Helena Parfenova, Ph.D.
1971 M.S. (Biology), Leningrad State University, St Petesrburg, Russia
1975 Ph.D. (Cell Physiology), Institute of Cytology, St Petesrburg, Russia
We investigate the roles of heme oxygenase (HO) and carbon monoxide (CO), the HO-derived endogenous gaseous mediator, in regulating blood flow to the brain and in promoting survival of brain endothelial cells during cerebral vascular insult caused by seizures and oxidative stress. Seizures cause sustained cerebral vascular injury, reduction of endothelial vasodilator function, and loss of cerebral blood flow regulation. Glutamate, an excitatory neurotransmitter, and TNFa, a pro-inflammatory cytokine, are major injurious factors involved in the pathogenesis of seizure-induced cerebral vascular injury and endothelial apoptosis. Activation of endogenous HO/CO system or pharmacological delivery of CO to the brain reduces or prevents cerebral vascular endothelial injury and restores cerebral vascular endothelial function.
We investigate the HO/CO system as a critical component of anti-apoptotic mechanisms involved in protecting the brain from cerebral vascular injury caused by seizures and oxidative stress. The projects involve in vivo and in vitro studies in newborn pigs using the closed cranial window techniques for detection of cerebral blood flow responses, isolated cerebral resistance arterioles, and primary cultures of cerebral vascular endothelial, smooth muscle, and glial cells. My ultimate goal is to translate the knowledge gained from the animal models to pediatric practice to correct the deteriorating neurological outcome of neonatal cerebrovascular insults
- Heme Oxygenase and Cerebral Vascular Injury. NIHLBI/NIH. 6/1/4-5/31/14. P.I.
- Cerebrovascular Stress and Circulating Endothelial Cells. NINDS/NIHLBI. 2/1/10-1/31/15 P.I.
- Control of neonatal circulation. NHLBI/NIH. 4/1/1984-3/31/2017 (Co-I, CW Leffler, P.I.)
- Hydrogen Sulfide in Newborn Cerebral Circulation. NIHLBI/NIH. 8/1/1990-7/31/2015 (Co-I, CW Leffler, P.I.)
- Parfenova H, Carratu P, Tcheranova D, Fedinec A, Pourcyrous M, and Leffler CW. Epileptic seizures cause extended postictal cerebral vascular dysfunction that is prevented by HO-1 overexpression. Am J Physiol Heart Physiol 288: 2843-50, 2005.
- Jaggar JH, Li A, Parfenova H, Liu J, Umstot ES, Dopico AM, Leffler CW. Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels. Circ Res 97: 805–12, 2005.
- Parfenova H, Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, and Leffler CW. Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection. Am J Physiol Cell Physiol 290: C1399-410, 2006.
- Basuroy S, Bhattacharya S, Tcheranova D, Qu Y, Regan RF, Leffler CW, and Parfenova H. Heme oxygenase-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-a in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 291: C897-908, 2006.
- Leffler CW, Parfenova H, Fedinec AL, Basuroy S, and Tcheranova D. Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs. Am J Physiol Heart Circ Physiol 291: H2897-2904, 2006.
- Parfenova H, Leffler CW. Cerebroprotective functions of HO-2. Curr Pharm Des 14:443-53, 2008.
- Basuroy S, Bhattacharya S, Leffler CW, and Parfenova H. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF? in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 296: C422-C432, 2009.
- Parfenova H, Leffler CW, Tcheranova D, Basuroy S, Zimmermann A. Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage. Am J Physiol Heart Circ Physiol 298: H1687-H1698, 2010.
- Basuroy S, Tcheranova D, Bhattacharya S, Leffler CW, Parfenova H. Nox4 NADPH oxidase–derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-a-induced apoptosis. Am J Physiol Cell Physiol 300: C256-65, 2011.
- Leffler CW, Parfenova H, Basuroy S, Jaggar JH, Umstot ES, Fedinec AL. Hydrogen sulfide and cerebral microvascular tone in newborn pigs. Am J Physiol Heart Circ Physiol 300: H440–56, 2011.
- Leffler CW, Parfenova H, Jaggar J. Carbon monoxide as an endogenous cerebrovascular modulator. Am J Physiol Heart Circ Physiol 301: H1–11, 2011
- Parfenova H, Leffler CW, Basuroy S, Liu J, Fedinec AL. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J Cereb Blood Flow Metab 32: 1024–34, 2012.
- Parfenova H, Tcheranova D, Basuroy S, Fedinec AL, Liu J, Leffler CW. Functional role of astrocyte glutamate receptors and carbon monoxide in cerebral vasodilation response to glutamate. Am J Physiol Heart Circ Physiol 302: H2257–66, 2012.
- Basuroy S, Leffler CW, Parfenova H. CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis. Am J Physiol Cell Physiol 304: C1105-C1115, 2013.