Helena Parfenova, Ph.D.
956 Court Ave
Memphis, TN 38163
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, hypoxia, 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.
- Parfenova H, Carratu P, Tcheranova D, Fedinec A, Pourcyrous M, 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, Leffler CW. Cerebroprotective functions of HO-2. Curr Pharm Des 14: 443–53, 2008.
- Basuroy S, Bhattacharya S, Leffler CW, Parfenova H. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-a in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 296: C422–32, 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: H1687–98, 2010.
- Harsono M, Pourcyrous M, Jolly EJ, de Jongh Curry A, Fedinec AL, Liu J, Basuroy S, Zhuang D, Leffler CW, Parfenova H. Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity. Am J Physiol Heart Circ Physiol 311: H1202-H1213, 2016.