Pak H. Chan

Administrative Appointments

• Director of Research, Department of Neurosurgery, Stanford University School of Medicine , (1997– present )

Honors and Awards

• James R. Doty Professor of Neurosurgery and Neurosciences, Stanford University (2007)
• Mencius Type A & Type B Scholarships, Chinese University of Hong Kong (1960-1961)
• University Scientific Achievement Scholarship, Chinese University of Hong Kong (1962-1963)
• Jacob Javits Neuroscience Investigator Award, National Institutes of Health (1997-2004)
• Bugher Foundation Award, American Heart Association (2001-2004)
• Chairman, 22nd Princeton Conference on Cerebrovascular Disease (2000)
• President, National Neurotrauma Society (2000-2001)
• Member, Neurology A Study Section (1985-1989)
• Member, NINDS Neurological Disorders Program Project Review A Committee (1996-2000)
• Co-Chair, Neurovascular Protective Mechanisms, NINDS Stroke Progress Review Group (July 15-18, 2001)
• Member, NINDS Stroke Progress Review Group (January 6, 2003)
• Member, NIMH Board of Scientific Counselors (April 27-28, 2003)
• Invited Speaker and Participant, Spinal Cord Injury Workshop, National Academy of Sciences USA (May 24, 2004)
• Member, External Scientific Review Committee, Canadian Stroke Network (2004-present)
• Thomas Willis Award, American Stroke Association (2008)

Professional Education

• BS, Chinese University of Hong Kong Biology (1964)
• MA, UCLA Biochemistry (1970)
• PhD, UCLA Biology (1972)

Postdoctoral Advisees

• Hai Chen, Gab Seok Kim, Nobuya Okami, Hiroyuki Sakata, Hideyuki Yoshioka

Graduate & Fellowship Program Affiliations

• Neurosciences

Research Interests

My primary research interest is to understand the molecular and cellular mechanisms of cell death in the CNS following acute injuries such as ischemia and trauma and chronic neurodegenerative diseases. We focus on the role of oxidative stress, mitochondrial dysfunction, DNA damage and repair, various gene expressions (gene family of HSP72, Bcl-2, c-fos and COX-2) and various transcription factors (NF-kappaB, AP1, p53) in the pathogenesis of necrosis and/or apoptosis. Various transgenic and knockout mutant mice of CuZn-superoxide dismutase (SOD1) and mitochondrial manganese SOD (SOD2) have been generated to address the role of superoxide radicals in these cell death processes. In addition, human SOD1 transgenic rats have been established as a model for the study of oxidative mechanisms and acute and chronic CNS injuries. The long-term goal of our research is to derive therapeutic strategies at the cellular and molecular level to ameliorate cell death in CNS injuries.

Publications

• Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. Jung JE,  Kim GS, Narasimhan P, Song YS, Chan PH.  J Neurosci.  2009; 29 (21): 7003-14
• Faster recovery of cerebral perfusion in SOD1-overexpressed rats after cardiac arrest and resuscitation. Xu Y,  Liachenko SM, Tang P, Chan PH.  Stroke.  2009; 40 (7): 2512-8
• Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. Niizuma K,  Endo H, Chan PH.  J Neurochem.  2009; 109 Suppl 1 133-8
• Inhibition of NADPH oxidase is neuroprotective after ischemia-reperfusion. Chen H,  Song YS, Chan PH.  J Cereb Blood Flow Metab.  2009; 29 (7): 1262-72
• VEGF Stimulates the ERK 1/2 signaling pathway and apoptosis in cerebral endothelial cells after ischemic conditions. Narasimhan P,  Liu J, Song YS, Massengale JL, Chan PH.  Stroke.  2009; 40 (4): 1467-73
• Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia. Niizuma K,  Yoshioka H, Chen H, Kim GS, Jung JE, Katsu M, Okami N, Chan PH.  Biochim Biophys Acta.  2009;
• Potential role of PUMA in delayed death of hippocampal CA1 neurons after transient global cerebral ischemia. Niizuma K,  Endo H, Nito C, Myer DJ, Chan PH.  Stroke.  2009; 40 (2): 618-25
• The role of Akt signaling in oxidative stress mediates NF-kappaB activation in mild transient focal cerebral ischemia. Song YS,  Narasimhan P, Kim GS, Jung JE, Park EH, Chan PH.  J Cereb Blood Flow Metab.  2008; 28 (12): 1917-26
• Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A2 signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion. Nito C,  Kamada H, Endo H, Niizuma K, Myer DJ, Chan PH.  J Cereb Blood Flow Metab.  2008; 28 (10): 1686-96
• Induction of mmp-9 expression and endothelial injury by oxidative stress after spinal cord injury. Yu F,  Kamada H, Niizuma K, Endo H, Chan PH.  J Neurotrauma.  2008; 25 (3): 184-95
• Increased expression of a proline-rich Akt substrate (PRAS40) in human copper/zinc-superoxide dismutase transgenic rats protects motor neurons from death after spinal cord injury. Yu F,  Narasimhan P, Saito A, Liu J, Chan PH.  J Cereb Blood Flow Metab.  2008; 28 (1): 44-52
• The PIDDosome mediates delayed death of hippocampal CA1 neurons after transient global cerebral ischemia in rats. Niizuma K,  Endo H, Nito C, Myer DJ, Kim GS, Chan PH.  Proc Natl Acad Sci U S A.  2008; 105 (42): 16368-73
• Bad as a converging signaling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats. Kamada H,  Nito C, Endo H, Chan PH.  J Cereb Blood Flow Metab.  2007; 27 (3): 521-33
• Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. Suh SW,  Gum ET, Hamby AM, Chan PH, Swanson RA.  J Clin Invest.  2007; 117 (4): 910-8
• Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood-brain barrier dysfunction. Kamada H,  Yu F, Nito C, Chan PH.  Stroke.  2007; 38 (3): 1044-9
• Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling. Endo H,  Nito C, Kamada H, Yu F, Chan PH.  J Cereb Blood Flow Metab.  2007; 27 (5): 975-82
• Reduced oxidative stress promotes NF-kappaB-mediated neuroprotective gene expression after transient focal cerebral ischemia: lymphocytotrophic cytokines and antiapoptotic factors. Song YS,  Lee YS, Narasimhan P, Chan PH.  J Cereb Blood Flow Metab.  2007; 27 (4): 764-75
• Akt/GSK3beta survival signaling is involved in acute brain injury after subarachnoid hemorrhage in rats. Endo H,  Nito C, Kamada H, Yu F, Chan PH.  Stroke.  2006; 37 (8): 2140-6
• Interferon-beta fails to protect in a model of transient focal stroke. Maier CM,  Yu F, Nishi T, Lathrop SJ, Chan PH.  Stroke.  2006; 37 (4): 1116-9
• Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats. Endo H,  Kamada H, Nito C, Nishi T, Chan PH.  J Neurosci.  2006; 26 (30): 7974-83
• 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
• Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats. Endo H,  Nito C, Kamada H, Nishi T, Chan PH.  J Cereb Blood Flow Metab.  2006; 26 (12): 1479-89
• Mild hypoxia promotes survival and proliferation of SOD2-deficient astrocytes via c-Myc activation. Liu J,  Narasimhan P, Lee YS, Song YS, Endo H, Yu F, Chan PH.  J Neurosci.  2006; 26 (16): 4329-37
• Evaluating therapeutic targets for reperfusion-related brain hemorrhage. Maier CM,  Hsieh L, Crandall T, Narasimhan P, Chan PH.  Ann Neurol.  2006; 59 (6): 929-38
• Overexpression of SOD1 in transgenic rats attenuates nuclear translocation of endonuclease G and apoptosis after spinal cord injury. Yu F,  Sugawara T, Nishi T, Liu J, Chan PH.  J Neurotrauma.  2006; 23 (5): 595-603
• Epo protects SOD2-deficient mouse astrocytes from damage by oxidative stress. Liu J,  Narasimhan P, Song YS, Nishi T, Yu F, Lee YS, Chan PH.  Glia.  2006; 53 (4): 360-5
• Modulation of proline-rich akt substrate survival signaling pathways by oxidative stress in mouse brains after transient focal cerebral ischemia. Saito A,  Hayashi T, Okuno S, Nishi T, Chan PH.  Stroke.  2006; 37 (2): 513-7
• Mitochondrial translocation of p53 underlies the selective death of hippocampal CA1 neurons after global cerebral ischaemia. Endo H,  Saito A, Chan PH.  Biochem Soc Trans.  2006; 34 (Pt 6): 1283-6
• A new approach for the investigation of reperfusion-related brain injury. Maier CM,  Hsieh L, Crandall T, Narasimhan P, Chan PH.  Biochem Soc Trans.  2006; 34 (Pt 6): 1366-9
• Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Saito A,  Maier CM, Narasimhan P, Nishi T, Song YS, Yu F, Liu J, Lee YS, Nito C, Kamada H, Dodd RL, Hsieh LB, Hassid B, Kim EE, González M, Chan PH.  Mol Neurobiol.  2005; 31 (1-3): 105-16
• Overexpression of human copper/zinc-superoxide dismutase in transgenic animals attenuates the reduction of apurinic/apyrimidinic endonuclease expression in neurons after in vitro ischemia and after transient global cerebral ischemia. Narasimhan P,  Sugawara T, Liu J, Hayashi T, Noshita N, Chan PH.  J Neurochem.  2005; 93 (2): 351-8
• Modulation of p53 degradation via MDM2-mediated ubiquitylation and the ubiquitin-proteasome system during reperfusion after stroke: role of oxidative stress. Saito A,  Hayashi T, Okuno S, Nishi T, Chan PH.  J Cereb Blood Flow Metab.  2005; 25 (2): 267-80
• Akt/Bad signaling and motor neuron survival after spinal cord injury. Yu F,  Sugawara T, Maier CM, Hsieh LB, Chan PH.  Neurobiol Dis.  2005; 20 (2): 491-9
• Superoxide dismutase 1 overexpression reduces MCP-1 and MIP-1 alpha expression after transient focal cerebral ischemia. Nishi T,  Maier CM, Hayashi T, Saito A, Chan PH.  J Cereb Blood Flow Metab.  2005; 25 (10): 1312-24
• Damage to the endoplasmic reticulum and activation of apoptotic machinery by oxidative stress in ischemic neurons. Hayashi T,  Saito A, Okuno S, Ferrand-Drake M, Dodd RL, Chan PH.  J Cereb Blood Flow Metab.  2005; 25 (1): 41-53
• Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke. Chan PH,  Ann N Y Acad Sci.  2005; 1042 203-9
• Oxidative stress transiently decreases the IKK complex (IKKalpha, beta, and gamma), an upstream component of NF-kappaB signaling, after transient focal cerebral ischemia in mice. Song YS,  Lee YS, Chan PH.  J Cereb Blood Flow Metab.  2005; 25 (10): 1301-11
• Neuroprotection by hypoxic preconditioning involves oxidative stress-mediated expression of hypoxia-inducible factor and erythropoietin. Liu J,  Narasimhan P, Yu F, Chan PH.  Stroke.  2005; 36 (6): 1264-9
• Future targets and cascades for neuroprotective strategies. Chan PH,  Stroke.  2004; 35 (11 Suppl 1): 2748-50
• The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. Okuno S,  Saito A, Hayashi T, Chan PH.  J Neurosci.  2004; 24 (36): 7879-87
• Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1. Saito A,  Hayashi T, Okuno S, Nishi T, Chan PH.  Brain Res Mol Brain Res.  2004; 127 (1-2): 89-95
• Oxidative stress is associated with XIAP and Smac/DIABLO signaling pathways in mouse brains after transient focal cerebral ischemia. Saito A,  Hayashi T, Okuno S, Nishi T, Chan PH.  Stroke.  2004; 35 (6): 1443-8
• Matrix metalloproteinase-9 and myeloperoxidase expression: quantitative analysis by antigen immunohistochemistry in a model of transient focal cerebral ischemia. Maier CM,  Hsieh L, Yu F, Bracci P, Chan PH.  Stroke.  2004; 35 (5): 1169-74
• Oxidative injury to the endoplasmic reticulum in mouse brains after transient focal ischemia. Hayashi T,  Saito A, Okuno S, Ferrand-Drake M, Dodd RL, Chan PH.  Neurobiol Dis.  2004; 15 (2): 229-39
• Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell death after stroke: relationships with nerve growth factor. Saito A,  Narasimhan P, Hayashi T, Okuno S, Ferrand-Drake M, Chan PH.  J Neurosci.  2004; 24 (7): 1584-93
• Neuronal death/survival signaling pathways in cerebral ischemia. Sugawara T,  Fujimura M, Noshita N, Kim GW, Saito A, Hayashi T, Narasimhan P, Maier CM, Chan PH.  NeuroRx.  2004; 1 (1): 17-25
• Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Chan PH,  Neurochem Res.  2004; 29 (11): 1943-9
• Oxidative stress affects the integrin-linked kinase signaling pathway after transient focal cerebral ischemia. Saito A,  Hayashi T, Okuno S, Nishi T, Chan PH.  Stroke.  2004; 35 (11): 2560-5
• Oxidative damage to the endoplasmic reticulum is implicated in ischemic neuronal cell death. Hayashi T,  Saito A, Okuno S, Ferrand-Drake M, Dodd RL, Nishi T, Maier CM, Kinouchi H, Chan PH.  J Cereb Blood Flow Metab.  2003; 23 (10): 1117-28
• Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia. Sugawara T,  Chan PH.  Antioxid Redox Signal.  2003; 5 (5): 597-607
• Protective effects of superoxide dismutase against ischemia-reperfusion injury: development and application of a transgenic animal model. Klein MB,  Chan PH, Chang J.  Plast Reconstr Surg.  2003; 111 (1): 251-5; discussion 256-7
• Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. Hayashi T,  Noshita N, Sugawara T, Chan PH.  J Cereb Blood Flow Metab.  2003; 23 (2): 166-80
• Overexpression of copper/zinc superoxide dismutase in transgenic mice protects against neuronal cell death after transient focal ischemia by blocking activation of the Bad cell death signaling pathway. Saito A,  Hayashi T, Okuno S, Ferrand-Drake M, Chan PH.  J Neurosci.  2003; 23 (5): 1710-8
• Copper-zinc superoxide dismutase affects Akt activation after transient focal cerebral ischemia in mice. Noshita N,  Sugawara T, Lewén A, Hayashi T, Chan PH.  Stroke.  2003; 34 (6): 1513-8
• Role of superoxide in poly(ADP-ribose) polymerase upregulation after transient cerebral ischemia. Narasimhan P,  Fujimura M, Noshita N, Chan PH.  Brain Res Mol Brain Res.  2003; 113 (1-2): 28-36
• Cyclosporin A prevents calpain activation despite increased intracellular calcium concentrations, as well as translocation of apoptosis-inducing factor, cytochrome c and caspase-3 activation in neurons exposed to transient hypoglycemia. Ferrand-Drake M,  Zhu C, Gidö G, Hansen AJ, Karlsson JO, Bahr BA, Zamzami N, Kroemer G, Chan PH, Wieloch T, Blomgren K.  J Neurochem.  2003; 85 (6): 1431-42
• Treatment with dihydroethidium reduces infarct size after transient focal cerebral ischemia in mice. Yu F,  Sugawara T, Chan PH.  Brain Res.  2003; 978 (1-2): 223-7
• Induction of GRP78 by ischemic preconditioning reduces endoplasmic reticulum stress and prevents delayed neuronal cell death. Hayashi T,  Saito A, Okuno S, Ferrand-Drake M, Chan PH.  J Cereb Blood Flow Metab.  2003; 23 (8): 949-61
• Effects of cold injury-induced trauma in manganese superoxide dismutase-deficient mice. Grzeschik SM,  Maier CM, Chan PH.  J Neurotrauma.  2003; 20 (6): 571-81
• Interaction between XIAP and Smac/DIABLO in the mouse brain after transient focal cerebral ischemia. Saito A,  Hayashi T, Okuno S, Ferrand-Drake M, Chan PH.  J Cereb Blood Flow Metab.  2003; 23 (9): 1010-9
• Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption? Kim GW,  Gasche Y, Grzeschik S, Copin JC, Maier CM, Chan PH.  J Neurosci.  2003; 23 (25): 8733-42
• Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. Sugawara T,  Lewén A, Noshita N, Gasche Y, Chan PH.  J Neurotrauma.  2002; 19 (1): 85-98
• Manganese superoxide dismutase deficiency exacerbates cerebral infarction after focal cerebral ischemia/reperfusion in mice: implications for the production and role of superoxide radicals. Kim GW,  Kondo T, Noshita N, Chan PH.  Stroke.  2002; 33 (3): 809-15
• Akt phosphorylation and neuronal survival after traumatic brain injury in mice. Noshita N,  Lewén A, Sugawara T, Chan PH.  Neurobiol Dis.  2002; 9 (3): 294-304
• Carbohydrate source influences gelatinase production by mouse astrocytes in vitro. Massengale JL,  Gasche Y, Chan PH.  Glia.  2002; 38 (3): 240-5
• Involvement of superoxide in excitotoxicity and DNA fragmentation in striatal vulnerability in mice after treatment with the mitochondrial toxin, 3-nitropropionic acid. Kim GW,  Chan PH.  J Cereb Blood Flow Metab.  2002; 22 (7): 798-809
• Overexpression of copper/zinc superoxide dismutase in transgenic rats protects vulnerable neurons against ischemic damage by blocking the mitochondrial pathway of caspase activation. Sugawara T,  Noshita N, Lewén A, Gasche Y, Ferrand-Drake M, Fujimura M, Morita-Fujimura Y, Chan PH.  J Neurosci.  2002; 22 (1): 209-17
• Copper/zinc superoxide dismutase attenuates neuronal cell death by preventing extracellular signal-regulated kinase activation after transient focal cerebral ischemia in mice. Noshita N,  Sugawara T, Hayashi T, Lewén A, Omar G, Chan PH.  J Neurosci.  2002; 22 (18): 7923-30
• Overexpression of SOD1 protects vulnerable motor neurons after spinal cord injury by attenuating mitochondrial cytochrome c release. Sugawara T,  Lewén A, Gasche Y, Yu F, Chan PH.  FASEB J.  2002; 16 (14): 1997-9
• Effects of mild hypothermia on superoxide anion production, superoxide dismutase expression, and activity following transient focal cerebral ischemia. Maier CM,  Sun GH, Cheng D, Yenari MA, Chan PH, Steinberg GK.  Neurobiol Dis.  2002; 11 (1): 28-42
• Mild hypothermia attenuates cytochrome c release but does not alter Bcl-2 expression or caspase activation after experimental stroke. Yenari MA,  Iwayama S, Cheng D, Sun GH, Fujimura M, Morita-Fujimura Y, Chan PH, Steinberg GK.  J Cereb Blood Flow Metab.  2002; 22 (1): 29-38
• Role of superoxide dismutases in oxidative damage and neurodegenerative disorders. Maier CM,  Chan PH.  Neuroscientist.  2002; 8 (4): 323-34
• Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. Gasche Y,  Copin JC, Sugawara T, Fujimura M, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (12): 1393-400
• Evidence of phosphorylation of Akt and neuronal survival after transient focal cerebral ischemia in mice. Noshita N,  Lewén A, Sugawara T, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (12): 1442-50
• Delayed treatment with polynitroxyl albumin reduces infarct size after stroke in rats. Sugawara T,  Yu F, Ma L, Hsia CJ, Chan PH.  Neuroreport.  2001; 12 (16): 3609-12
• Reactive oxygen radicals in signaling and damage in the ischemic brain. Chan PH,  J Cereb Blood Flow Metab.  2001; 21 (1): 2-14
• Prolonged hypoxia during cell development protects mature manganese superoxide dismutase-deficient astrocytes from damage by oxidative stress. Copin JC,  Gasche Y, Li Y, Chan PH.  FASEB J.  2001; 15 (2): 525-34
• Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutase-deficient mice after exposure to subarachnoid hemolysate. Matz PG,  Fujimura M, Lewen A, Morita-Fujimura Y, Chan PH.  Stroke.  2001; 32 (2): 506-15
• Oxidative stress and neuronal DNA fragmentation mediate age-dependent vulnerability to the mitochondrial toxin, 3-nitropropionic acid, in the mouse striatum. Kim GW,  Chan PH.  Neurobiol Dis.  2001; 8 (1): 114-26
• Reduction of copper, zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia. Fujimura M,  Morita-Fujimura Y, Copin J, Yoshimoto T, Chan PH.  Brain Res.  2001; 889 (1-2): 208-13
• SOD1 down-regulates NF-kappaB and c-Myc expression in mice after transient focal cerebral ischemia. Huang CY,  Fujimura M, Noshita N, Chang YY, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (2): 163-73
• Overexpression of copper-zinc superoxide dismutase attenuates acute activation of activator protein-1 after transient focal cerebral ischemia in mice. Huang CY,  Fujimura M, Chang YY, Chan PH.  Stroke.  2001; 32 (3): 741-7
• Manganese Superoxide Dismutase Affects Cytochrome c Release and Caspase-9 Activation After Transient Focal Cerebral Ischemia in Mice. Noshita N,  Sugawara T, Fujimura M, Morita-Fujimura Y, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (5): 557-67
• Early decrease in dna repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Kim GW,  Noshita N, Sugawara T, Chan PH.  Stroke.  2001; 32 (6): 1401-7
• Oxidative cellular damage and the reduction of APE/Ref-1 expression after experimental traumatic brain injury. Lewén A,  Sugawara T, Gasche Y, Fujimura M, Chan PH.  Neurobiol Dis.  2001; 8 (3): 380-90
• Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury. Lewén A,  Fujimura M, Sugawara T, Matz P, Copin JC, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (8): 914-20
• Neuronal expression of the DNA repair protein Ku 70 after ischemic preconditioning corresponds to tolerance to global cerebral ischemia. Sugawara T,  Noshita N, Lewén A, Kim GW, Chan PH.  Stroke.  2001; 32 (10): 2388-93
• Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke. Morita-Fujimura Y,  Fujimura M, Yoshimoto T, Chan PH.  Stroke.  2001; 32 (10): 2356-61
• The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice. Kim GW,  Lewén A, Copin J, Watson BD, Chan PH.  Neuroscience.  2001; 105 (4): 1007-18
• Neuronal, but not microglial, accumulation of extravasated serum proteins after intracerebral hemolysate exposure is accompanied by cytochrome c release and DNA fragmentation. Matz PG,  Lewén A, Chan PH.  J Cereb Blood Flow Metab.  2001; 21 (8): 921-8
• Overexpression of copper/zinc superoxide dismutase does not prevent neonatal lethality in mutant mice that lack manganese superoxide dismutase. Copin JC,  Gasche Y, Chan PH.  Free Radic Biol Med.  2000; 28 (10): 1571-6
• Spreading depression-induced expression of c-fos and cyclooxygenase-2 in transgenic mice that overexpress human copper/zinc-superoxide dismutase. Yrjänheikki J,  Koistinaho J, Copin JC, de Crespigny A, Moseley ME, Chan PH.  J Neurotrauma.  2000; 17 (8): 713-8
• Effect of hypotension severity on hippocampal CA1 neurons in a rat global ischemia model. Sugawara T,  Kawase M, Lewén A, Noshita N, Gasche Y, Fujimura M, Chan PH.  Brain Res.  2000; 877 (2): 281-7
• Cell death after exposure to subarachnoid hemolysate correlates inversely with expression of CuZn-superoxide dismutase. Matz PG,  Copin JC, Chan PH.  Stroke.  2000; 31 (10): 2450-9
• Free radical pathways in CNS injury. Lewén A,  Matz P, Chan PH.  J Neurotrauma.  2000; 17 (10): 871-90
• Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Manley GT,  Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS.  Nat Med.  2000; 6 (2): 159-63
• Overexpression of copper and zinc superoxide dismutase in transgenic mice prevents the induction and activation of matrix metalloproteinases after cold injury-induced brain trauma. Morita-Fujimura Y,  Fujimura M, Gasche Y, Copin JC, Chan PH.  J Cereb Blood Flow Metab.  2000; 20 (1): 130-8
• The cytosolic antioxidant copper/zinc-superoxide dismutase prevents the early release of mitochondrial cytochrome c in ischemic brain after transient focal cerebral ischemia in mice. Fujimura M,  Morita-Fujimura Y, Noshita N, Sugawara T, Kawase M, Chan PH.  J Neurosci.  2000; 20 (8): 2817-24
• Subarachnoid hemolysate produces DNA fragmentation in a pattern similar to apoptosis in mouse brain. Matz PG,  Fujimura M, Chan PH.  Brain Res.  2000; 858 (2): 312-9
• Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice. Fujimura M,  Morita-Fujimura Y, Noshita N, Yoshimoto T, Chan PH.  Brain Res.  2000; 869 (1-2): 105-11
• Spreading depression-induced cyclooxygenase-2 expression in the cortex. Koistinaho J,  Chan PH.  Neurochem Res.  2000; 25 (5): 645-51
• Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice. Kim GW,  Sugawara T, Chan PH.  J Cereb Blood Flow Metab.  2000; 20 (12): 1690-701
• Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme. Chang YY,  Fujimura M, Morita-Fujimura Y, Kim GW, Huang CY, Wu HS, Kawase M, Copin JC, Chan PH.  Neurosci Lett.  1999; 277 (1): 61-4
• Mitochondrial release of cytochrome c corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. Sugawara T,  Fujimura M, Morita-Fujimura Y, Kawase M, Chan PH.  J Neurosci.  1999; 19 (22): RC39
• Reduction of apurinic/apyrimidinic endonuclease expression after transient global cerebral ischemia in rats: implication of the failure of DNA repair in neuronal apoptosis. Kawase M,  Fujimura M, Morita-Fujimura Y, Chan PH.  Stroke.  1999; 30 (2): 441-8; discussion 449
• A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Yrjänheikki J,  Tikka T, Keinänen R, Goldsteins G, Chan PH, Koistinaho J.  Proc Natl Acad Sci U S A.  1999; 96 (23): 13496-500
• Early decrease of XRCC1, a DNA base excision repair protein, may contribute to DNA fragmentation after transient focal cerebral ischemia in mice. Fujimura M,  Morita-Fujimura Y, Sugawara T, Chan PH.  Stroke.  1999; 30 (11): 2456-62; discussion 2463
• Copper-zinc superoxide dismutase prevents the early decrease of apurinic/apyrimidinic endonuclease and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Fujimura M,  Morita-Fujimura Y, Narasimhan P, Copin JC, Kawase M, Chan PH.  Stroke.  1999; 30 (11): 2408-15
• Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Fujimura M,  Gasche Y, Morita-Fujimura Y, Massengale J, Kawase M, Chan PH.  Brain Res.  1999; 842 (1): 92-100
• Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice. Morita-Fujimura Y,  Fujimura M, Kawase M, Chan PH.  Neuroscience.  1999; 93 (4): 1465-73
• Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. Gasche Y,  Fujimura M, Morita-Fujimura Y, Copin JC, Kawase M, Massengale J, Chan PH.  J Cereb Blood Flow Metab.  1999; 19 (9): 1020-8
• Exacerbation of delayed cell injury after transient global ischemia in mutant mice with CuZn superoxide dismutase deficiency. Kawase M,  Murakami K, Fujimura M, Morita-Fujimura Y, Gasche Y, Kondo T, Scott RW, Chan PH.  Stroke.  1999; 30 (9): 1962-8
• Release of mitochondrial cytochrome c and DNA fragmentation after cold injury-induced brain trauma in mice: possible role in neuronal apoptosis. Morita-Fujimura Y,  Fujimura M, Kawase M, Chen SF, Chan PH.  Neurosci Lett.  1999; 267 (3): 201-5
• Inhibition of interleukin-1beta converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice. Morita-Fujimura Y,  Fujimura M, Kawase M, Murakami K, Kim GW, Chan PH.  J Cereb Blood Flow Metab.  1999; 19 (6): 634-42
• Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice. Fujimura M,  Morita-Fujimura Y, Kawase M, Chan PH.  J Cereb Blood Flow Metab.  1999; 19 (5): 495-501
• Manganese superoxide dismutase mediates the early release of mitochondrial cytochrome C and subsequent DNA fragmentation after permanent focal cerebral ischemia in mice. Fujimura M,  Morita-Fujimura Y, Kawase M, Copin JC, Calagui B, Epstein CJ, Chan PH.  J Neurosci.  1999; 19 (9): 3414-22
• Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats. Fujimura M,  Morita-Fujimura Y, Murakami K, Kawase M, Chan PH.  J Cereb Blood Flow Metab.  1998; 18 (11): 1239-47
• Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion. Chan PH,  Kawase M, Murakami K, Chen SF, Li Y, Calagui B, Reola L, Carlson E, Epstein CJ.  J Neurosci.  1998; 18 (20): 8292-9