Faculty

Pioneering Rehabilitation

Saravanan S. Karuppagounder, Ph.D.

Director, Sperling Center for Hemorrhagic Stroke Recovery

About Saravanan Karuppagounder

Instructor
Brain and Mind Research Institute
Weill Cornell Medicine

Phone:

(914) 597-2696

Research Focus

My research interests focus on the use of small molecule inhibitors of hypoxia inducible factor prolyl hydroxylases (HIF PHDs) as novel therapeutics for intracerebral hemorrhage. We have developed an in vitro model to mimic hemorrhagic stroke using hemin, which induces cell death in various neuronal cell types that is rescued by PHD inhibitors. We also utilize an in vivo rat or mice models for hemorrhagic stroke using autologous blood infusion or hemin. We are testing the efficacy of PHD inhibitors in these preclinical animal models using end points including brain edema volume, neuronal survival, and behavioral outcomes. Our findings suggest that PHD inhibitors are promising candidates for preventing cell death in hemorrhagic stroke.

Publications

Citations via PubMed

Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, Stringer T, Ulja D, Karuppagounder SS, Holson EB, Ratan RR, Ninan I, Chao MV (2016). Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate Elife 2016 Jun;5 PMID: 27253067

Neitemeier S, Dolga AM, Honrath B, Karuppagounder SS, Alim I, Ratan RR, Culmsee C (2016). Inhibition of HIF-prolyl-4-hydroxylases prevents mitochondrial impairment and cell death in a model of neuronal oxytosis Cell Death Dis 2016;7:e2214 PMID: 27148687

Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, Thinnes CC, Yeh TL, Demetriades M, Neitemeier S, Cruz D, Gazaryan I, Killilea DW, Morgenstern L, Xi G, Keep RF, Schallert T, Tappero RV, Zhong J, Cho S, Maxfield FR, Holman TR, Culmsee C, Fong GH, Su Y, Ming GL, Song H, Cave JW, Schofield CJ, Colbourne F, Coppola G, Ratan RR (2016). Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models Sci Transl Med 2016 Mar;8(328):328ra29 PMID: 26936506

Karuppagounder SS, Kumar A, Shao DS, Zille M, Bourassa MW, Caulfield JT, Alim I, Ratan RR (2015). Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases Brain Res. 2015 Dec;1628(Pt B):273-87 PMID: 26232572

Sleiman SF, Olson DE, Bourassa MW, Karuppagounder SS, Zhang YL, Gale J, Wagner FF, Basso M, Coppola G, Pinto JT, Holson EB, Ratan RR (2014). Hydroxamic acid-based histone deacetylase (HDAC) inhibitors can mediate neuroprotection independent of HDAC inhibition J. Neurosci. 2014 Oct;34(43):14328-37 PMID: 25339746

Karuppagounder SS, Ratan RR (2012). Hypoxia-inducible factor prolyl hydroxylase inhibition: robust new target or another big bust for stroke therapeutics? J. Cereb. Blood Flow Metab. 2012 Jul;32(7):1347-61 PMID: 22415525

Gibson GE, Karuppagounder SS, Shi Q (2008). Oxidant-induced changes in mitochondria and calcium dynamics in the pathophysiology of Alzheimer's disease Ann. N. Y. Acad. Sci. 2008 Dec;1147:221-32 PMID: 19076444

Karuppagounder SS, Pinto JT, Xu H, Chen HL, Beal MF, Gibson GE (2009). Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease Neurochem. Int. 2009 Feb;54(2):111-8 PMID: 19041676

Karuppagounder SS, Xu H, Shi Q, Chen LH, Pedrini S, Pechman D, Baker H, Beal MF, Gandy SE, Gibson GE (2009). Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model Neurobiol. Aging 2009 Oct;30(10):1587-600 PMID: 18406011

Karuppagounder SS, Xu H, Pechman D, Chen LH, DeGiorgio LA, Gibson GE (2008). Translocation of amyloid precursor protein C-terminal fragment(s) to the nucleus precedes neuronal death due to thiamine deficiency-induced mild impairment of oxidative metabolism Neurochem. Res. 2008 Jul;33(7):1365-72 PMID: 18317926

Shi Q, Karuppagounder SS, Xu H, Pechman D, Chen H, Gibson GE (2007). Responses of the mitochondrial alpha-ketoglutarate dehydrogenase complex to thiamine deficiency may contribute to regional selective vulnerability Neurochem. Int. 2007 Jun;50(7-8):921-31 PMID: 17482317

Karuppagounder SS, Shi Q, Xu H, Gibson GE (2007). Changes in inflammatory processes associated with selective vulnerability following mild impairment of oxidative metabolism Neurobiol. Dis. 2007 May;26(2):353-62 PMID: 17398105