Skip to main content

Advertisement

Log in

Alpha-tocopherol in the brain tissue preservation of stroke-prone spontaneously hypertensive rats

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Oxidative stress has an important role in neuronal damage during cerebral ischemia and can lead to cognitive and behavioral impairment. Alpha-tocopherol, a powerful antioxidant, may be able to preserve neuronal tissue and circumvent neurological deficits. Thus, this study aimed to investigate the influence of alpha-tocopherol in the preservation of brain tissue and the maintenance of memory formation in stroke-prone spontaneously hypertensive rats (SHRSP). To achieve this aim, twenty-four 15-week-old male SHRSP rats were separated into the following four groups (n = 6 each) that received different treatments over a 4-week period: the alpha-tocopherol group, the control group, the L-NAME group, and the L-NAME + alpha-tocopherol group. We evaluated the physiological parameters (body weight, diuresis, and food and water intake), an oxidative stress marker (malondialdehyde levels), and neurological responses (the Morris Water Maze and Novel Objects Recognition tests). Afterwards, the brains were removed for histopathological analysis and quantification of the number of cells in the hippocampus. Statistically, the alpha-tocopherol group demonstrated better results when compared to all groups. The data indicated a reduction in oxidative stress and the preservation of neurological responses in groups treated with alpha-tocopherol. In contrast, the L-NAME group exhibited increased malondialdehyde levels, impairment of neurological responses, and several hippocampus tissue injuries. The others groups exhibited nerve tissue changes that were restricted to the glial nodes. No significant alterations were observed in the physiologic parameters. Based on these findings, we suggest that alpha-tocopherol can prevent stroke, preserve the structure of the hippocampus, and maintain both memory and cognition functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Allami N, Javadi-Paydar N, Rayatnia F et al (2011) Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice. Eur J Pharmacol 650:240–248

    Article  CAS  PubMed  Google Scholar 

  2. Alzoubia KH, Khabourb OF, Rashida BA et al (2012) The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress. Behav Brain Res 226:205–210

    Article  Google Scholar 

  3. Aradillas E, Libon DJ, Schwartzman RJ (2011) Acute loss of spatial navigational skills in a case of a right posterior hippocampus stroke. J Neurol Sci 308(1–2):144–146

    Article  PubMed  Google Scholar 

  4. Azzi A, Ricciarelli R, Zingg JM (2002) Non-antioxidant molecular functions of alpha-tocopherol (vitamin E). FEBS Lett 519:8–10

    Article  CAS  PubMed  Google Scholar 

  5. Brijesh R, Ravindran GA (2007) Spiking neural network of the CA3 of the hippocampus can be a neural prosthesis for lost cognitive functions. Conf Proc IEEE Eng Med Biol Soc 4:755–758

    Google Scholar 

  6. Chen J, Zacharek A, Zhang C et al (2005) Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice. J Neurosci 25:2366–75

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Comin D, Gazarini L, Zanoni JN et al (2010) Vitamin E improves learning performance and changes the expression of nitric oxide-producing neurons in the brains of diabetic rats. Behav Brain Res 210:38–45

    Article  CAS  PubMed  Google Scholar 

  8. Crouzin N, Ferreira MC, Cohen-Solal C et al (2010) Neuroprotection induced by vitamin E against oxidative stress in hippocampal neurons: involvement of TRPV1 channels. Mol Nutr Food Res 54:496–505

    Article  CAS  PubMed  Google Scholar 

  9. Cuppini R, Ciaroni S, Cecchini T et al (2002) Tocopherols enhance neurogenesis in dentate gyrus of adult rats. Int J Vitam Nutr Res 72:170–6

    Article  CAS  PubMed  Google Scholar 

  10. Ducruet AF, Sosunov SA, Visovatti SH et al (2011) Paradoxical exacerbation of neuronal injury in reperfused stroke despite improved blood flow and reduced inflammation in early growth response-1 gene-deleted mice. Neurol Res 33:717–725

    Article  CAS  PubMed  Google Scholar 

  11. Emmrich P, Hahn J, Ogunlade V et al (2003) Neuropathological findings after cardiac surgery-retrospective study over 6 years. Z Kardiol 92:925–937

    Article  CAS  PubMed  Google Scholar 

  12. Faraji J, Metz GA, Sutherland RJ (2011) Stress after hippocampal stroke enhances spatial performance in rats. Physiol Behav 102(4):389–399

    Article  CAS  PubMed  Google Scholar 

  13. Ferri P, Cecchini T, Ambrogini P et al (2006) Alpha-tocopherol effects neuronal plasticity in adult rat dentate gyrus: the possible role of PKCdelta. J Neurobiol 66:793–810

    Article  CAS  PubMed  Google Scholar 

  14. Fredriksson K, Nordborg C, Kalimo H et al (1988) Cerebral microangiopathy in stroke-prone spontaneously hypertensive rats. An immunohistochemical and ultrastructural study. Acta Neuropathol 75:241–252

    Article  CAS  PubMed  Google Scholar 

  15. Furini CR, Rossato JI, Bitencourt LL et al (2010) Adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the consolidation of object recognition long-term memory. Hippocampus 20:672–683

    CAS  PubMed  Google Scholar 

  16. Harooni HE, Naghdi N, Sepehri H et al (2009) The role of hippocampal nitric oxide (NO) on learning and immediate, short- and long-term memory retrieval in inhibitory avoidance task in male adult rats. Behav Brain Res 201:166–172

    Article  CAS  PubMed  Google Scholar 

  17. Hernández-Pinto AM, Puebla-Jiménez L, Arilla-Ferreiro E (2009) Alpha-tocopherol decreases the somatostatin receptor-effector system and increases the cyclic AMP/cyclic AMP response element binding protein pathway in the rat dentate gyrus. Neuroscience 162:106–17

    Article  PubMed  Google Scholar 

  18. Izquierdo I, Medina J (1997) Memory formation: the sequence of biochemical events in the hippocampus and its connection to activity in other brain structures. Neurobiol Learn Mem 68:285–316

    Article  CAS  PubMed  Google Scholar 

  19. Kayden HJ, Traber MG (1993) Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res 34:343–358

    CAS  PubMed  Google Scholar 

  20. Kim EM, Elliot JJ, Hobson P et al (2009) Effects of intrahippocampal injections on memory in the rat and attenuation with vitamin E. Prog Neuropsychopharmacol Biol Psychiatry 33:945–51

    Article  CAS  PubMed  Google Scholar 

  21. Kishi T, Hirooka Y, Kimura Y (2004) Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation 109:2357–2362

    Article  CAS  PubMed  Google Scholar 

  22. Leinonen JS, Ahonen JP, Lönnrot K et al (2000) Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke. Stroke 31:33–9

    Article  CAS  PubMed  Google Scholar 

  23. Minami M, Togashi H, Koike Y (1985) Changes in ambulation and drinking behavior related to stroke in stroke-prone spontaneously hypertensive rats. Stroke 16:44–48

    Article  CAS  PubMed  Google Scholar 

  24. Morris RGM (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods II 47–60

    Google Scholar 

  25. Mumby D (2005) Object Recognition. In: Whishaw IQ, Kolb B (eds) The behavior of the laboratory rat, sect. 36. Oxford University Press, New York, pp 383–91

    Google Scholar 

  26. Murad LB, Guimarães MRM, Vianna LM (2011) Alpha-tocopherol protects against memory impairment caused by L-NAME and modulates the injury marker and blood coagulant parameters. Biofactors 37:315–22

    Article  CAS  PubMed  Google Scholar 

  27. Nikonenko AG, Radenovic L, Andjus PR et al (2009) Structural features of ischemic damage in the hippocampus. Anat Rec 292:1914–1921

    Article  CAS  Google Scholar 

  28. Raza SS, Khan MM, Ashafaq M et al (2011) Silymarin protects neurons from oxidative stress associated damages in focal cerebral ischemia: a behavioral, biochemical and immunohistological study in Wistar rats. J Neurol Sci 309:45–54

    Article  CAS  PubMed  Google Scholar 

  29. Ricciarelli R, Zingg JM, Azzi A (2002) The 80th anniversary of vitamin E: beyond its antioxidant properties. Biol Chem 383:457–465

    Article  CAS  PubMed  Google Scholar 

  30. Sato H, Takahashi T, Sumitani K et al (2010) Glucocorticoids generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. J Clin Biochem Nutr 47:224–232

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Schreiber S, Bueche CZ, Garz C et al (2012) The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cereb Blood Flow Metab 32(2):278–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Shimada IS, Borders A, Aronshtam A et al (2011) Proliferating reactive astrocytes are regulated by notch-1 in the peri-infarct area after stroke. Stroke 42:3231–3237

    Article  PubMed  Google Scholar 

  33. Snider BJ, Du C, Wei L et al (2001) Cycloheximide reduces infarct volume when administered up to 6 h after mild focal ischemia in rats. Brain Res 917:147–57

    Article  CAS  PubMed  Google Scholar 

  34. Sun L, Zhou W, Mueller C et al (2010) Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia. J Cereb Blood Flow Metab 30:1651–60

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Sunil AG, Kesavanarayanana KS, Kalaivania P et al (2011) Total oligomeric flavonoids of Cyperus rotundus ameliorates neurological deficits, excitotoxicity and behavioral alterations induced by cerebral ischemic–reperfusion injury in rats. Brain Res Bull 84:394–405

    Article  CAS  PubMed  Google Scholar 

  36. Watson SN, Risling TE, Hermann PM, Wildering WC (2012) Failure of delayed nonsynaptic neuronal plasticity underlies age-associated long-term associative memory impairment. BMC Neuroscience 13:103

    Article  PubMed Central  PubMed  Google Scholar 

  37. Wu A, Ying Z, Gomez-Pinilla F et al (2010) Vitamin E protects against oxidative damage and learning disability after mild traumatic brain injury in rats. Neurorehabil Neural Repair 24:290–298

    Article  PubMed Central  Google Scholar 

  38. Zucca S, Valenzuela CF (2010) Low concentrations of alcohol inhibit BDNF-dependent GABAergic plasticity via L-type Ca2+ channel inhibition in developing CA3 hippocampal pyramidal neurons. J Neurosci 30:6776–6781

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgment

All the authors contributed equally to this article. This work received support from the Brazilian national agencies for research and development CNPq and CAPES.

Conflict of interests

There were no conflicts of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leonardo Borges Murad.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murad, L.B., Guimarães, M.R.M., Paganelli, A. et al. Alpha-tocopherol in the brain tissue preservation of stroke-prone spontaneously hypertensive rats. J Physiol Biochem 70, 49–60 (2014). https://doi.org/10.1007/s13105-013-0279-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-013-0279-y

Keywords

Navigation