ, et al. Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons. BMC Neurosci 2011; 12:78-88.

45. Charradi K, Elkahoui S, Karkouch I, Limam F, Hassine FB, Aouani E. Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat. Neurochem Res 2012; 37:2004–2013.