Skip to main content
Log in

Neuroprotective Effect of DAHK Peptide in an Occlusive Model of Permanent Focal Ischemia in Rats

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

This study examined the neuroprotective ability of tetrapeptide l-Asp-Ala-His-Lys (DAHK) in permanent middle cerebral artery occlusion in rats. One DAHK dose (16 mg/kg) or saline solution were i.v. administered 30 min after occlusion and neurological deficit was evaluated at 2, 24, 48, 72 and 96 h using Longa scoring scale. The striatum infarction area was evaluated until 96 h after occlusion in both groups after staining with hematoxylin–eosin. DAHK-treated group showed a significant (P < 0.05) protection of 70% of neurological deficit at 96 h after occlusion, in comparison with the control-group that showed permanent neurological deficit. The DAHK-treated group showed a significant (P < 0.05) reduction of 52% infarction area in the striatum, as compared to control values. Results presented here support the possible therapeutic application of DAHK as a neuroprotective agent in human patients with stroke, as the peptide is part of human serum albumin, already being tested in clinical trials.

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

Similar content being viewed by others

References

  1. Dodel RC, Haacke C, Zamzow K, Paweilik S, Spottke A, Rethfeldt M, Siebert U, Oertel WH, Schoffsky O, Back T (2004) Resource utilization and cost of stroke unit care in Germany. Value Health 7:144–152

    Article  PubMed  Google Scholar 

  2. American Heart Association (2005) Heart disease and stroke statistics. American Heart Association, Dallas

  3. Spieler JF, Lanoe JL, Amarenco P (2004) Costs of stroke care according to handicap levels and stroke subtypes. Cerebrovasc Dis 17:134–142

    Article  PubMed  Google Scholar 

  4. Dirnagl U, Iadecola C, Moskowitz M (1999) Pathobiology of ischemic stroke: an integrated view. Trends Neurosci 22:391–397

    Article  CAS  PubMed  Google Scholar 

  5. Ginsberg MD (2003) Adventures in the pathophysiology of brain ischemic: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture. Stroke 34:214–223

    Article  PubMed  Google Scholar 

  6. Hacke W, Ringleb P, Stingele R (1999) How did the results of ECASS II influence clinical practice of treatment of acute stroke. Rev Neurol 29:638–641

    CAS  PubMed  Google Scholar 

  7. Alonso de Leciñana M, Diez-Tejedor E, Gutierrez M, Guerrero S, Carceller F, Roda JM (2005) New goals in ischemic stroke therapy: the experimental approach-harmonizing science with practice. Cerebrovasc Dis 20:59–168

    Google Scholar 

  8. Ginsberg MD (2008) Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 55:363–389

    Article  CAS  PubMed  Google Scholar 

  9. Belayev L, Liu Y, Zhao W, Busto R, Ginsberg MD (2001) Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke 32:553–560

    CAS  PubMed  Google Scholar 

  10. Gum ET, Swanson RA, Alano C, Liu J, Hong S, Weinstein PR, Panter SS (2004) Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidant-induced neuronal death. Stroke 35:590–595

    Article  CAS  PubMed  Google Scholar 

  11. Merrifield B (1986) Solid phase synthesis. Science 232:341–347

    Article  CAS  PubMed  Google Scholar 

  12. Valdez-Cruz NA, Batista CV, Possani LD (1004) Phaiodactylipin, a glycosylated heterodimeric phospholipase A from the venom of the scorpion Anuroctonus phaiodactylus. Eur J Biochem 271:1453–1464

    Article  Google Scholar 

  13. Batista CV, Del Pozo L, Zamudio FZ, Contreras S, Becerril B, Wanke E, Possani LD (2004) Proteomics of the venom from the Amazonian scorpion Tityus cambridgei and the role of prolines on mass spectrometry analysis of toxins. J Chromatogr B Analyt Technol Biomed Life Sci 803:55–66

    Article  CAS  PubMed  Google Scholar 

  14. Possani LD, Martin BM, Svendsen I, Rode G, Erickson BW (1985) Scorpion toxins from Centruroides noxius and Tityus serrulatus: primary structures and sequence comparison by metric analysis. Biochem J 229:739–750

    CAS  PubMed  Google Scholar 

  15. 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 

  16. Belayev L, Pinard E, Nallet H, Seylaz J, Liu Y, Riyamongkol P, Zhao W, Busto R, Ginsberg MD (2002) Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses. Stroke 33:1077–1084

    Article  PubMed  Google Scholar 

  17. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego, p 340

    Google Scholar 

  18. Niyaz M, Numakawa T, Matsuki Y, Kumamaru E, Adachi N, Kitazawa H, Kunugi H, Kudo M (2007) MCI-186 prevents brain tissue from neuronal damage in cerebral infarction through the activation of intracellular signaling. J Neurosci Res 85:2933–2942

    Article  CAS  PubMed  Google Scholar 

  19. Matsui T, Sinyama H, Asano T (1993) Beneficial effect of prolonged administration of albumin on ischemic cerebral edema and infarction after occlusion of middle cerebral artery in rats. Neurosurgery 33:293–300

    Article  CAS  PubMed  Google Scholar 

  20. Belayev L, Zhao W, Pattany PM, Weaver RG, Huh PW, Lin B, Busto R, Ginsberg MD (1998) Diffusion-weighted magnetic resonance imaging confirms marked neuroprotective efficacy of albumin therapy in focal cerebral ischemia. Stroke 29:2587–2599

    CAS  PubMed  Google Scholar 

  21. Bar-Or D, Rael LT, Lau EP, Rao NKR, Thomas GW, Winkler JV, Yukl RL, Kingston RG, Curtis CG (2001) An analog of the human serum albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species. Biochem Biophys Res Commun 284:856–862

    Article  CAS  PubMed  Google Scholar 

  22. Bar-Or D, McDonald MC, Thiemermann C (2006) Reduction of infarct size in a rat model of regional myocardial ischemia and reperfusion by the synthetic peptide DAHK. Crit Care Med 34:1955–1959

    Article  CAS  PubMed  Google Scholar 

  23. Predki PF, Harford C, Brar P, Sarkar B (1992) Further characterization of the N-terminus copper(II)- and nickel(II)- binding motif of proteins. Studies of metal binding to chicken serum albumin and the native sequence peptide. Biochem J 287:211–215

    CAS  PubMed  Google Scholar 

  24. Reinhart WH, Nagy C (1995) Albumin affects erythrocyte aggregation and sedimentation. Eur J Clin Invest 25:523–527

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We want to thank the Fundación Miguel Alemán A.C. for the support of this study, and the support through a PROMEP/SEP fellowship granted to J. Carbajal-Sotelo. The authors acknowledged the support received from the laboratory of Dr. Lourival Possani from the Biotechnology Institute of UNAM.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Monroy-Noyola.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Díaz-Ruíz, A., Ríos, C., Carvajal-Sotelo, J. et al. Neuroprotective Effect of DAHK Peptide in an Occlusive Model of Permanent Focal Ischemia in Rats. Neurochem Res 35, 343–347 (2010). https://doi.org/10.1007/s11064-009-0060-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-009-0060-3

Keywords

Navigation