Hypoxia, due to impaired cerebral blood flow, has hazardous effects on brain structure and function. To minimize as much as possible the neurological consequences from hypoxic-ischemic (HI) brain injury, neuro-protective strategies are urgently required. Vitamin E ha s been shown to have protective effects against cerebral ischemia, possibly due to its anti-oxidant effects. Thirty albino rats, of both sexes, were obtained from the animal house at King Khalid University Hospital , King Saud University . They were divided into three groups; each included 10 animals: Group A was considered as a control one, animals of Group B were subjected to a permanent link to the carotid arteries on both sides and animals of Group C underwent permanent link to carotid arteries on both sides and concomitantly were given Vitamin E as an anti-oxidant. Animals of Group C were injected by Vitamin E (equivalent to 15 mg/day), into the peritoneal cavity as a single dose for a week and after the prescribed period the mice were sacrificed under deep anesthesia and their brains were extracted and prepared for an electron microscopic study of brain tissue. Specimens from animals of Group B showed a large number of neurons that had been deteriorated. Mitochondria were the most affected organelles. There were a large number of dark cells which probably resulted from shrunken nerve cells and exhibited opaque nuclei. The number of affected nerve cells was much lower in brain tissues from animals of the Group C which revealed absence of dark cells. The study did not disclose any similar changes in brain tissues of the control group animals. Our results suggested that treatment with Vitamin E after hypoxia-ischemia led to a neuro-protective effect that appeared in reduction of cell death of neurons. Thus, the present study provides an evidence that Vitamin E protects the brain tissue of the consequences of hypoxia caused by ischemia in the tested experimental animals. It could be recommended in the treatment of cerebrovascular stroke and neurodegenerative diseases.
KeywordsHypoxiaVitamin EIschemia
R. A. Floyd, “Role of Oxygen Free Radicals in Carcinogenesis and Brain Ischemia,” FASEB Journal, Vol. 4, No. 9, 1990, pp. 2587-2597.
E. Shohami, E. Beit-Yannai, M. Horowitz and R. Kohen, “Oxidative Stress in Closed-Head Injury: Brain Antioxidant Capacity as an Indicator of Functional Outcome,” Journal of Cerebral Blood Flow and Metabolism, Vol. 17, No. 1997, pp. 1007-1019. doi:10.1097/00004647-199710000-00002
A. R. Green, A. H. Hainsworth and D. M. Jackson, “GABA Potentiation: A logical Pharmacological Approach for The Treatment of Acute Ischemic Stroke,” Neuropharmacology, Vol. 39, No. 9, 2000, pp. 1483-1494. doi:10.1016/S0028-3908(99)00233-6
N. R. Sims and E. Zaidan, “Biochemical Changes Associated with Selective Neuronal Death Following Short-Term Cerebral Ischaemia,” International Journal of Biochemistry & Cell Biology, Vol. 27, No. 6, 1995, pp. 531-550. doi:10.1016/1357-2725(95)00026-L
S. H. Rezkalla and R. A. Kloner, “No-Reflow Phenomenon,” Circulation, Vol. 105, 2002, pp. 656-662. doi:10.1161/hc0502.102867
K. Yamagata, T. Kitazawa, M. Shinoda, C. Tagawa, M. Chino and H. Matsufuji, “Stroke Status Evoked Adhesion,” Stroke Research and Treatment, Vol. 2010, 2010, pp. 11-17.
J. C. Dekkers, L. J. P. van Doornen and H. C. G. Kemper, “The Role of Antioxidant Vitamins and Enzymes in the Prevention of Exercise-Induced Muscle Damage,” Sports Medicine, Vol. 21, No. 3, 1996, pp. 213-238.
M. Tagami, K. Yamagata, K. Ikeda, Y. Nara, H. Fujino, A. Kubota, F. Numano and Y. Yamori, “Vitamin E Prevents Apoptosis in Cortical Neurons during Hypoxia and Oxygen Reperfusion,” Nature Publishing, New York, 1998, pp. 1415-1429.
M. Kaczmarski, J. Wojicicki, L. Samochowiee, T. Dutkiewicz and Z. Sych, “The Influence of Exogenous Antioxidants and Physical Exercise on Some Parameters Associated with Production and Removal of Free Radicals,” Pharmazie, Vol. 54, No. 4, 1999, pp. 303-306.
S. D. Bartolome, A. J. Casillan, J. G. Wood, S. Q. Simpson and A. R. O’Brien-Ladner, “Activated Protein C Infusion Mimics Antioxidant Effects on Hypoxia-Induced Microvascular Injury,” Chest, Vol. 128, No. 4, 2005, p. 377S.
S. Inci, O. E. Ozcan and K. Kilincx, “Time-Level Relationship for Lipid Peroxidation and the Protective Effect of Alpha-Tocopherol in Experimental Mild and Severe Brain Injury,” Neurosurgery, Vol. 43, No. 2, 1998, pp. 330-335. doi:10.1097/00006123-199808000-00095
M. G. Traber, “Vitamin E.” In: M. E. Shils, M. Shike, A. C. Ross, B. Caballero and R. Cousins, Eds., Modern Nutrition in Health and Disease, 10th Edition, Lippincott Williams & Wilkins, Baltimore, 2006, pp. 396-411.
G. Leonarduzzi, B. Sottero and G. Poli, “Targeting Tissue Oxidative Damage by Means of Cell Signaling Modulators: The Antioxidant Concept Revisited,” Pharmacology & Therapeutics, Vol. 128, No. 2, 2010, pp. 336-374. doi:10.1016/j.pharmthera.2010.08.003
K. Jomova, D. Vondrakova, M. Lawson and M. Valko, “Metals Oxidative Stress and Neurodegenerative Disorders,” Molecular and Cellular Biochemistry, Vol. 345, No. 1-2, 2010, pp. 91-104.
P. Lipton, “Ischemic Cell Death in Brain Neurons,” Physiological Reviews, Vol. 79, No. 4, 1999, pp. 1-33.
D. S. Warner, H. Sheng and I. Batinie-Haberle, “Oxidants, Antioxidants and the Ischemic Brain,” Journal of Experimental Biology, Vol. 207, 2004, pp. 3221-3231. doi:10.1242/jeb.01022
M. M. El Kossi and M. M. Zakhary, “Oxidative Stress in the Context of Acute Cerebrovascular Stroke,” Stroke, Vol. 31, No. 8, 2000, pp. 1889-1892.
A. L. Edinger and C. B. Thompson, “Death by Design: Apoptosis, Necrosis and Autophagy,” Current Opinion in Cell Biology, Vol. 16, No. 6, 2004, pp. 663-669. doi:10.1016/j.ceb.2004.09.011
Y. Tsujimoto and S. Shimizu, “Another Way to Die: Autophagic Programmed,” US Department of Agriculture, Agricultural Research Service, USDA National Nutrient Database for Standard Reference, 2004.
F. Adhami, G. H. Liao, Y. M. Morozov, A. Schloemer, V. J. Schmithorst, J. N. Lorenz, R. S. Dunn, C. V. Vorhees, M. Wills-Karp, J. L. Degen, R. J. Davis, N. Mizushima, P. Rakic, B. J. Dardzinski, S. K. Holland, F. R. Sharp and C.-Y. Kuan, “Cerebral Ischemia-Hypoxia Induces Intravascular Coagulation and Autophagy,” American Journal of Pathology, Vol. 169, No. 2, 2006, pp. 566-583. doi:10.2353/ajpath.2006.051066
M. R. Pulera, L. M. Adams, H. T. Liu and D. G. Santos, National Institutes of Health Office of Dietary Supplements Bethesda, Maryland, 1998. http://ods.od.nih.gov/
T. Kirino, “Delayed Neuronal Death in the Gerbil Hippocampus Following Ischemia,” Brain Research, Vol. 239, No. 1, 1982, pp. 57-69. doi:10.1016/0006-8993(82)90833-2
J. C. Baron, “Perfusion Thresholds in Human Cerebral Ischemia: Historical Perspective and Therapeutic Implications,” Cerebrovascular Diseases, Vol. 11, Suppl. 1, 2001, pp. S2-S8. doi:10.1159/000049119
J. Sobesky, O. Zaro Weber, F. G. Lehnhardt, V. Hesselmann, M. Neveling, A. Jacobs and W. D. Heiss, “Does the Mismatch Match the Penumbra? Magnetic Resonance Imaging and Positron Emission Tomography in Early Ischemic Stroke,” Stroke, Vol. 36, 2005, pp. 980-985. doi:10.1161/01. STR.0000160751.79241.a3
B. Levine and D. J. Klionsky, “Development by Self-Digestion: Molecular Mechanisms and Biological Functions of Autophagy,” Developmental Cell, Vol. 6, No. 4, 2004, pp. 463-477. doi:10.1016/S1534-5807(04)00099-1
P. G. Clarke, “Developmental Cell Death: Morphological Diversity and Multiple Mechanisms,” Anatomy and Embryology, Vol. 181, No. 3, 1990, pp. 195-213. doi:10.1007/BF00174615
M. Sano, C. Ernesto, R. G. Thomas, M. R. Klauber, K. Schafer and M. Grundman, “A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzehimers Disease,” New England Journal of Medicine, Vol. 336, 1997, pp. 1216-1222. doi:10.1056/NEJM199704243361704
E. M. Grahama, O. P. Mishrab and M. Delivoria-Papadopoulosb, “Anti-Oxidants and Oxidative Stress Injuries to the Brain in the Perinatal Period,” Seminars in Neonatology, Vol. 3, No. 2, 1998, pp. 75-85.
M. E. Raichle, “The Pathophysiology of Brain Ischemia,” Annals of Neurology, Vol. 13, No. 1, 1983, pp. 2-10. doi:10.1002/ana.410130103
M. Tagami, K. Ikeda, K. Yamagata, Y. Nara, H. Fujino, A. Kubota, F. Numano and Y. Yamori, “Vitamin E Prevents Apoptosis in Hippocampal Neurons Caused by Cerebral Ischemia and Reperfusion in Stroke-Prone Spontaneously Hypertensive Rats,” Laboratory Investigation, Vol. 79, No. 5, 1999, pp. 609-615.
Y. F. Franz, W. P. Tsang and T. T. Kwok, “Antioxidant Suppression of Apoptosis Induction by Re-Oxygenation after Chronic Hypoxia in Human Hepatocellular HepG2 Cells,” Proceedings of the American Association for Cancer Research, Vol. 47, 2003.
M. G. Traber, “Vitamin E Regulatory Mechanisms,” Annual Review of Nutrition, Vol. 27, 2007, pp. 347-362. doi:10.1146/annurev.nutr.27.061406.093819
K. Ikeda, H. Negishib and Y. Yamoric, “Antioxidant Nutrients and Hypoxia/Ischemia Brain Injury in Rodents,” Toxicology, Vol. 189, No. 1-2, 2003, pp. 55-61.
S. F. Yan, N. Mackman, W. Kisiel, D. M. Stern and D. J. Pinsky, “Hypoxia/Hypoxemia-Induced Activation of the Pro-Coagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 19, 1999, pp. 2029-2035. doi:10.1161/01.ATV.19.9.2029
V. S. Ten and D. J. Pinsky, “Endothelial Response to Hypoxia: Physiologic Adaptation and Pathologic Dysfunction,” Current Opinion in Critical Care, Vol. 8, No. 3, 2002, pp. 242-250. doi:10.1097/00075198-200206000-00008
R. J. Glynn, P. M. Ridker, S. Z. Goldhaber, R. Y. Zee and J. E. Buring, “Effects of Random Allocation to Vitamin E Supplementation on The Occurrence of Venous Thrombo-Embolism: Report from the Women’s Health Study,” Circulation, Vol. 116, 2007, pp. 1497-1503. doi:10.1161/CIRCULA TIONAHA.107.716407