Rona Giffard

Administrative Appointments

• Vice-Chair for Research, Dept. of Anesthesia , (1999– present )

Honors and Awards

• NIH Clinical Investigator Award, NIH (1990-1995)
• Young Investigator Award, Foundation for Anesthesia Education and Research (1991-1992)
• Ellen Weaver Award, Association for Women in Science, Northern California Chapters (1997)
• Frontiers in Anesthesia Research Award, International Anesthesia Research Society (1998-2003)
• AHA/Bugher Award, American Heart Association (2000-2004)

Professional Education

• Ph.D., StanfordUniversity Structural Biology
• M.D., Stanford University Medicine

Postdoctoral Advisees

• George Barreto, Yajing Hu, Ludmila Voloboueva, Xiaoxing Xiong

Graduate & Fellowship Program Affiliations

• Anesthesia
• Neurosciences
• Neurosurgery
• Neonatology and Developmental Biology
• Cell Biology
• Molecular and Genetic Medicine

Web Site Links

• Giffard Lab Web site

Research Interests

Brain injury from stroke, head trauma, and chronic neurologic degenerative diseases, is a major cause of morbidity and mortality. We are particularly interested in the cellular consequences of brain injury. To study this problem we work with primary cultures of neurons and astrocytes from mice in addition to employing rodent models of stroke. Current work focuses on: 1) the role of astrocytes in brain injury; 2) the interaction of neurons and glia during injury; 3) protection using heat shock protein and anti-apoptotic protein overexpression 4) changes in mitochondrial function and signaling in injury; 5) the interaction of oxidative stress and inflammation in stroke; 6) computational modeling of cell death.
We use gene transfer techniques to express genes of interest in brain cells and intact brain and analyze ways in which these genes can provide protection. We use fluorescent probes for pH, intracellular calcium, ROS, mitochondrial membrane potential, glutathione, as well as morphologically evaluate outcome, and quantitate injury. We also use transgenic mice to analyze the effects of overexpression or loss of expression of specific genes on outcome from stroke. Mitochondria are central to both energy metabolism and the regulation of cell death. We study changes in mitochondria with stress. We are also interested in the interaction of oxidative stress and inflammation in stroke.

A new area for us is computational modeling of cell death and the effects of heat shock proteins. We are working on an ODE control model.

Publications

• Postischemic brain injury is attenuated in mice lacking the beta2-adrenergic receptor. Han RQ,  Ouyang YB, Xu L, Agrawal R, Patterson AJ, Giffard RG.  Anesth Analg.  2009; 108 (1): 280-7
• Inflammation and NFkappaB activation is decreased by hypothermia following global cerebral ischemia. Webster CM,  Kelly S, Koike MA, Chock VY, Giffard RG, Yenari MA.  Neurobiol Dis.  2009; 33 (2): 301-12
• Overexpression of mitochondrial Hsp70/Hsp75 in rat brain protects mitochondria, reduces oxidative stress, and protects from focal ischemia. Xu L,  Voloboueva LA, Ouyang Y, Emery JF, Giffard RG.  J Cereb Blood Flow Metab.  2009; 29 (2): 365-74
• Overexpression of mitochondrial Hsp70/Hsp75 protects astrocytes against ischemic injury in vitro. Voloboueva LA,  Duan M, Ouyang Y, Emery JF, Stoy C, Giffard RG.  J Cereb Blood Flow Metab.  2008; 28 (5): 1009-16
• Regulation of apoptotic and inflammatory cell signaling in cerebral ischemia: the complex roles of heat shock protein 70. Giffard RG,  Han RQ, Emery JF, Duan M, Pittet JF.  Anesthesiology.  2008; 109 (2): 339-48
• NOx and ADMA changes with focal ischemia, amelioration with the chaperonin GroEL. Xu L,  Wang B, Kaur K, Kho MF, Cooke JP, Giffard RG.  Neurosci Lett.  2007; 418 (2): 201-4
• Inhibition of mitochondrial function in astrocytes: implications for neuroprotection. Voloboueva LA,  Suh SW, Swanson RA, Giffard RG.  J Neurochem.  2007; 102 (4): 1383-94
• Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed neuronal damage after transient forebrain ischemia. Ouyang YB,  Voloboueva LA, Xu LJ, Giffard RG.  J Neurosci.  2007; 27 (16): 4253-60
• Regulation of the rat brain Na+ -driven Cl-/HCO3 - exchanger involves protein kinase A and a multiprotein signaling complex. Lee YS,  Ouyang YB, Giffard RG.  FEBS Lett.  2006; 580 (20): 4865-71
• Overexpression of inducible heat shock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucose deprivation stress. Ouyang YB,  Xu LJ, Sun YJ, Giffard RG.  Cell Stress Chaperones.  2006; 11 (2): 180-6
• Antegrade cerebral perfusion reduces apoptotic neuronal injury in a neonatal piglet model of cardiopulmonary bypass. Chock VY,  Amir G, Davis CR, Ramamoorthy C, Riemer RK, Ray D, Giffard RG, Reddy VM.  J Thorac Cardiovasc Surg.  2006; 131 (3): 659-65
• Biphasic role of nuclear factor-kappa B on cell survival and COX-2 expression in SOD1 Tg astrocytes after oxygen glucose deprivation. Lee YS,  Song YS, Giffard RG, Chan PH.  J Cereb Blood Flow Metab.  2006; 26 (8): 1076-88
• The carboxyl-terminal domain of inducible Hsp70 protects from ischemic injury in vivo and in vitro. Sun Y,  Ouyang YB, Xu L, Chow AM, Anderson R, Hecker JG, Giffard RG.  J Cereb Blood Flow Metab.  2006; 26 (7): 937-50
• Chaperonin GroEL and its mutant D87K protect from ischemia in vivo and in vitro. Xu L,  Dayal M, Ouyang YB, Sun Y, Yang CF, Frydman J, Giffard RG.  Neurobiol Aging.  2006; 27 (4): 562-9
• Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Yenari MA,  Xu L, Tang XN, Qiao Y, Giffard RG.  Stroke.  2006; 37 (4): 1087-93
• Development of neonatal murine microglia in vitro: changes in response to lipopolysaccharide and ischemia-like injury. Chock VY,  Giffard RG.  Pediatr Res.  2005; 57 (4): 475-80
• Overexpression of copper/zinc superoxide dismutase decreases ischemia-like astrocyte injury. Wang J,  Ma JH, Giffard RG.  Free Radic Biol Med.  2005; 38 (8): 1112-8
• Ischemia-induced programmed cell death in astrocytes. Giffard RG,  Swanson RA.  Glia.  2005; 50 (4): 299-306
• Geldanamycin treatment reduces delayed CA1 damage in mouse hippocampal organotypic cultures subjected to oxygen glucose deprivation. Ouyang YB,  Xu L, Giffard RG.  Neurosci Lett.  2005; 380 (3): 229-33
• Antiapoptotic and anti-inflammatory mechanisms of heat-shock protein protection. Yenari MA,  Liu J, Zheng Z, Vexler ZS, Lee JE, Giffard RG.  Ann N Y Acad Sci.  2005; 1053 74-83
• Cellular neuroprotective mechanisms in cerebral ischemia: Bcl-2 family proteins and protection of mitochondrial function. Ouyang YB,  Giffard RG.  Cell Calcium.  2004 Sep-Oct; 36 (3-4): 303-11
• Changes in astrocyte mitochondrial function with stress: effects of Bcl-2 family proteins. Ouyang YB,  Giffard RG.  Neurochem Int.  2004 Jul-Aug; 45 (2-3): 371-9
• Effect of overexpression of protective genes on mitochondrial function of stressed astrocytes. Giffard R,  Ouyang Y.  J Bioenerg Biomembr.  2004; 36 (4): 313-5
• Susceptibility to apoptosis varies with time in culture for murine neurons and astrocytes: changes in gene expression and activity. Xu L,  Chock VY, Yang EY, Giffard RG.  Neurol Res.  2004; 26 (6): 632-43
• Chaperones, protein aggregation, and brain protection from hypoxic/ischemic injury. Giffard RG,  Xu L, Zhao H, Carrico W, Ouyang Y, Qiao Y, Sapolsky R, Steinberg G, Hu B, Yenari MA.  J Exp Biol.  2004; 207 (Pt 18): 3213-20
• Cell-specific role for epsilon- and betaI-protein kinase C isozymes in protecting cortical neurons and astrocytes from ischemia-like injury. Wang J,  Bright R, Mochly-Rosen D, Giffard RG.  Neuropharmacology.  2004; 47 (1): 136-45
• Many mechanisms for hsp70 protection from cerebral ischemia. Giffard RG,  Yenari MA.  J Neurosurg Anesthesiol.  2004; 16 (1): 53-61
• Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Kim JH,  Yenari MA, Giffard RG, Cho SW, Park KA, Lee JE.  Exp Neurol.  2004; 189 (1): 122-30
• The 70 kDa heat shock protein suppresses matrix metalloproteinases in astrocytes. Lee JE,  Kim YJ, Kim JY, Lee WT, Yenari MA, Giffard RG.  Neuroreport.  2004; 15 (3): 499-502
• Perinatal brain injury: the role of development in vulnerability. Giffard RG,  Fiskum G.  Anesthesiology.  2003; 98 (5): 1039-41
• Overexpression of HDJ-2 protects astrocytes from ischemia-like injury and reduces redistribution of ubiquitin staining in vitro. Qiao Y,  Ouyang YB, Giffard RG.  J Cereb Blood Flow Metab.  2003; 23 (10): 1113-6
• Geldanamycin reduces necrotic and apoptotic injury due to oxygen-glucose deprivation in astrocytes. Xu L,  Ouyang YB, Giffard RG.  Neurol Res.  2003; 25 (7): 697-700
• Bcl-XL maintains mitochondrial function in murine astrocytes deprived of glucose. Ouyang YB,  Giffard RG.  J Cereb Blood Flow Metab.  2003; 23 (3): 275-9
• Gene therapy and hypothermia for stroke treatment. Yenari MA,  Zhao H, Giffard RG, Sobel RA, Sapolsky RM, Steinberg GK.  Ann N Y Acad Sci.  2003; 993 54-68; discussion 79-81
• Two variants of the rat brain sodium-driven chloride bicarbonate exchanger (NCBE): developmental expression and addition of a PDZ motif. Giffard RG,  Lee YS, Ouyang YB, Murphy SL, Monyer H.  Eur J Neurosci.  2003; 18 (11): 2935-45
• Advances in understanding protection from cerebral ischemia. Giffard RG,  Jaffe RA.  Curr Opin Anaesthesiol.  2002; 15 (5): 495-500
• Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. Xu L,  Yenari MA, Steinberg GK, Giffard RG.  J Cereb Blood Flow Metab.  2002; 22 (1): 21-8
• Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. Han HS,  Qiao Y, Karabiyikoglu M, Giffard RG, Yenari MA.  J Neurosci.  2002; 22 (10): 3921-8
• Effect of Bcl-x(L) overexpression on reactive oxygen species, intracellular calcium, and mitochondrial membrane potential following injury in astrocytes. Ouyang YB,  Carriedo SG, Giffard RG.  Free Radic Biol Med.  2002; 33 (4): 544-51
• Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2. Kelly S,  Zhang ZJ, Zhao H, Xu L, Giffard RG, Sapolsky RM, Yenari MA, Steinberg GK.  Ann Neurol.  2002; 52 (2): 160-7
• Caspase inhibitors reduce the apoptotic but not necrotic component of kainate injury in primary murine cortical neuronal cultures. Glassford A,  Lee JE, Xu L, Giffard RG.  Neurol Res.  2002; 24 (8): 796-800
• UV-vulnerability of human papilloma virus type-16 E7-expressing astrocytes is associated with mitochondrial membrane depolarization and caspase-3 activation. Lee WT,  Lee SH, Carriedo SG, Giffard RG, Yoon YJ, Kim JH, Park KA, Lee JE.  Mol Cells.  2002; 14 (2): 288-94
• Neuroprotective effects of bcl-2 overexpression in hippocampal cultures: interactions with pathways of oxidative damage. Howard S,  Bottino C, Brooke S, Cheng E, Giffard RG, Sapolsky R.  J Neurochem.  2002; 83 (4): 914-23
• Ischemic vulnerability of primary murine microglial cultures. Yenari MA,  Giffard RG.  Neurosci Lett.  2001; 298 (1): 5-8
• Differential sensitivity of murine astrocytes and neurons from different brain regions to injury. Xu L,  Sapolsky RM, Giffard RG.  Exp Neurol.  2001; 169 (2): 416-24
• Differential neuroprotection from human heat shock protein 70 overexpression in in vitro and in vivo models of ischemia and ischemia-like conditions. Lee JE,  Yenari MA, Sun GH, Xu L, Emond MR, Cheng D, Steinberg GK, Giffard RG.  Exp Neurol.  2001; 170 (1): 129-39
• Overexpression of HSP72 after induction of experimental stroke protects neurons from ischemic damage. Hoehn B,  Ringer TM, Xu L, Giffard RG, Sapolsky RM, Steinberg GK, Yenari MA.  J Cereb Blood Flow Metab.  2001; 21 (11): 1303-9
• Human papilloma virus type 16 E7 genes protect astrocytes against apoptotic and necrotic death induced by hydrogen peroxide. Lee WT,  Lee JE, Lee SH, Jang HS, Giffard RG, Park KA.  Yonsei Med J.  2001; 42 (5): 471-9
• Cell death in the central nervous system: therapeutic possibilities? Giffard RG,  Morgan RL.  Reg Anesth Pain Med.  2000 Jan-Feb; 25 (1): 22-5
• Principles of gene therapy: potential applications in the treatment of cerebral ischaemia. Papadopoulos MC,  Giffard RG, Bell BA.  Br J Neurosurg.  2000; 14 (5): 407-14
• The electrogenic sodium bicarbonate cotransporter: developmental expression in rat brain and possible role in acid vulnerability. Giffard RG,  Papadopoulos MC, van Hooft JA, Xu L, Giuffrida R, Monyer H.  J Neurosci.  2000; 20 (3): 1001-8
• An introduction to the changes in gene expression that occur after cerebral ischaemia. Papadopoulos MC,  Giffard RG, Bell BA.  Br J Neurosurg.  2000; 14 (4): 305-12
• Overexpression of bcl-xL protects astrocytes from glucose deprivation and is associated with higher glutathione, ferritin, and iron levels. Xu L,  Koumenis IL, Tilly JL, Giffard RG.  Anesthesiology.  1999; 91 (4): 1036-46
• The neuroprotective potential of heat shock protein 70 (HSP70). Yenari MA,  Giffard RG, Sapolsky RM, Steinberg GK.  Mol Med Today.  1999; 5 (12): 525-31
• Overexpression of bcl-2, bcl-XL or hsp70 in murine cortical astrocytes reduces injury of co-cultured neurons. Xu L,  Lee JE, Giffard RG.  Neurosci Lett.  1999; 277 (3): 193-7
• Acidosis reduces neuronal apoptosis. Xu L,  Glassford AJ, Giaccia AJ, Giffard RG.  Neuroreport.  1998; 9 (5): 875-9
• The E6 and E7 genes of human papilloma virus-type 16 protect primary astrocyte cultures from injury. Lee JE,  Kim CY, Giaccia AJ, Giffard RG.  Brain Res.  1998; 795 (1-2): 10-6
• Potentiation of murine astrocyte antioxidant defence by bcl-2: protection in part reflects elevated glutathione levels. Papadopoulos MC,  Koumenis IL, Xu L, Giffard RG.  Eur J Neurosci.  1998; 10 (4): 1252-60
• Two tips for users of Bullard Intubating Laryngoscope. Habibi A,  Bushell E, Jaffe RA, Giffard RG, Brock-Utne JG.  Anesth Analg.  1998; 87 (5): 1206-8
• Increasing vulnerability of astrocytes to oxidative injury with age despite constant antioxidant defenses. Papadopoulos MC,  Koumenis IL, Yuan TY, Giffard RG.  Neuroscience.  1998; 82 (3): 915-25
• Vulnerability to glucose deprivation injury correlates with glutathione levels in astrocytes. Papadopoulos MC,  Koumenis IL, Dugan LL, Giffard RG.  Brain Res.  1997; 748 (1-2): 151-6
• Selection of human cervical epithelial cells that possess reduced apoptotic potential to low-oxygen conditions. Kim CY,  Tsai MH, Osmanian C, Graeber TG, Lee JE, Giffard RG, DiPaolo JA, Peehl DM, Giaccia AJ.  Cancer Res.  1997; 57 (19): 4200-4
• HSP70 protects murine astrocytes from glucose deprivation injury. Xu L,  Giffard RG.  Neurosci Lett.  1997; 224 (1): 9-12
• Increased production of extracellular glutamate by the mitochondrial glutaminase following neuronal death. Newcomb R,  Sun X, Taylor L, Curthoys N, Giffard RG.  J Biol Chem.  1997; 272 (17): 11276-82
• Mechanism of heat shock protein 72 induction in primary cultured astrocytes after oxygen-glucose deprivation. Bergeron M,  Mivechi NF, Giaccia AJ, Giffard RG.  Neurol Res.  1996; 18 (1): 64-72
• Over-expression of HSP-70 protects astrocytes from combined oxygen-glucose deprivation. Papadopoulos MC,  Sun XY, Cao J, Mivechi NF, Giffard RG.  Neuroreport.  1996; 7 (2): 429-32
• Glia modulate the response of murine cortical neurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. Dugan LL,  Bruno VM, Amagasu SM, Giffard RG.  J Neurosci.  1995; 15 (6): 4545-55
• Activation of class II or III metabotropic glutamate receptors protects cultured cortical neurons against excitotoxic degeneration. Bruno V,  Battaglia G, Copani A, Giffard RG, Raciti G, Raffaele R, Shinozaki H, Nicoletti F.  Eur J Neurosci.  1995; 7 (9): 1906-13
• Ultrastructure of excitotoxic neuronal death in murine cortical culture. Regan RF,  Panter SS, Witz A, Tilly JL, Giffard RG.  Brain Res.  1995; 705 (1-2): 188-98
• Correlation of CGS 19755 neuroprotection against in vitro excitotoxicity and focal cerebral ischemia. Pérez-Pinzón MA,  Maier CM, Yoon EJ, Sun GH, Giffard RG, Steinberg GK.  J Cereb Blood Flow Metab.  1995; 15 (5): 865-76
• Neuroprotection by the N-methyl-D-aspartate receptor antagonist CGP 40116: in vivo and in vitro studies. Maier CM,  Sun GH, Kunis DM, Giffard RG, Steinberg GK.  J Neurochem.  1995; 65 (2): 652-9
• Neuroprotective effect of hypothermia in cortical cultures exposed to oxygen-glucose deprivation or excitatory amino acids. Bruno VM,  Goldberg MP, Dugan LL, Giffard RG, Choi DW.  J Neurochem.  1994; 63 (4): 1398-406
• Neuroprotective effects of glutamate antagonists and extracellular acidity. Kaku DA,  Giffard RG, Choi DW.  Science.  1993; 260 (5113): 1516-8
• Secobarbital attenuates excitotoxicity but potentiates oxygen-glucose deprivation neuronal injury in cortical cell culture. Giffard RG,  Weiss JH, Swanson RA, Choi DW.  J Cereb Blood Flow Metab.  1993; 13 (5): 803-10
• Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin. Monyer H,  Giffard RG, Hartley DM, Dugan LL, Goldberg MP, Choi DW.  Neuron.  1992; 8 (5): 967-73
• Extracellular alkalinity exacerbates injury of cultured cortical neurons. Giffard RG,  Weiss JH, Choi DW.  Stroke.  1992; 23 (12): 1817-21
• Acute brain injury, NMDA receptors, and hydrogen ions: observations in cortical cell cultures. Choi DW,  Monyer H, Giffard RG, Goldberg MP, Christine CW.  Adv Exp Med Biol.  1990; 268 501-4
• Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Giffard RG,  Monyer H, Christine CW, Choi DW.  Brain Res.  1990; 506 (2): 339-42
• Selective vulnerability of cultured cortical glia to injury by extracellular acidosis. Giffard RG,  Monyer H, Choi DW.  Brain Res.  1990; 530 (1): 138-41
• Neuronal calcium channels. Giffard RG,  Choi DW.  J Neurosurg Anesthesiol.  1989; 1 (4): 364-7
• Ca2+-dependent binding of severin to actin: a one-to-one complex is formed. Giffard RG,  Weeds AG, Spudich JA.  J Cell Biol.  1984; 98 (5): 1796-803
• Ca2+-sensitive isolation of a cortical actin matrix from Dictyostelium amoebae. Giffard RG,  Spudich JA, Spudich A.  J Muscle Res Cell Motil.  1983; 4 (1): 115-31