Effect of Pentoxifylline on Ischemia- induced Brain Damage and Spatial Memory Impairment in Rat | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 12، دوره 15، شماره 5، آذر 2012، صفحه 1083-1090 اصل مقاله (696.42 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2012.4923 | ||
| نویسندگان | ||
| Shabnam Movassaghi1؛ Zahra Nadia Sharifi1؛ Mansooreh Soleimani2؛ Mohammad Taghi Joghataei2؛ Mehrdad Hashemi3؛ Hamed Shafaroodi4؛ Mehdi Mehdizadeh* 5، 2 | ||
| 1Anatomy Department, Tehran Medical Branch, Islamic Azad University, Tehran, Iran | ||
| 2Anatomy Department, Tehran University of Medical Sciences, Tehran, Iran | ||
| 3Genetic Department, Tehran Medical Branch, Islamic Azad University, Tehran, Iran | ||
| 4Pharmaceutical Science Branch & Pharmaceutical Science Research Centre, Islamic Azad University, Tehran, Iran | ||
| 5Cellular & Molecular Research Centre, Tehran University of Medical Sciences, Tehran, Iran | ||
| چکیده | ||
| Objective(s) The brief interruption of cerebral blood flow causes permanent brain damage and behavioral dysfunction. The hippocampus is highly vulnerable to ischemic insults, particularly the CA1 pyramidal cell layer. There is no effective pharmacological strategy for improving brain tissue damage induced by cerebral ischemia. Previous studies reported that pentoxifylline (PTX) has a neuroprotective effect on brain trauma. The possible neuroprotector effects of PTX on behavioral deficit were studied in male Wistar rats subjected to a model of transient global brain ischemia. Materials and Methods Animals (n= 32) were assigned to control, sham-operated, vehicle, and PTX- treated (200 mg/kg IP) groups. PTX administered at 1hr before and 3 hr after ischemia. Global cerebral ischemia was induced by bilateral common carotid artery occlusion, followed by reperfusion. Results Morris Water maze testing revealed that PTX administration in cerebral ischemia significantly improved hippocampal-dependent memory and cognitive spatial abilities after reperfusion as compared to sham-operated and vehicle-treated animals. After the behavioral test, the rats were sacrificed and brain sections were stained with Nissl staining. There were no significant differences between number of pyramidal cells in both control and PTX groups. Conclusion Our study demonstrated that pentoxifylline had a protective effect on rats with transient global ischemia and could reduce cognitive impairment. | ||
| کلیدواژهها | ||
| Neuroprotective؛ Pentoxifylline؛ Spatial Memory؛ Transient Ischemia | ||
| مراجع | ||
|
1.Diener HC. Empfehlungen für die Einrichtung von Schlaganfallspezial-stationen (Stroke units). Act Neurol 1996; 23:171-175.
2. Nagahiro S, Uno M, Sato K, Goto S, Morioka M, Ushio Y. Pathophysiology and treatment of cerebral ischemia. J Med Invest 1998; 45:57-70.
3. Wolf PA, Kannel WB, D’Agostino RB. Epidemiology of Stroke. In: Ginsberg MD, Bogousslavsky J.editors. Cerebrovascular disease: pathophysiology, diagnosis, and management. Massachusetts:Blackwell Science, Malden;1998.p.834-849.
4. Broderick J, Brott T, Kothari R, Miller R, Khoury J, Pancioli A, et al. The greater cincinnati/northern kentucky stroke study: preliminary first ever and total incidence rates of stroke among blacks. Stroke 1998; 29:415-451.
5. Dietrich WD. Neurobiology of stroke. Int Rev Neurobiol 1998; 42:55-101.
6. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischemic stroke: an integrated view. Trends Neurosci 1999; 22:391-397.
7. Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999; 79:1431-1568.
8. Snider BJ, Gottron FJ, Choi DW. Apoptosis and necrosis in cerebrovascular disease. Ann N Y Acad Sci 1999; 893:243-253.
9. Li RC, Guo SZ, Lee SK, Gozal D . Neuroglobin protects neurons against oxidative stress in global ischemia. J Cereb Blood Flow Metab. 2010; 30:1874-1882.
10.Cummings JL, Tomiyasu U, Read S, Benson DF. Amnesia with hippocampal lesions after cardiopulmonary arrest. Neurology 1984; 34:679–681.
11.Zola-Morgan S, Squire LR, Amaral DG. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the Hippocampus. J Neurosci 1986; 6:2950–2967.
12.Petito CK, Feldmann E, Pulsinelli WA, Plum F. Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology 1987; 37:1281–1286.
13.Pulsinelli WA, Brierley JB. A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 1979; 10:267–272.
14.Pulsinelli WA, Buchan AM. The four-vessel occlusion rat model method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke 1988; 19:913–914.
15.Hachinski V. Relevance of stroke models of stroke. Arch Neurol 1996 ;53:1308.
16.Grotta J. The current status of neuronal protective therapy: why have all neuronal protective drugs worked in animals but none so far in stroke patients? Cerebrovasc Dis 1994; 4:115-120.
17.The European Ad Hoc Consensus G: Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc Consensus Group Meeting. Cerebrovasc Dis 1998; 8:59-72.
18.Seiffge D. Pentoxifylline: its influence on interaction of blood cells with the vessel wall. Atherosclerosis 1997; 131:27–28.
19.Windmeier C, Gressner AM. Pharmacological aspects of pentoxifylline with emphasis on its inhibitory actions on hepatic fibrogenesis. Gen Pharmacol 1997; 29: 181–196.
20.Teixeira MM, Gristwood RW, Cooper N, Hellewell PG. Phosphodiesterase (PDE)4 inhibitors: anti-inflammatory drugs for the future Trends Pharmacol Sci 1997; 18:164–170.
21.Laurat E, Poirier B, Tupin E, Caligiuri G, Hansson GK, Bariety J, et al. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice. Circulation 2001; 194:197–202.
22.Haddad JJ, Land SC, Tarnow-Mordi WO, Zembala M, Kowalczyk D, Lauterbach R. Immunopharmacological potential of selective phosphodiesterase inhibition. I. Differential regulation of lipopolysaccharide-mediated proinflammatory cytokine (interleukin-6 and tumor necrosis factor-alpha) biosynthesis in alveolar epithelial cells. J Pharmacol Exp Ther 2002; 300:559–566.
23.Gutierrez M, Diez Tejedor E, Alonso de Leciñana M, Fuentes B, Carceller F, Roda JM. Thrombolysis and neuroprotection in cerebral ischemia. Cerebrovasc Dis 2006; 2:118–126.
24.Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS. The renoprotective potential of pentoxifylline in chronic kidney disease. J Chin Med Assoc 2004; 68: 99–105.
25.Navashiro H, Martin D, Hallenbeck JM. Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J Cereb Blood Flow Metab 1997; 17:229–232.
26.Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, et al. Tumor necrosis factoralpha. A mediator of focal ischemic brain injury. Stroke 1997; 28: 1233–1244.
27.Toung TJ, Kirsch JR, Maruki Y, Traystman RJ. Effects of pentoxifylline on cerebral blood flow, metabolism, and evoked response after total cerebral ischemia in dogs. Crit Care Med 1994; 22:273–281.
28.Kim KB, Jeon GH, Kim YR, Lee JH, Lee KH, Eun BL, et al. The effect of pentoxifylline on IL-1 beta and TNF-alpha mRNA gene expression in hypoxic-ischemic brain injury of immature rat. J Korean Child Neurol Soc? 1999; 7:181–187.
29.Evans SM, Pinto Pereira LM, Addae JI. Neuroprotection by caffeine and pentoxifylline during cerebral ischaemia. West Indian Med J 1999; 48:23–25.
30.Xu D, Bureau Y, McIntyre DC, Nicholson DW, Liston P, Zhu Y, et al. Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus. J Neurosci 1999; 19:5026-5033.
31.Tanabe M, Watanabe T, Ishibashi M, Hirano N, Tabuchi S, Takigawa H. Hippocampal ischemia in a patient who experienced transient global amnesia after undergoing cerebral angiography. Case illustration. J Neurosurg 1999; 91:347.
32.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.
33.Bendel O, Bueters T, von Euler M, Ögren SO, Sandin J, von Euler G. Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory. J Cereb Blood Flow Metab 2005; 25:1586–1595.
34.von Euler M, Bendel O, Bueters T, Sandin J, von Euler G. Profound but transient deficits in learning and memory after global ischemia using novel water maze test. Behav Brain Res 2006; 166:204–210.
35.Sugawara T, Chan PH. Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Antioxid Redox Signal 2003; 5:597–607.
36.Zhang YB, Kan MY, Yanga ZH, Dingc WL, Yid J, Chena HZ, et al. Neuroprotective effects of N-stearoyltyrosine on transient global cerebral ischemia in gerbils. Brain Res 2009; 1287:55-64.
37.Eun BL, Liu XH, Barks JD. Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats. Pediatr Res 2000; 47:73–78.
38.Banfi C, Sironi L, De Simoni G, Gelosa P, Barcella S, Perego C, et al. Pentoxifylline prevents spontaneous brain ischemia in stroke-prone rats. J Pharmacol Exp Ther 2004; 310:890–895.
39.Sliwa K, Woodiwiss A, Candy G, Badenhorst D, Libhaber C, Norton G, et al. Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 2002; 90:1118–1122.
40.Ji Q, Zhang L, Jia H, Xu J. Pentoxifylline inhibits endotoxin-induced NF-Kappa B activation and associated production of proinflammatory cytokines. Ann Clin Lab Sci 2004; 34:427–436.
41.Zhang M, Xu YJ, Saini HK, Turan B, Liu PP, Dhalla NS. Pentoxifylline attenuates cardiac dysfunction and reduces TNF-alpha level in ischemic-reperfused heart. Am J Physiol Heart Circ Physiol 2005; 289:H832–839.
42.Zhang M, Xu YJ, Saini HK, Turan B, Liu PP, Dhalla NS. TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload. Biochem Biophys Res Commun 2005; 327:57–63.
43.Davila-Esqueda ME, Martinez-Morales F. Pentoxifylline diminishes the oxidative damage to renal tissue induced by streptozotocin in the rat. Exp Diabesity Res 2004; 5:245–251.
44.Davila-Esqueda ME, Vertiz-Hernandez AA, Martinez-Morales F. Comparative analysis of the renoprotective effects of pentoxifylline and vitamin E on streptozotocin-induced diabetes mellitus. Ren Fail 2005; 27:115–122.
45.Radfar M, Larijani B, Hadjibabaie M, Rajabipour B, Mojtahedi A, Abdollahi M. Effects of pentoxifylline on oxidative stress and levels of EGF and NO in blood of diabetic type-2 patients: a randomized, double-blind placebo-controlled clinical trial. Biomed Pharmacother 2005; 59:302–306.
46.Myers SI, Horton JW, Hernandez R, Walker PB, Vaughan WG. Pentoxifylline protects splanchnic prostacyclin synthesis during mesenteric ischemia/reperfusion. Prostaglandins 1994; 47:137–150.
47.Schermuly RT, Roehl A, Weissmann N, Ghofrani HA, Leuchte H, Grimminger F, et al. Combination of nonspecific PDE inhibitors with inhaled prostacyclin in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2001; 281: L1361–L1368.
48. Strieter RM, Remick DG, Ward PA, Spengler RN, Lynch JP, 3rd Larrick J, et al. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun 1988; 155:1230–1236.
49.Guggilam A, Haque M, Kerut EK, McIlwain E, Lucchesi P, Seghal I, et al. TNF-alpha blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats. Am J Physiol Heart Circ Physiol 2007; 293:H599-609.
50.Sirin BH, Yilik L, Coskun E, Ortac R, Sirin H. Pentoxifylline reduces injury of the brain in transient ischemia. Acta Cardiol 1998; 53:89–95.
51.Bruno Rde B, Marques TF, Batista TM, Lima JC, de Arruda KG, Lima PF, et al. Pentoxifylline treatment improves neurological and neurochemical deficits in rats subjected to transient brain ischemia. Brain Res 2009; 1260:55-64. | ||
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