Skip to main content
SpringerLink
Log in

Neuroprotective effect of Spirulina in cerebral ischemia–reperfusion injury in rats

  • Basic Neurosciences, Genetics and Immunology - Original Paper
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Epidemiological studies indicate that the intake of Mediterranean-style diet is inversely associated with risk of stroke, cardiovascular diseases, and cancer. Spirulina is widely used nutritional supplement rich in proteins and antioxidants. Evidence demonstrates that the impaired energy metabolism and the excessive generation of reactive oxygen radicals contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effect of Spirulina was investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia–reperfusion injury in rats. Male albino rats were divided into six groups: control, sham-operated group, ischemic control group, and Spirulina-pretreated groups (45, 90 and 180 mg/kg/p.o.). Spirulina was administered once a day, for 7 days. The rats were subjected to a 2-h right MCAO via the intraluminal filament technique and 22 h of reperfusion. Pretreatment with Spirulina significantly reduced the histological changes and neurological deficits. Spirulina at a dose of 180 mg/kg significantly reversed the elevated brain malondialdehyde (MDA) content and restored the decreased activities of brain superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) indicating that Spirulina has the protective potential against cerebral ischemia injury and its protective effects may be due to its antioxidant property.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  • Aebi H (1984) Catalase. Methods Enzymol 105:125–126

    Google Scholar 

  • Bains JS, Shaw CA (1997) Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Rev 25:335–338

    Article  CAS  PubMed  Google Scholar 

  • Baker K, Marcus CB, Huffman K, Kruk H, Malfori B, Doctrow SR (1998) Synthetic combined superoxide dismutase/catalase mimetics are protective as a delayed treatment in a rat stroke model: a key role for reactive oxygen species in ischemic brain injury. J Pharmacol Exp Ther 284:215–221

    CAS  PubMed  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1992) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624

    Article  Google Scholar 

  • Belayev L, Busto R, Zhao W, Ginsberg MD (1995) HU-211, a novel noncompetitive N-methyl-d aspartate antagonist, improves neurological deficit and reduces infarct volume after reperfusion injury in the rat. Stroke 26:2313–2320

    CAS  PubMed  Google Scholar 

  • Bhandari U, Ansari NM (2008) Protective effect of aqueous extract of Embelia ribes Burm fruits in mid cerebral ischemia in rats. Indian J Pharmacol 40:215–220

    Article  PubMed  Google Scholar 

  • Bhat VB, Madyastha KM (2000) C-phycocyanin: a potent peroxylradical scavenger in vivo and in vitro. Biochem Biophys Res Commun 275(1):20–25

    Article  CAS  PubMed  Google Scholar 

  • Bhat VB, Madyastha KM (2001) Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina plantensis: protection against oxidative damage to DNA. Biochem Biophys Res Commun 285:262–266

    Article  CAS  PubMed  Google Scholar 

  • Bickford PC, Gould T, Briederick L, Chadman K, Pollock A, Young D, Shukitt-Hale B, Joseph J (2000) Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats. Brain Res 866:211–217

    Article  CAS  PubMed  Google Scholar 

  • Bolokadze N, Lobjanidze I, Momtselidze N, Solomonia R, Shakarishvili R (2004) Blood rheological properties and lipid peroxidation in cerebral and systemic circulation of neurocritical patients. Clin Hemorheol Microcirc 30:99–105

    CAS  PubMed  Google Scholar 

  • Cano CP, Bermudez VP, Atencio HE, Medina MT, Anilsa A (2003) Increased serum malondialdehyde and decreased nitric oxide within 24 hours of thrombotic stroke onset. Am J Ther 10:473–476

    Article  PubMed  Google Scholar 

  • Cao W, Carney JM, Duchon A, Floyd RA, Chevion M (1998) Oxygen free radical involvement in ischemia and reperfusion injury to brain. Neurosci Lett 88:233–238

    Article  Google Scholar 

  • Careri M, Furlattini L, Mangia A, Musc M, Anklam E, Theobald A, Holst Von (2001) Supercritical fluid extraction for liquid chromatographic determination of carotenoids in spirulina pacifica algae: a chemometric approach. J Chromatogr A 912:61–71

    Article  CAS  PubMed  Google Scholar 

  • Clark WM, Rinker LG, Lessov NS, Lowery SL, Cipolla MJ (2001) Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 32:1000–1004

    CAS  PubMed  Google Scholar 

  • Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate and neurodegenerative disorders. Science 262:689–695

    Article  CAS  PubMed  Google Scholar 

  • Cross CE, Halliwell B, Borish ET, Pryor WA, Ames BN, Saus RL (1987) Oxygen radicals and human disease. Ann Intern Med 107:526–545

    CAS  PubMed  Google Scholar 

  • Delanty LN, Dichter MA (1998) Oxidative injury in the nervous system. Arch Neurol Scand 98:145–153

    Article  CAS  Google Scholar 

  • Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371

  • Duval C, Poelman M (1994) Scavenger effect of vitamin E and derivatives on free radicals generated by photo irradiated phenomelanin. J Pharm Sci 84:107–110

    Article  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • Farbiszewski R, Bielawski K, Bielawska A, Sobaniec W (1995) Spermine protects in vivo the anti-oxidant enzymes in transiently hypoperfused rat brain. Acta Neurobiol Expermentalis 55:253–258

    CAS  Google Scholar 

  • Foote CF, Denny RW (1968) Chemistry of singlet oxygen. VII. Quenching by b-carotene. J Am Chem Soc 90:6233–6235

    Article  CAS  Google Scholar 

  • Foote CF, Chang YC, Denny RW (1970) Chemistry of singlet oxygen. X. Carotenoids quenching parallels biological protection. J Am Chem Soc 92:5216–5219

    Article  CAS  PubMed  Google Scholar 

  • Fujimura M, Morita-Fujimura Y, Noshita N, Sugawara T, Kawase M, Chan PH (2000) The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice. J Neurosci 20:2817–2824

    CAS  PubMed  Google Scholar 

  • Gariballa SE, Hutchin TP, Sinclair AJ (2002) Antioxidant capacity after acute ischaemic stroke. QJM 95:685–690

    Article  CAS  PubMed  Google Scholar 

  • Gemma C, Mesches MH, Sepesi B, Choo K, Holmes DB, Bickford PC (2002) Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar-adrenergic function and increases in proinflammatory cytokines. J Neurosci 22:6114–6120

    CAS  PubMed  Google Scholar 

  • Gerster H (1993) Anticarcinogenic effect of common carotenoids. Int J Vitam Nutr Res 63:93–121

    CAS  PubMed  Google Scholar 

  • Globus MY, Alonsa O, Dietrich WD, Busto R, Ginseberg MD (1995) Glutamate release and free radical production following brain injury: effect of posttraumatic hypothermia. J Neurochem 65:1704–1711

    Article  CAS  PubMed  Google Scholar 

  • Gringo JM (1997) Reperfusion injury. Transplant proc 29:59–61

    Article  Google Scholar 

  • Gupta YK, Briyal S (2004) Animal models of cerebral ischemia for evaluation of drugs. Indian J Physiol Pharmacol 48:379–394

    CAS  PubMed  Google Scholar 

  • Guptha R, Manjeet S, Ajay S (2003) Neuroprotective effect of antioxidants on ischemia-reperfusion induced cerebral injury. Pharmacol Res 48(2):209–215

    Google Scholar 

  • Halliwell B (1991) Reactive oxygen species in living system, source, biochemistry and role in human disease. Am J Med 99:145–225

    Google Scholar 

  • Henrikson R (1989) Earth food spirulina. Cited from Recolina Limited, Ronore Enterprises Inc., Launa Beach, CA, pp 27–65

    Google Scholar 

  • Hirata T, Tanaki M, Ooiki M, Tsunomura T, Sagachuchi M (2000) Antioxidant activities of Phycocyanobilin prepared from Spirulina platensis. J Appl Phycol 12:435–439

    Article  CAS  Google Scholar 

  • Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P (2000) Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Stroke 31:2301–2306

    CAS  PubMed  Google Scholar 

  • Hosseinzadeh H, Parvadeh S, Nassiri M, Hamid R, Sadgnia Ziaee T (2007) Effect of Thymoquinone and Nigella Sativa Seed oil on lipid peroxidation level during global cerebral ischemia reperfusion injury in rat hippocampus. Phyto Med 14(9):621–627

    Article  CAS  Google Scholar 

  • Hwang IK, Yoo K-Y, Kim DS, Jeong Y-K, Kim JD, Shin H-K, Lim SS, Yoo I-D, Kang T-C, Kim D-w, Moon W-K, Won MH (2004) Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia. Life Sci 75:1989–2001

    Article  CAS  PubMed  Google Scholar 

  • Jenner P (1994) Oxidative damage in neurodegenerating diseases. Lancet 344:796–798

    Article  CAS  PubMed  Google Scholar 

  • Krinsky NI, Denekem SM (1982) Interaction of oxygen and oxyradicals with carotenoids. J Natl Cancer Inst 69:205–210

    CAS  PubMed  Google Scholar 

  • Kulkarni AP, Byczkowski JZ (1994) Introduction to biochemical toxicology, 2nd edn. Appleton and Lange, Connecticut, pp 103–105

  • Leinonen JS, Ahonen JP, Lonnrot K, Jechonen M, Dastidar P, Molnar J, Alho H (2000) Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke. Stroke 31:33–39

    CAS  PubMed  Google Scholar 

  • Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    CAS  PubMed  Google Scholar 

  • Luxia AS, Monica S, Ornella C, Plizzala B, Laura R, Livia B, Anio M, Ennio P (1996) Effect of b-carotene on cell cycle progression of human fibroblasts. Mutagen 17:2395–2401

    Google Scholar 

  • Mathew WB, Sanakranarayana R, Nair P, Varghese C, Somanathan T, Amma P, Amma N, Nair M (1995) Evaluation of chemoprevention of oral cancer with Spirulina fusiformis. Nutr Cancer 24:197–202

    Article  CAS  PubMed  Google Scholar 

  • Miranda MS, Cintra RG, Barros SM, Macini-Fitho J (1998) Antioxidant activity of the microalgae Spirulina maxima. Braz J Med Biol Res 31:1075–1079

    Article  CAS  PubMed  Google Scholar 

  • Misra HP, Fridovich J (1972) The role of Superoxide anion in the auto oxidation of epinephrine and simple assay for superoxide dismutase. J Biol chem 247:3170–3175

    CAS  PubMed  Google Scholar 

  • Mitchell GV, Grundel E, Jenkins M, Blakely SR (1990) Effects of graded dietary levels of Spirulina maxima on vitamins A and E in male rats. J Nutr 120:1235–1240

    CAS  PubMed  Google Scholar 

  • Moreno JJ, Pryor WA (1992) Inactivation of alpha 1-proteinase inhibitor by peroxynitrite. Chem Res Toxicol 5:425–431

    Article  CAS  PubMed  Google Scholar 

  • Morimoto T, Globus MY, Busto R, Martinez E, Ginsberg MD (1996) Simultaneous measurement of salicylate hydroxylation and glutamate release in the penumbral cortex following transient middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab 16:92–99

    Article  CAS  PubMed  Google Scholar 

  • Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349:1269–1276

    Article  CAS  PubMed  Google Scholar 

  • Nakashima M, Niwa M, Iwai T, Uematsu T (1999) Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat. Free Radic Biol Med 26:722–729

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animals and tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Parikh V, Mohammad Khan M, Mahadik SP (2003) Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J Psychiatr Res 37:43–51

    Google Scholar 

  • Park SJ, Nam KW, Lee HJ, Cho EY, Koo U, Mar W (2009) Neuroprotective effects of an alkaloid free ethyl acetate extract from the root of Sophora flavescens Ait. Against focal cerebral ischemia in rats. Phytomedicine 16(11):1042–1051

    Google Scholar 

  • Polidori MC, Cherubini A, Stahl W, Senin U, Sies H (2002) Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome. Free Radic Res 36:265–268

    Article  CAS  PubMed  Google Scholar 

  • Premkumar K, Pachiappan A, Abraham SK, Santhiya ST, Gopinath PM, Ramesh A (2001) Effect of Spirulina fusiformis on cyclophosphamide and mitomycin-C induced genotoxicity and oxidative stress in mice. Fitoterapia 72:906–911

    Article  CAS  PubMed  Google Scholar 

  • Prescott GW (1978) How to know the fresh water algae? 3rd edn. Wn.C., Brown Company Publishers, Iowa, p 182

    Google Scholar 

  • Re G, Azzimondi G, Lanzarini C, Bassein L, Vaona I (1997) Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism. Eur J Emerg Med 4:5–9

    CAS  PubMed  Google Scholar 

  • Reddy CM, Bhat VB, Kiranmai G, Reddy MN, Reddanna P, Madyastha KM (2000) Selective inhibition of cyclooxygense-2 by C-phycocyanin, a biliprotein from Spirulina platensis. Biochem Biophys Res Commun 277:599–603

    Article  CAS  PubMed  Google Scholar 

  • Romay C, Gonzalez R (2000) Phycocyanin is an antioxidant protector of human erythrocytes against lysis by peroxyl radicals. J Pharmacol 52:367–368

    Article  CAS  Google Scholar 

  • Romay C, Armesto J, Remirez D, Gonzalez R, Ledon N, Garcia I (1998) Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae. Inflamm Res 47:36–41

    Article  CAS  PubMed  Google Scholar 

  • Saybasili H, Yuksel M, Haklar G, Yalcin AS (2001) Effect of mitochondrial electron transport chain inhibitors on superoxide radical generation in rat hippocampal and striatal slices. Antioxid Redox signal 3:1099–1104

    Article  CAS  PubMed  Google Scholar 

  • Saybasili H, Yuksel M, Haklar G, Yalcin AS (2002) Depolarization induced superoxide formation in rat hippocampal slices. Neurochem Res 27:473–476

    Article  CAS  PubMed  Google Scholar 

  • Shah ZA, Gilani RA, Sharma P, Vohora SB (2005) Cerebroprotective effect of Korean ginseng tea against global and focal models of ischemia in rats. J Ethnopharmacol 101:299–307

    Article  CAS  PubMed  Google Scholar 

  • Sharpe PC, Mulholland C, Trinick T (1994) Ascorbate and malondialdehyde in stroke patients. Ir J Med Sci 163:488–491

    Article  CAS  PubMed  Google Scholar 

  • Sheshadri CV, Umesh BV, Manoharan R (1991) β-Carotene studies in spirulina. Bio resource Technol 38:111–113

    Google Scholar 

  • Shimamatsu S (1989) Cited from RECON. Recon Limited, A rainbow of colorful pigments, Bangalore, pp 13–14

    Google Scholar 

  • Shivakumar BR, Kolluri SV, Ravindranath V (1995) Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. J Pharmacol Exp Ther 274:1167–1173

    CAS  PubMed  Google Scholar 

  • Shukla PK, Khanna VK, Ali MM, Mourya R, Khan MY, Srimal RC (2006) Neuroprotective effect of Acorus Calamus against middle cerebral artery occlusion induced ischemia in rats. Hum Exp Toxicol 25:187–194

    Article  PubMed  Google Scholar 

  • Soska V, Olsovsky J, Zechmeister A, Lojek A, Bouda J, Garcia Escamilla RM (1997) Free oxygen radicals and lipoperoxides in type 2 diabetic patients. Revisions Mexicana Pathologists Clinicians 44:62–66

    Google Scholar 

  • Spranger M, Krempien S, Schwab S, Donneberg S, Hacke W (1997) Superoxide dismutase activity in serum of patients with acute cerebral ischemic injury: correlation with clinical course and infarct size. Stroke 28:2425–2428

    CAS  PubMed  Google Scholar 

  • Takai Y, Hossayamada Y, Kato T (1991) Effect of water soluble and water insoluble fractions of Spirulina over serum lipids and glucose resistance of rats. J Jpn Soc Nutr Food Sci 44:273–277

    Google Scholar 

  • Thaakur SR, Jyothi B (2007) Effect of Spirulina maxima on the haloperidol induced tardive dyskinesia and oxidative stress in rats. J Neural Transm 114:1217–1225

    Article  CAS  PubMed  Google Scholar 

  • Thaakur SR, Pushpa B (2008) Effect of Spirulina on Phynotoin induced selected behavioural abnormalities and regional brain lipid peroxidation in rats. Int J Neuro Degeneration Regeneration 4:263–272

    Google Scholar 

  • Thiyagarajan M, Sharma SS (2004) Neuroprotective effect of Curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 74:969–985

    Article  CAS  PubMed  Google Scholar 

  • Upasani CD, Khera A, Balaraman R (2001) Effect of lead with vitamin E, C or Spirulina on malondialdehyde, conjugated dienes and hydroperoxides in rats. Indian J Exp Biol 39:70–74

    CAS  PubMed  Google Scholar 

  • Viglino P, Scara M, Rotilio G, Rigo A (1988) A kinectic study of the reactions between H2O2 and Cu, Zn superoxide dismutase, evidence for an electrostatic control of the reaction rate. Biochem Biophys Acta 952:77–82

    CAS  PubMed  Google Scholar 

  • Wang Y, Chang CF, Chou J, Chen HL, Deng X, Harvey BK, Cadet JL, Bickford PC (2005) Dietary supplementation with blue berries, spinach or spirulina reduces ischemic brain damage. Exp Neurol 193:75–84

    Article  CAS  PubMed  Google Scholar 

  • Yang GY, Pang L, Ge HL, Tan M, Ye W, Liu XH, Huang FP, Wu DC, Che XM, Song Y, Wen R, Sun Y (2001) Attenuation of ischemia-induced mouse brain injury by SAG, a redox-inducible antioxidant protein. J Cereb Blood Flow Metab 21:722–733

    Article  CAS  PubMed  Google Scholar 

  • Yanpallewar SU, Rai S, Kumar M, Acharya SB (2004) Evaluation of antioxidant and neuroprotective effect of Ocimum sanctum on transient cerebral ischemia and long term cerebral hypoperfusion. Pharmacol Biochem Behav 79:155–164

    Article  CAS  PubMed  Google Scholar 

  • Yao JK, Reddy R, Elhinny LG, Vankammen DP (1998) Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. J Psychiatr Res 32:385–391

    Article  CAS  PubMed  Google Scholar 

  • Zang C, Yang J (2006) Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion induced focal cerebral ischemia in rats. Pharmacol Res 55:303–309

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pharmacology, Institute of Pharmaceutical Technology, Sri Padmavathi Mahila Visvavidyalayam, Tirupathi, 517502, Chittoor dist., Andhra Pradesh, India

    Santhrani Thaakur & Ravi Sravanthi

Authors
  1. Santhrani Thaakur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ravi Sravanthi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Santhrani Thaakur.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thaakur, S., Sravanthi, R. Neuroprotective effect of Spirulina in cerebral ischemia–reperfusion injury in rats. J Neural Transm 117, 1083–1091 (2010). https://doi.org/10.1007/s00702-010-0440-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-010-0440-5

Keywords

Search

Navigation