ELENA PARFENOVA, Ph.D.

Professor
Physiology

Office: E332A COLEMAN BUILDING
956 COURT AVENUE
MEMPHIS TN 381632116
Tel: (901) 448-8319
hparfeno@uthsc.edu

Education

  • Ph.D., , Biochemical Cytology
  • Ph.D., The Institute of Cytology Acad. Sci., USSR, Biochemical Cytology
  • M.S., Leningrad State University, Russia, Sciences
  • M.S., Leningrad State University, Russia (MS)

Research description

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 brain endothelial dilator function, and subsequent loss of cerebral blood flow autoregulation. Glutamate, a major excitatory neurotransmitter, and TNF-a, 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.

Research interest/specialty

We investigate the roles of heme oxygenase (HO) and carbon monoxide (CO).

Research interest/specialty

We investigate the roles of heme oxygenase (HO) and carbon monoxide (CO).

Research description

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 brain endothelial dilator function, and subsequent loss of cerebral blood flow autoregulation. Glutamate, a major excitatory neurotransmitter, and TNF-a, 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.

Publications

  1. Parfenova, H, Leffler, CW. Cerebroprotective functions of HO-2. Curr Pharm Des, 14 (5), 443-53, 2008.
  2. Zimmermann, A, Leffler, CW, Tcheranova, D, Fedinec, AL, Parfenova, H. Cerebroprotective effects of the CO-releasing molecule CORM-A1 against seizure-induced neonatal vascular injury. Am J Physiol Heart Circ Physiol, 293 (4), H2501-7, 2007.
  3. Leffler, CW, Parfenova, H, Fedinec, AL, Basuroy, S, Tcheranova, D. Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs. Am J Physiol Heart Circ Physiol, 291 (6), H2897-904, 2006.
  4. Basuroy, S, Bhattacharya, S, Tcheranova, D, Qu, Y, Regan, RF, Leffler, CW, Parfenova, H. HO-2 provides endogenous protection against oxidative stress and apoptosis caused by TNF-alpha in cerebral vascular endothelial cells. Am J Physiol Cell Physiol, 291 (5), C897-908, 2006.
  5. Parfenova, H, Basuroy, S, Bhattacharya, S, Tcheranova, D, Qu, Y, Regan, RF, 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 (5), C1399-410, 2006.
  6. Leffler, CW, Parfenova, H, Jaggar, JH, Wang, R. Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation. J Appl Physiol, 100 (3), 1065-76, 2006.
  7. Leffler, CW, Balabanova, L, Fedinec, AL, Parfenova, H. Nitric oxide increases carbon monoxide production by piglet cerebral microvessels. Am J Physiol Heart Circ Physiol, 289 (4), H1442-7, 2005.
  8. 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 (8), 805-12, 2005.
  9. Leffler, CW, Fedinec, AL, Parfenova, H, Jaggar, JH. Permissive contributions of NO and prostacyclin in CO-induced cerebrovascular dilation in piglets. Am J Physiol Heart Circ Physiol, 289 (1), H432-8, 2005.
  10. 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 Circ Physiol, 288 (6), H2843-50, 2005.
  11. Pourcyrous, M, Bada, HS, Blaho, KE, Randolph, MM, Parfenova, H, Mandrell, TD, Arheart, K, Korones, SB, Leffler, CW. Chronic prenatal exposure to cocaine alters cerebrovascular responses in newborn pigs. Exp Biol Med (Maywood), 229 (8), 819-25, 2004.
  12. Parfenova, H, Daley, ML, Carratu, P, Leffler, CW. Heme oxygenase inhibition reduces neuronal activation evoked by bicuculline in newborn pigs. Brain Res, 1014 (1-2), 87-96, 2004.
  13. Xi, Q, Tcheranova, D, Parfenova, H, Horowitz, B, Leffler, CW, Jaggar, JH. Carbon monoxide activates KCa channels in newborn arteriole smooth muscle cells by increasing apparent Ca2+ sensitivity of alpha-subunits. Am J Physiol Heart Circ Physiol, 286 (2), H610-8, 2004.
  14. Carratu, P, Pourcyrous, M, Fedinec, A, Leffler, CW, Parfenova, H. Endogenous heme oxygenase prevents impairment of cerebral vascular functions caused by seizures. Am J Physiol Heart Circ Physiol, 285 (3), H1148-57, 2003.
  15. Leffler, CW, Balabanova, L, Sullivan, CD, Wang, X, Fedinec, AL, Parfenova, H. Regulation of CO production in cerebral microvessels of newborn pigs. Am J Physiol Heart Circ Physiol, 285 (1), H292-7, 2003.
  16. Leffler, CW, Balabanova, L, Fedinec, AL, Waters, CM, Parfenova, H. Mechanism of glutamate stimulation of CO production in cerebral microvessels. Am J Physiol Heart Circ Physiol, 285 (1), H74-80, 2003.
  17. Fiumana, E, Parfenova, H, Jaggar, JH, Leffler, CW. Carbon monoxide mediates vasodilator effects of glutamate in isolated pressurized cerebral arterioles of newborn pigs. Am J Physiol Heart Circ Physiol, 284 (4), H1073-9, 2003.
  18. Parfenova, H, Fedinec, A, Leffler, CW. Ionotropic glutamate receptors in cerebral microvascular endothelium are functionally linked to heme oxygenase. J Cereb Blood Flow Metab, 23 (2), 190-7, 2003.
  19. Parfenova, H, Levine, V, Gunther, WM, Pourcyrous, M, Leffler, CW. COX-1 and COX-2 contributions to basal and IL-1 beta-stimulated prostanoid synthesis in human neonatal cerebral microvascular endothelial cells. Pediatr Res, 52 (3), 342-8, 2002.
  20. Pourcyrous, M, Bada, HS, Parfenova, H, Daley, ML, Korones, SB, Leffler, CW. Cerebrovasodilatory contribution of endogenous carbon monoxide during seizures in newborn pigs. Pediatr Res, 51 (5), 579-85, 2002.
  21. Parfenova, H, Neff, RA, Alonso, JS, Shlopov, BV, Jamal, CN, Sarkisova, SA, Leffler, CW. Cerebral vascular endothelial heme oxygenase: expression, localization, and activation by glutamate. Am J Physiol Cell Physiol, 281 (6), C1954-63, 2001.
  22. Parfenova, H, Parfenov, VN, Shlopov, BV, Levine, V, Falkos, S, Pourcyrous, M, Leffler, CW. Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells. Am J Physiol Cell Physiol, 281 (1), C166-78, 2001.
  23. Levine, V, Pourcyrous, M, Bada, HS, Parfenova, H, Yang, W, Korones, SB, Leffler, CW. Preservation of cerebrovascular tone and reactivity by sodium channel inhibition in experimental prolonged asphyxia in piglets. Pediatr Res, 47 (3), 376-80, 2000.
  24. Parfenova, H, Massie, V, Leffler, CW. Developmental changes in endothelium-derived vasorelaxant factors in cerebral circulation. Am J Physiol Heart Circ Physiol, 278 (3), H780-8, 2000.
  25. Parkinson, PA, Parfenova, H, Leffler, CW. Phospholipase C activation by prostacyclin receptor agonist in cerebral microvascular smooth muscle cells. Proc Soc Exp Biol Med, 223 (1), 53-8, 2000.
  26. Parfenova, H, Haffner, J, Leffler, CW. Phosphorylation-dependent stimulation of prostanoid synthesis by nigericin in cerebral endothelial cells. Am J Physiol, 277 (4 Pt 1), C728-38, 1999.
  27. Parfenova, H, Fedinec, A, Leffler, CW. Role of tyrosine phosphorylation in the regulation of cerebral vascular tone in newborn pig in vivo. Am J Physiol, 276 (1 Pt 2), H185-93, 1999.
  28. Pourcyrous, M, Bada, HS, Yang, W, Parfenova, H, Wong, SP, Korones, SB, Leffler, CW. Prognostic significance of cerebrospinal fluid cyclic adenosine monophosphate in neonatal asphyxia. J Pediatr, 134 (1), 90-6, 1999.
  29. Parfenova, H, Balabanova, L, Leffler, CW. Posttranslational regulation of cyclooxygenase by tyrosine phosphorylation in cerebral endothelial cells. Am J Physiol, 274 (1 Pt 1), C72-81, 1998.
  30. Pourcyrous, M, Parfenova, H, Shibata, M, Bada, HS, Korones, SB, Leffler, CW. The effects of intraventricular/periventricular blood on cerebral 3',5'-cyclic adenosine monophosphate concentration and cerebrovascular reactivity in newborn pigs. Pediatr Res, 42 (3), 305-10, 1997.
  31. Parfenova, H, Eidson, TH, Leffler, CW. Upregulation of COX-2 in cerebral microvascular endothelial cells by smooth muscle cell signals. Am J Physiol, 273 (1 Pt 1), C277-88, 1997.
  32. Pourcyrous, M, Parfenova, H, Bada, HS, Korones, SB, Leffler, CW. Changes in cerebral cyclic nucleotides and cerebral blood flow during prolonged asphyxia and recovery in newborn pigs. Pediatr Res, 41 (5), 617-23, 1997.
  33. Leffler, CW, Smith, JS, Edrington, JL, Zuckerman, SL, Parfenova, H. Mechanisms of hypoxia-induced cerebrovascular dilation in the newborn pig. Am J Physiol, 272 (3 Pt 2), H1323-32, 1997.
  34. Leffler, CW, Parfenova, H. Cerebral arteriolar dilation to hypoxia: role of prostanoids. Am J Physiol, 272 (1 Pt 2), H418-24, 1997.
  35. Rama, GP, Parfenova, H, Leffler, CW. Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs. Pediatr Res, 41 (1), 83-9, 1997.
  36. Shibata, M, Parfenova, H, Zuckerman, SL, Seyer, JM, Krueger, JM, Leffler, CW. Interleukin-1 beta peptides induce cerebral pial arteriolar dilation in anesthetized newborn pigs. Am J Physiol, 270 (5 Pt 2), R1044-50, 1996.
  37. Parfenova, H, Leffler, CW. Effects of hypercapnia on prostanoid and cAMP production by cerebral microvascular cell cultures. Am J Physiol, 270 (5 Pt 1), C1503-10, 1996.
  38. Shibata, M, Parfenova, H, Zuckerman, SL, Leffler, CW. Tumor necrosis factor-alpha induces pial arteriolar dilation in newborn pigs. Brain Res Bull, 39 (4), 241-7, 1996.
  39. Parfenova, H, Zuckerman, S, Leffler, CW. Inhibitory effect of indomethacin on prostacyclin receptor-mediated cerebral vascular responses. Am J Physiol, 268 (5 Pt 2), H1884-90, 1995.
  40. Parfenova, H, Leffler, CW. Functional study on vasodilator effects of prostaglandin E2 in the newborn pig cerebral circulation. Eur J Pharmacol, 278 (2), 133-42, 1995.
  41. Tigyi, G, Hong, L, Yakubu, M, Parfenova, H, Shibata, M, Leffler, CW. Lysophosphatidic acid alters cerebrovascular reactivity in piglets. Am J Physiol, 268 (5 Pt 2), H2048-55, 1995.
  42. Albuquerque, ML, Lowery-Smith, L, Hsu, P, Parfenova, H, Leffler, CW. Low CO2 stimulates inositol phosphate turnover and increased inositol 1,4,5-trisphosphate levels in piglet cerebral microvascular smooth muscle cells. Proc Soc Exp Biol Med, 209 (1), 14-9, 1995.
  43. Parfenova, H, Hsu, P, Leffler, CW. Dilator prostanoid-induced cyclic AMP formation and release by cerebral microvascular smooth muscle cells: inhibition by indomethacin. J Pharmacol Exp Ther, 272 (1), 44-52, 1995.
  44. Armstead, WM, Zuckerman, SL, Shibata, M, Parfenova, H, Leffler, CW. Different pial arteriolar responses to acetylcholine in the newborn and juvenile pig. J Cereb Blood Flow Metab, 14 (6), 1088-95, 1994.
  45. Parfenova, H, Shibata, M, Zuckerman, S, Leffler, CW. CO2 and cerebral circulation in newborn pigs: cyclic nucleotides and prostanoids in vascular regulation. Am J Physiol, 266 (4 Pt 2), H1494-501, 1994.
  46. Parfenova, H, Shibata, M, Zuckerman, S, Mirro, R, Leffler, CW. Cyclic nucleotides and cerebrovascular tone in newborn pigs. Am J Physiol, 265 (6 Pt 2), H1972-82, 1993.
  47. Parfenova, H, Shibata, M, Leffler, CW. Subarachnoid blood causes pial arteriolar constriction in newborn pigs. Stroke, 24 (11), 1729-34, 1993.
  48. Tong, S, Parfenova, H, Shibata, M, Zuckerman, S, Armstead, WM, Leffler, CW. Pituitary adenylate cyclase-activating polypeptide dilates cerebral arterioles of newborn pigs. Proc Soc Exp Biol Med, 203 (3), 343-7, 1993.
  49. Leffler, CW, Mirro, R, Shibata, M, Parfenova, H, Armstead, WM, Zuckerman, S. Effects of indomethacin on cerebral vasodilator responses to arachidonic acid and hypercapnia in newborn pigs. Pediatr Res, 33 (6), 609-14, 1993.