Skip to main content

Advertisement

SpringerLink
Log in

Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice

  • Published:
AGE Aims and scope Submit manuscript

Abstract

The cardiovascular complications reported to be associated with cyclooxygenase inhibitor use have shifted our focus toward prostaglandins and their respective receptors. Prostaglandin D2 and its DP1 receptor have been implicated in various normal and pathologic conditions, but their role in stroke is still poorly defined. Here, we tested whether DP1 deletion aggravates N-methyl-d-aspartic acid (NMDA)-induced acute toxicity and whether DP1 pharmacologic activation protects mice from acute excitotoxicity and transient cerebral ischemia. Moreover, since the elderly are more vulnerable to stroke-related damage than are younger patients, we tested the susceptibility of aged DP1 knockout (DP1−/−) mice to brain damage. We found that intrastriatal injection of 15 nmol NMDA caused significantly larger lesion volumes (27.2 ± 6.4%) in young adult DP1−/− mice than in their wild-type counterparts. Additionally, intracerebroventricular pretreatment of wild-type mice with 10, 25, and 50 nmol of the DP1-selective agonist BW245C significantly attenuated the NMDA-induced lesion size by 19.5 ± 5.0%, 39.6 ± 7.7%, and 28.9 ± 7.0%, respectively. The lowest tested dose of BW245C also was able to reduce middle cerebral artery occlusion-induced brain infarction size significantly (21.0 ± 5.7%). Interestingly, the aggravated NMDA-induced brain damage was persistent in older DP1−/− mice as well. We conclude that the DP1 receptor plays an important role in attenuating brain damage and that selective targeting of this receptor could be considered as an adjunct therapeutic tool to minimize stroke damage.

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

Similar content being viewed by others

References

  • Abdel-Halim MS, Hamberg M, Sjoquist B, Anggard E (1977) Identification of prostaglandin D2 as a major prostaglandin in homogenates of rat brain. Prostaglandins 14:633–643. doi:10.1016/0090-6980(77)90190-3

    Article  CAS  PubMed  Google Scholar 

  • Abramovitz M, Adam M, Boie Y, Carriere M, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM et al (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 1483:285–293. doi:10.1016/S1388-1981(99)00164-X

    CAS  PubMed  Google Scholar 

  • Ahmad AS, Saleem S, Ahmad M, Doré S (2006a) Prostaglandin EP1 receptor contributes to excitotoxicity and focal ischemic brain damage. Toxicol Sci 89:265–270. doi:10.1093/toxsci/kfj022

    Article  CAS  PubMed  Google Scholar 

  • Ahmad AS, Zhuang H, Echeverria V, Doré S (2006b) Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. J Neurotrauma 23:1895–1903. doi:10.1089/neu.2006.23.1895

    Article  PubMed  Google Scholar 

  • Ahmad M, Saleem S, Zhuang H, Ahmad AS, Echeverria V, Sapirstein A, Doré S (2006c) 1-HydroxyPGE1 reduces infarction volume in mouse transient cerebral ischemia. Eur J Neurosci 23:35–42. doi:10.1111/j.1460-9568.2005.04540.x

    Article  PubMed  Google Scholar 

  • Alving K, Matran R, Lundberg JM (1991) The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig. Acta Physiol Scand 143:93–103. doi:10.1111/j.1748-1716.1991.tb09204.x

    Article  CAS  PubMed  Google Scholar 

  • Angeli V, Staumont D, Charbonnier AS, Hammad H, Gosset P, Pichavant M, Lambrecht BN, Capron M, Dombrowicz D, Trottein F (2004) Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses. J Immunol 172:3822–3829

    CAS  PubMed  Google Scholar 

  • Banay-Schwartz M, Lajtha A, Palkovits M (1989) Changes with aging in the levels of amino acids in rat CNS structural elements. I. Glutamate and related amino acids. Neurochem Res 14:555–562

    Article  CAS  PubMed  Google Scholar 

  • Bohm E, Sturm GJ, Weiglhofer I, Sandig H, Shichijo M, McNamee A, Pease JE, Kollroser M, Peskar BA, Heinemann A (2004) 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. J Biol Chem 279:7663–7670. doi:10.1074/jbc.M310270200

    Article  PubMed  Google Scholar 

  • Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102. doi:10.1056/NEJMc066260

    Article  CAS  PubMed  Google Scholar 

  • Brus R, Herman ZS, Szklinik R (1980) Central effects of prostaglandin D2. Pol J Pharmacol Pharm 32:681–684

    CAS  PubMed  Google Scholar 

  • Campbell IG, Feinberg I (1996) Noncompetitive NMDA channel blockade during waking intensely stimulates NREM delta. J Pharmacol Exp Ther 276:737–742

    CAS  PubMed  Google Scholar 

  • Casteleijn E, Kuiper J, Van Rooij HC, Kamps JA, Koster JF, Van Berkel TJ (1988) Prostaglandin D2 mediates the stimulation of glycogenolysis in the liver by phorbol ester. Biochem J 250:77–80

    CAS  PubMed  Google Scholar 

  • Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14. doi:10.1097/00004647-200101000-00002

    Article  CAS  PubMed  Google Scholar 

  • Cheng K, Wu TJ, Wu KK, Sturino C, Metters K, Gottesdiener K, Wright SD, Wang Z, O'Neill G, Lai E et al (2006) Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc Natl Acad Sci U S A 103:6682–6687. doi:10.1073/pnas.0601574103

    Article  CAS  PubMed  Google Scholar 

  • Cohen SA, Muller WE (1992) Age-related alterations of NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidylserine treatment. Brain Res 584:174–180

    Article  CAS  PubMed  Google Scholar 

  • Darius H, Michael-Hepp J, Thierauch KH, Fisch A (1994) Inhibition of human platelets and polymorphonuclear neutrophils by the potent and metabolically stable prostaglandin D2 analog ZK 118.182. Eur J Pharmacol 258:207–213

    Article  CAS  PubMed  Google Scholar 

  • Dickstein DL, Kabaso D, Rocher AB, Luebke JI, Wearne SL, Hof PR (2007) Changes in the structural complexity of the aged brain. Aging Cell 6:275–284

    Article  CAS  PubMed  Google Scholar 

  • Echeverria V, Clerman A, Doré S (2005) Stimulation of PGE2 receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following β-amyloid exposure. Eur J Neurosci 22:2199–2206. doi:10.1111/j.1460-9568.2005.04427.x

    Article  PubMed  Google Scholar 

  • Eguchi N, Minami T, Shirafuji N, Kanaoka Y, Tanaka T, Nagata A, Yoshida N, Urade Y, Ito S, Hayaishi O (1999) Lack of tactile pain (allodynia) in lipocalin-type prostaglandin D synthase-deficient mice. Proc Natl Acad Sci U S A 96:726–730

    Article  CAS  PubMed  Google Scholar 

  • Endres M, Engelhardt B, Koistinaho J, Lindvall O, Meairs S, Mohr JP, Planas A, Rothwell N, Schwaninger M, Schwab ME et al (2008) Improving outcome after stroke: overcoming the translational roadblock. Cerebrovasc Dis 25:268–278. doi:10.1159/000118039

    Article  PubMed  Google Scholar 

  • Gelir E, Arslan SO, Sayan H, Pinar L (2005) Effect of rapid-eye-movement sleep deprivation on rat hypothalamic prostaglandins. Prostaglandins Leukot Essent Fatty Acids 73:391–396. doi:10.1016/j.plefa.2005.05.021

    Article  CAS  PubMed  Google Scholar 

  • Giles H, Leff P, Bolofo ML, Kelly MG, Robertson AD (1989) The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist. Br J Pharmacol 96:291–300

    CAS  PubMed  Google Scholar 

  • Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA (2005) Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 365:475–481. doi:10.1016/S0140-6736(05)17864-7

    CAS  PubMed  Google Scholar 

  • Hamid-Bloomfield S, Whittle BJ (1989) Antagonism of PGD2 vasodepressor responses in the rat in vivo by the novel, selective antagonist, BW A868C. Br J Pharmacol 96:307–312

    CAS  PubMed  Google Scholar 

  • Hammad H, de Heer HJ, Soullie T, Hoogsteden HC, Trottein F, Lambrecht BN (2003) Prostaglandin D2 inhibits airway dendritic cell migration and function in steady state conditions by selective activation of the D prostanoid receptor 1. J Immunol 171:3936–3940

    CAS  PubMed  Google Scholar 

  • Hartikka J, Staufenbiel M, Lubbert H (1992) Cyclic AMP, but not basic FGF, increases the in vitro survival of mesencephalic dopaminergic neurons and protects them from MPP(+)-induced degeneration. J Neurosci Res 32:190–201

    Article  CAS  PubMed  Google Scholar 

  • Hata AN, Breyer RM (2004) Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther 103:147–166. doi:10.1016/j.pharmthera.2004.06.003

    Article  CAS  PubMed  Google Scholar 

  • Hayaishi O (2002) Molecular genetic studies on sleep–wake regulation, with special emphasis on the prostaglandin D2 system. J Appl Physiol 92:863–868. doi:10.1152/japplphysiol.00766.2001

    CAS  PubMed  Google Scholar 

  • Hayaishi O, Urade Y (2002) Prostaglandin D2 in sleep–wake regulation: recent progress and perspectives. Neuroscientist 8:12–15. doi:10.1177/107385840200800105

    Article  CAS  PubMed  Google Scholar 

  • Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S et al (2001) Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 193:255–261

    Article  CAS  PubMed  Google Scholar 

  • Ientile R, De Sarro A, Rotiroti D, De Sarro GB, Nistico G (1983) Stimulation of rat caudate nucleus adenylate cyclase activity by BW 245 C, a prostaglandin analogue with prostacyclin-like activity. J Pharm Pharmacol 35:62–64

    CAS  PubMed  Google Scholar 

  • Ito S, Narumiya S, Hayaishi O (1989) Prostaglandin D2: a biochemical perspective. Prostaglandins Leukot Essent Fatty Acids 37:219–234

    Article  CAS  PubMed  Google Scholar 

  • Kandasamy SB, Hunt WA (1990) Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats. Radiat Res 121:84–90

    Article  CAS  PubMed  Google Scholar 

  • Kiriyama M, Ushikubi F, Kobayashi T, Hirata M, Sugimoto Y, Narumiya S (1997) Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol 122:217–224. doi:10.1038/sj.bjp. 0701367

    Article  CAS  PubMed  Google Scholar 

  • Koch KA, Wessale JL, Moreland R, Reinhart GA, Cox BF (2005) Effects of BW245C, a prostaglandin DP receptor agonist, on systemic and regional haemodynamics in the anaesthetized rat. Clin Exp Pharmacol Physiol 32:931–935. doi:10.1111/j.1440-1681.2005.04287.x

    Article  CAS  PubMed  Google Scholar 

  • Liang X, Wu L, Hand T, Andreasson K (2005) Prostaglandin D2 mediates neuronal protection via the DP1 receptor. J Neurochem 92:477–486. doi:10.1111/j.1471-4159.2004.02870.x

    Article  CAS  PubMed  Google Scholar 

  • Magnusson KR, Cotman CW (1993) Age-related changes in excitatory amino acid receptors in two mouse strains. Neurobiol Aging 14:197–206

    Article  CAS  PubMed  Google Scholar 

  • Matsugi T, Kageyama M, Nishimura K, Giles H, Shirasawa E (1995) Selective prostaglandin D2 receptor stimulation elicits ocular hypotensive effects in rabbits and cats. Eur J Pharmacol 275:245–250. doi:10.1016/0014-2999(94)00788-9

    Article  CAS  PubMed  Google Scholar 

  • Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y et al (2000) Prostaglandin D2 as a mediator of allergic asthma. Science 287:2013–2017. doi:10.1126/science.287.5460.2013

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Guthrie PB, Kater SB (1988) Intracellular messengers in the generation and degeneration of hippocampal neuroarchitecture. J Neurosci Res 21:447–464

    Article  CAS  PubMed  Google Scholar 

  • McCullough L, Wu L, Haughey N, Liang X, Hand T, Wang Q, Breyer RM, Andreasson K (2004) Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia. J Neurosci 24:257–268. doi:10.1523/JNEUROSCI.4485-03.2004

    Article  CAS  PubMed  Google Scholar 

  • Mizoguchi A, Eguchi N, Kimura K, Kiyohara Y, Qu WM, Huang ZL, Mochizuki T, Lazarus M, Kobayashi T, Kaneko T et al (2001) Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep. Proc Natl Acad Sci U S A 98:11674–11679. doi:10.1073/pnas.201398898

    Article  CAS  PubMed  Google Scholar 

  • Moore LE, Traystman RJ (1994) Role of oxygen free radicals and lipid peroxidation in cerebral reperfusion injury. In: Bosnjak ZJ, August JT (eds) Adv Pharmacol. Academic, San Diego, pp 565–576

    Google Scholar 

  • Narumiya S, FitzGerald GA (2001) Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest 108:25–30

    CAS  PubMed  Google Scholar 

  • Narumiya S, Toda N (1985) Different responsiveness of prostaglandin D2-sensitive systems to prostaglandin D2 and its analogues. Br J Pharmacol 85:367–375

    PubMed  Google Scholar 

  • Narumiya S, Ogorochi T, Nakao K, Hayaishi O (1982) Prostaglandin D2 in rat brain, spinal cord and pituitary: basal level and regional distribution. Life Sci 31:2093–2103

    Article  CAS  PubMed  Google Scholar 

  • Narumiya S, Sugimoto Y, Ushikubi F (1999) Prostanoid receptors: structures, properties, and functions. Physiol Rev 79:1193–1226

    CAS  PubMed  Google Scholar 

  • Obal F Jr, Krueger JM (2003) Biochemical regulation of non-rapid-eye-movement sleep. Front Biosci 8:d520–d550

    Article  CAS  PubMed  Google Scholar 

  • Ogorochi T, Narumiya S, Mizuno N, Yamashita K, Miyazaki H, Hayaishi O (1984) Regional distribution of prostaglandins D2, E2, and F2 alpha and related enzymes in postmortem human brain. J Neurochem 43:71–82

    Article  CAS  PubMed  Google Scholar 

  • Peterson C, Cotman CW (1989) Strain-dependent decrease in glutamate binding to the N-methyl-d-aspartic acid receptor during aging. Neurosci Lett 104:309–313

    Article  CAS  PubMed  Google Scholar 

  • Rangachari P, Betti P, Prior E, Ln R (1995) Effects of a selective DP receptor agonist (BW 245C) and antagonist (BW A868C) on the canine colonic epithelium: an argument for a different DP receptor? J Pharmacol Exp Ther 275:611–617

    CAS  PubMed  Google Scholar 

  • Rosamond W, Flegal K, Furie K, Go A, Greenlund K, Haase N, Hailpern SM, Ho M, Howard V, Kissela B et al (2008) Heart disease and stroke statistics–2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 117:e25–e146. doi:10.1161/CIRCULATIONAHA.107.187998

    Article  PubMed  Google Scholar 

  • Saleem S, Zhuang H, de Brum-Fernandes AJ, Maruyama T, Narumiya S, Doré S (2007) PGD2 DP1 receptor protects brain from ischemia–reperfusion injury. Eur J Neurosci 26:73–78. doi:10.1111/j.1460-9568.2007.05627.x

    Article  PubMed  Google Scholar 

  • Saleem S, Shah ZA, Urade Y, Doré S (2009) Lipocalin-prostaglandin D synthase is a critical beneficial factor in transient and permanent focal cerebral ischemia. Neuroscience 160:248–254. doi:10.1016/j.neuroscience.2009.02.039

    Article  CAS  PubMed  Google Scholar 

  • Sandig H, Andrew D, Barnes AA, Sabroe I, Pease J (2006) 9α, 11β-PGF2 and its stereoisomer PGF2α are novel agonists of the chemoattractant receptor, CRTH2. FEBS Lett 580:373–379. doi:10.1016/j.febslet.2005.11.052

    Article  CAS  PubMed  Google Scholar 

  • Saransaari P, Oja SS (1995) Age-related changes in the uptake and release of glutamate and aspartate in the mouse brain. Mech Ageing Dev 81:61–71

    Article  CAS  PubMed  Google Scholar 

  • Sawyer N, Cauchon E, Chateauneuf A, Cruz RPG, Nicholson DW, Metters KM, O'Neill GP, Gervais FG (2002) Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Br J Pharmacol 137:1163–1172. doi:10.1038/sj.bjp. 0704973

    Article  CAS  PubMed  Google Scholar 

  • Segovia G, Porras A, Del Arco A, Mora F (2001) Glutamatergic neurotransmission in aging: a critical perspective. Mech Ageing Dev 122:1–29

    Article  CAS  PubMed  Google Scholar 

  • Shirahase H, Kanda M, Nakamura S, Tarumi T, Uehara Y, Ichikawa A (2000) Inhibitory effects of PGD2, PGJ2 and 15-deoxy-Δ12, 14-PGJ2 on iNOS induction in rat mesenteric artery. Life Sci 66:2173–2182. doi:10.1016/S0024-3205(00)00544-0

    Article  CAS  PubMed  Google Scholar 

  • Siren AL (1982) Central cardiovascular and thermal effects of prostaglandin D2 in rats. Prostaglandins Leukot Med 8:349–359

    Article  CAS  PubMed  Google Scholar 

  • Sklair-Tavron L, Segal M (1993) Neurotrophic effects of cAMP generating systems on central noradrenergic neurons. Brain Res 614:257–269. doi:10.1016/0006-8993(93)91043-R

    Article  CAS  PubMed  Google Scholar 

  • Spik I, Brenuchon C, Angeli V, Staumont D, Fleury S, Capron M, Trottein F, Dombrowicz D (2005) Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. J Immunol 174:3703–3708

    CAS  PubMed  Google Scholar 

  • Sturzebecher S, Nieuweboer B, Matthes S, Schillinger E (1989) Effects of PGD2, PGE1, and PGI2-analogues on PGDF-release and aggregation of human gel filtered platelets. Prog Clin Biol Res 301:365–369

    CAS  PubMed  Google Scholar 

  • Toyomoto M, Ohta M, Okumura K, Yano H, Matsumoto K, Inoue S, Hayashi K, Ikeda K (2004) Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures. FEBS Lett 562:211–215. doi:10.1016/S0014-5793(04)00246-7

    Article  CAS  PubMed  Google Scholar 

  • Urade Y, Hayaishi O (1999) Prostaglandin D2 and sleep regulation. Biochim Biophys Acta 1436:606–615. doi:10.1016/S0005-2760(98)00163-5

    CAS  PubMed  Google Scholar 

  • Walch L, Labat C, Gascard JP, de Montpreville V, Brink C, Norel X (1999) Prostanoid receptors involved in the relaxation of human pulmonary vessels. Br J Pharmacol 126:859–866. doi:10.1038/sj.bjp. 0702393

    Article  CAS  PubMed  Google Scholar 

  • Wenk GL, Walker LC, Price DL, Cork LC (1991) Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys. Neurobiol Aging 12:93–98

    Article  CAS  PubMed  Google Scholar 

  • Whittle BJ, Moncada S, Mullane K, Vane JR (1983) Platelet and cardiovascular activity of the hydantoin BW245C, a potent prostaglandin analogue. Prostaglandins 25:205–223

    Article  CAS  PubMed  Google Scholar 

  • Wright DH, Metters KM, Abramovitz M, Ford-Hutchinson AW (1998) Characterization of the recombinant human prostanoid DP receptor and identification of L-644, 698, a novel selective DP agonist. Br J Pharmacol 123:1317–1324. doi:10.1038/sj.bjp. 0701708

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from the National Institutes of Health NS046400 and AG022971 (SD) and the American Heart Association 0830172N (ASA). We thank Claire Levine for assistance in the preparation of the manuscript and all members of the Doré lab team for assistance in this project.

Conflict of interest

None of the authors have any conflict of interest associated with this work.

Author information

Authors and Affiliations

  1. Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave., Ross 364, Baltimore, MD, 21205, USA

    Abdullah Shafique Ahmad, Muzamil Ahmad & Sylvain Doré

  2. Pharmacological Research Laboratories, Ono Pharmaceutical Co. Ltd., Mishima-gun, Osaka, Japan

    Takayuki Maruyama

  3. Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan

    Shuh Narumiya

  4. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Sylvain Doré

Authors
  1. Abdullah Shafique Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muzamil Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takayuki Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuh Narumiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sylvain Doré
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sylvain Doré.

Additional information

A. S. Ahmad and M. Ahmad contributed equally to this work.

About this article

Cite this article

Ahmad, A.S., Ahmad, M., Maruyama, T. et al. Prostaglandin D2 DP1 receptor is beneficial in ischemic stroke and in acute exicitotoxicity in young and old mice. AGE 32, 271–282 (2010). https://doi.org/10.1007/s11357-010-9135-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-010-9135-y

Keywords

Search

Navigation