Molecular targets in cerebral ischemia for developing novel therapeutics

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Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes

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Stroke Trends in the WHO MONICA Project

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Therapeutic neutralization of CD95-ligand and TNF attenuates brain damage in stroke

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An ICE inhibitor, z-VAD-DCB attenuates ischaemic brain damage in the rat

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Peripheral Administration of Interleukin-1 Receptor Antagonist Inhibits Brain Damage after Focal Cerebral Ischemia in the Rat

1996 • 206 citations

JNK-dependent Release of Mitochondrial Protein, Smac, during Apoptosis in Multiple Myeloma (MM) Cells

2003 • 206 citations

Evolution of Brain Infarction after Transient Focal Cerebral Ischemia in Mice

2000 • 205 citations

Attenuation of Ischemia-Induced Cellular and Behavioral Deficits by X Chromosome-Linked Inhibitor of Apoptosis Protein Overexpression in the Rat Hippocampus

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Periinfarct depolarizations.

1996 • 202 citations

Diablo Promotes Apoptosis by Removing Miha/Xiap from Processed Caspase 9

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Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain

1994 • 197 citations

Astrocytic Gap Junctions Composed of Connexin 43 Reduce Apoptotic Neuronal Damage in Cerebral Ischemia

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Fundamental role of the Rip2/caspase-1 pathway in hypoxia and ischemia-induced neuronal cell death

2003 • 195 citations

Serial Analysis of Gene Expression Identifies Metallothionein-II as Major Neuroprotective Gene in Mouse Focal Cerebral Ischemia

2002 • 191 citations

Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke

2006 • 191 citations

Apoptotic and Necrotic Death Mechanisms Are Concomitantly Activated in the Same Cell After Cerebral Ischemia

2004 • 191 citations

Targeting of C‐Terminal (Tail)‐Anchored Proteins: Understanding how Cytoplasmic Activities are Anchored to Intracellular Membranes

2001 • 190 citations

Hsp70 Overexpression Sequesters AIF and Reduces Neonatal Hypoxic/Ischemic Brain Injury

2005 • 189 citations

CREB Phosphorylation Promotes Nerve Cell Survival

1999 • 189 citations

Antibodies against Adhesion Molecules Reduce Apoptosis after Transient Middle Cerebral Artery Occlusion in Rat Brain

1996 • 188 citations

Intercellular adhesion molecule‐1‐deficient mice are less susceptible to cerebral ischemia‐reperfusion lnjury

1996 • 183 citations

Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons

2006 • 182 citations

Cross-talk between JNK/SAPK and ERK/MAPK Pathways

2003 • 182 citations

Expression of Interleukin-6, c-Fos, and zif268 mRNAs in Rat Ischemic Cortex

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The crystal structure of the mouse apoptosis-inducing factor AIF

2002 • 178 citations

Boo, a novel negative regulator of cell death, interacts with Apaf-1

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Astrocytes and Stroke: Networking for Survival?

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Neuroprotection in Transient Focal Brain Ischemia After Delayed Intravenous Administration of Brain-Derived Neurotrophic Factor Conjugated to a Blood-Brain Barrier Drug Targeting System

2001 • 172 citations

Intravenous TAT-GDNF Is Protective After Focal Cerebral Ischemia in Mice

2003 • 167 citations

Nuclear Translocation of Apoptosis-Inducing Factor after Focal Cerebral Ischemia

2004 • 167 citations

Synergistic effects of caspase inhibitors and MK‐801 in brain injury after transient focal cerebral ischaemia in mice

1998 • 166 citations

Apoptosis Induced by p75NTR Overexpression Requires Jun Kinase-Dependent Phosphorylation of Bad

2003 • 164 citations

Transient Global Forebrain Ischemia Induces a Prolonged Expression of the Caspase-3 mRNA in Rat Hippocampal CA1 Pyramidal Neurons

1998 • 164 citations

ARL 17477, a Potent and Selective Neuronal NOS Inhibitor Decreases Infarct Volume after Transient Middle Cerebral Artery Occlusion in Rats

1996 • 163 citations

The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B.

1995 • 162 citations

Ischemia‐induced programmed cell death in astrocytes

2005 • 158 citations

Molecular Cloning of a Novel Polypeptide, DP5, Induced during Programmed Neuronal Death

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Post-treatment with an inhibitor of poly(ADP-ribose) polymerase attenuates cerebral damage in focal ischemia

1999 • 155 citations

S-Nitrosoglutathione Reduces Inflammation and Protects Brain against Focal Cerebral Ischemia in a Rat Model of Experimental Stroke

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Activation of Mitogen‐Activated Protein Kinase in Cultured Rat Hippocampal Neurons by Stimulation of Glutamate Receptors

1995 • 155 citations

Neuroprotective effects of TNF binding protein in focal cerebral ischemia

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Nuclear Poly(ADP-ribose) Polymerase-1 Rapidly Triggers Mitochondrial Dysfunction

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Differential Regulation of Bax, Bcl‐2, and Bcl‐X Proteins in Focal Cortical Ischemia in the Rat

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Calcium/calmodulin‐dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons

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Estrogen and Stroke

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Which Targets Are Relevant for Therapy of Acute Ischemic Stroke?

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The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways

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RIP4 (DIK/PKK), a novel member of the RIP kinase family, activates NF‐κB and is processed during apoptosis

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Herpes Simplex Viral Vectors Expressing Bcl-2 Are Neuroprotective When Delivered After a Stroke

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Protective effects of melatonin in ischemic brain injury

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Mtd, a Novel Bcl-2 Family Member Activates Apoptosis in the Absence of Heterodimerization with Bcl-2 and Bcl-XL

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Poly(ADP-Ribose) Polymerase Impairs Early and Long-Term Experimental Stroke Recovery

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Administration of Melatonin After Onset of Ischemia Reduces the Volume of Cerebral Infarction in a Rat Middle Cerebral Artery Occlusion Stroke Model

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Parallel Gene Expression Monitoring using Oligonucleotide Probe Arrays of Multiple Transcripts with an Animal Model of Focal Ischemia

2000 • 122 citations

Mechanisms of Neuronal Damage in Brain Hypoxia/Ischemia

1998 • 122 citations

Distinct hsp70 Domains Mediate Apoptosis-inducing Factor Release and Nuclear Accumulation

2006 • 119 citations

The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair

1996 • 119 citations

Inhibition of Intercellular Adhesion Molecule-1 Protein Expression by Antisense Oligonucleotides Is Neuroprotective After Transient Middle Cerebral Artery Occlusion in Rat

2003 • 119 citations

Sex differences in cell death

2005 • 117 citations

Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice

2003 • 116 citations

Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia

2003 • 116 citations

Kallikrein Gene Transfer Protects Against Ischemic Stroke by Promoting Glial Cell Migration and Inhibiting Apoptosis

2003 • 115 citations

Death-associated Protein Kinase Is Activated by Dephosphorylation in Response to Cerebral Ischemia

2005 • 114 citations

Blk, a BH3-containing Mouse Protein That Interacts with Bcl-2 and Bcl-xL, Is a Potent Death Agonist

1998 • 113 citations

Effect of melatonin on ischemia reperfusion injury induced by middle cerebral artery occlusion in rats

2001 • 111 citations

Pretreatment with melatonin reduces volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model

2002 • 110 citations

An Inhibitor of p38 and JNK MAP Kinases Prevents Activation of Caspase and Apoptosis of Cultured Cerebellar Granule Neurons

1999 • 110 citations

Bid-mediated Mitochondrial Pathway Is Critical to Ischemic Neuronal Apoptosis and Focal Cerebral Ischemia

2002 • 109 citations

Ultrastructural morphological changes are not characteristic of apoptotic cell death following focal cerebral ischaemia in the rat

1996 • 105 citations

Neuroprotection for Acute Stroke

1999 • 104 citations

The DAP kinase family of pro‐apoptotic proteins: novel players in the apoptotic game

2001 • 103 citations

A caspase inhibitor blocks ischaemia‐induced delayed neuronal death in the gerbil

1998 • 100 citations

Persistent phosphorylation of cyclic amp responsive element-binding protein and activating transcription factor-2 transcription factors following transient cerebral ischemia in rat brain

1999 • 100 citations

Delayed effect of administration of COX-2 inhibitor in mice with acute cerebral ischemia

2003 • 99 citations

Manganese Superoxide Dismutase Affects Cytochrome c Release and Caspase-9 Activation after Transient Focal Cerebral Ischemia in Mice

2001 • 99 citations

Matrix metalloproteinase inhibitor KB-R7785 attenuates brain damage resulting from permanent focal cerebral ischemia in mice

2001 • 99 citations

TAT-mediated delivery of Bcl-xL protein is neuroprotective against neonatal hypoxic–ischemic brain injury via inhibition of caspases and AIF

2005 • 98 citations

Cleavage of DNA to Large Kilobase Pair Fragments Occurs in Some Forms of Necrosis as Well as Apoptosis

1995 • 98 citations

Bcl-2 Transfection via Herpes Simplex Virus Blocks Apoptosis-Inducing Factor Translocation after Focal Ischemia in the Rat

2004 • 95 citations

Apoptosis in cerebral ischemia: executional and regulatory signaling mechanisms

2004 • 94 citations

Further Evolution Toward Effective Therapy for Acute Ischemic Stroke

1998 • 91 citations

Caspase mRNA expression in a rat model of focal cerebral ischemia

2001 • 90 citations

Gene Expression Induced by Cerebral Ischemia

1997 • 89 citations

Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia

2003 • 89 citations

Stroke Genomics: Approaches to Identify, Validate, and Understand Ischemic Stroke Gene Expression

2001 • 89 citations

Cloning and Characterization of Rat Caspase-9: Implications for a Role in Mediating Caspase-3 Activation and Hippocampal Cell Death after Transient Cerebral Ischemia

2002 • 88 citations

Synthesis and release of interleukin 1 by reoxygenated human mononuclear phagocytes.

1992 • 88 citations

Xanthine oxidase-derived superoxide causes reoxygenation injury of ischemic cerebral endothelial cells

1998 • 86 citations

Serum levels of intercellular adhesion molecule-1 and E-selectin in patients with acute ischaemic stroke

1997 • 83 citations

Adeno-associated virus vector-mediated bcl-2 gene transfer into post-ischemic gerbil brain in vivo: prospects for gene therapy of ischemia-induced neuronal death

2000 • 82 citations

Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct

2001 • 81 citations

A Novel and Potent Poly(ADP-Ribose) Polymerase-1 Inhibitor, FR247304 (5-Chloro-2-[3-(4-phenyl-3,6-dihydro-1(2H)-pyridinyl)propyl]-4(3H)-quinazolinone), Attenuates Neuronal Damage in in Vitro and in Vivo Models of Cerebral Ischemia

2004 • 80 citations

Cerebral Endothelial Cell Apoptosis after Ischemia—Reperfusion: Role of PARP Activation and AIF Translocation

2005 • 80 citations

HuEP5C7 as a Humanized Monoclonal Anti-E/P-Selectin Neurovascular Protective Strategy in a Blinded Placebo-Controlled Trial of Nonhuman Primate Stroke

2002 • 78 citations

Wide therapeutic time window for nimesulide neuroprotection in a model of transient focal cerebral ischemia in the rat

2004 • 77 citations

Targeting the central nervous system inflammatory response in ischemic stroke

2001 • 75 citations

Calcium Ion Transients in Peri-Infarct Depolarizations May Deteriorate Ion Homeostasis and Expand Infarction in Focal Cerebral Ischemia in Cats

2001 • 74 citations

Spatial resolution of phospholipid scramblase 1 (PLSCR1), caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia

2003 • 74 citations

Three-dimensional structures of proteins involved in programmed cell death

1997 • 72 citations

Interaction between XIAP and Smac/DIABLO in the Mouse Brain after Transient Focal Cerebral Ischemia

2003 • 70 citations

A single amino acid residue determines the Ca2+ permeability of AMPA-selective glutamate receptor channels

1991 • 68 citations

Murine models define the role of TGF-β as a master regulator of immune cell function

2000 • 68 citations

Long-term neuroprotective effect of inhibiting poly(ADP-ribose) polymerase in rats with middle cerebral artery occlusion using a behavioral assessment

2001 • 68 citations

Poly(ADP-ribose) polymerase inhibition protect neurons and the white matter and regulates the translocation of apoptosis-inducing factor in stroke

2004 • 67 citations

Fas (CD95) May Mediate Delayed Cell Death in Hippocampal CA1 Sector after Global Cerebral Ischemia

2001 • 67 citations

HSV amplicon delivery of glial cell line-derived neurotrophic factor is neuroprotective against ischemic injury

2003 • 66 citations

Recombinant Adeno-Associated Virus Vector Expressing Glial Cell Line-Derived Neurotrophic Factor Reduces Ischemia-Induced Damage

2000 • 66 citations

Astrocytic Function Assessed from 1-¹⁴C-Acetate Metabolism after Temporary Focal Cerebral Ischemia in Rats

2005 • 64 citations

Attenuation of Ischemia-Induced Mouse Brain Injury by SAG, a Redox-Inducible Antioxidant Protein

2001 • 63 citations

Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model

2002 • 62 citations

Transduced Tat-SOD Fusion Protein Protects Against Ischemic Brain Injury

2005 • 62 citations

Developmental changes in distribution of death-associated protein kinase mRNAs

1999 • 62 citations

Structure and regulation of calcium/calmodulin-dependent protein kinases II and IV

1996 • 61 citations

Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat

2003 • 60 citations

The neuroprotective effects of K252a through inhibiting MLK3/MKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region

2005 • 58 citations

A Newly Synthesized Poly(ADP-Ribose) Polymerase Inhibitor, DR2313 [2-Methyl-3,5,7,8-tetrahydrothiopyrano[4,3-d]-pyrimidine-4-one]: Pharmacological Profiles, Neuroprotective Effects, and Therapeutic Time Window in Cerebral Ischemia in Rats

2004 • 56 citations

Activation of mitogen-activated protein kinases in experimental cerebral ischemia

2002 • 56 citations

Effects of the cyclooxygenase-2 inhibitor nimesulide on cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion in the rat.

2005 • 55 citations

Poly (ADP-Ribose) Polymerase Inhibitors as Potential Therapeutic Agents in Stroke and Neurotrauma

2005 • 55 citations

Neuroprotective Effects of Virally Delivered HSPs in Experimental Stroke

2005 • 55 citations

Attenuation of a delayed increase in the extracellular glutamate level in the peri-infarct area following focal cerebral ischemia by a novel agent ONO-2506

2004 • 54 citations

Caspase-9 inhibition after focal cerebral ischemia improves outcome following reversible focal ischemia.

2002 • 54 citations

Global Forebrain Ischemia Induces a Posttranslational Modification of Multifunctional Calcium‐ and Calmodulin‐Dependent Kinase II

1992 • 54 citations

DNA array reveals altered gene expression in response to focal cerebral ischemia

2002 • 54 citations

Combination of Isoflurane and Caspase Inhibition Reduces Cerebral Injury in Rats Subjected to Focal Cerebral Ischemia

2004 • 52 citations

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

2003 • 50 citations

Treatment of Focal Cerebral Ischemia With Synthetic Oligopeptide Corresponding to Lectin Domain of Selectin

1996 • 49 citations

DAPK catalytic activity in the hippocampus increases during the recovery phase in an animal model of brain hypoxic-ischemic injury

2002 • 49 citations

Association of interleukin-1 alpha gene polymorphism with cerebral infarction

2003 • 49 citations

Sequence as well as functional similarity for DIABLO/Smac and Grim, Reaper and Hid?

2000 • 47 citations

The Mechanism of Conversion of Xanthine Dehydrogenase to Oxidase and the Role of the Enzyme in Reperfusion Injury

1991 • 47 citations

Activation of mitogen-activated protein kinases in gerbil hippocampus with ischemic tolerance induced by 3-nitropropionic acid

2000 • 45 citations

Regulation of XIAP and Smac/DIABLO in the rat hippocampus following transient forebrain ischemia

2004 • 44 citations

The Calmodulin Antagonist Trifluoperazine in Transient Focal Brain Ischemia in Rats

1997 • 44 citations

A neuroprotective role of extracellular signal-regulated kinase in n-acetyl-o-methyldopamine-treated hippocampal neurons after exposure to in vitro and in vivo ischemia

2003 • 44 citations

Recruitment of Several Neuroprotective Pathways after Permanent Focal Ischemia in Mice

1998 • 44 citations

Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia

2005 • 43 citations

Edaravone Inhibits JNK-c-Jun Pathway and Restores Anti-oxidative Defense after Ischemia-Reperfusion Injury in Aged Rats

2006 • 42 citations

Neuroprotective effect of 4-amino-1,8-napthalimide, a poly(ADP ribose) polymerase inhibitor in middle cerebral artery occlusion-induced focal cerebral ischemia in rat

2003 • 41 citations

Increased expression of adhesion molecule CD18 (LFA-1β) on the leukocytes of peripheral blood in patients with acute ischemic stroke

2009 • 41 citations

Temporal and topographic profiles of cyclooxygenase-2 expression during 24 h of focal brain ischemia in rats

2004 • 41 citations

Neuroprotective Effect of Melatonin on Brain Damage Induced by Acute Global Cerebral Ischemia in Cats

2001 • 40 citations

Function of BID – a Molecule of the bcl-2 Family – in Ischemic Cell Death in the Brain

2002 • 37 citations

An introduction to the changes in gene expression that occur after cerebral ischaemia

2000 • 36 citations

Altered Bad localization and interaction between Bad and Bcl-xL in the hippocampus after transient global ischemia

2004 • 33 citations

Effect of Cerebral Ischemia on Calcium/Calmodulin-Dependent Protein Kinase II Activity and Phosphorylation

1995 • 32 citations

Peri-Infarct Depolarizations Reveal Penumbra-Like Conditions in Striatum

2005 • 32 citations

Activation of Arc gene, a dendritic immediate early gene, by middle cerebral artery occlusion in rat brain

1999 • 31 citations

Autophosphorylated calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) reversibly targets to and phosphorylates N-methyl-d-aspartate receptor subunit 2B (NR2B) in cerebral ischemia and reperfusion in hippocampus of rats

2003 • 30 citations

Brain ischemia/reperfusion-induced expression of DP5 and its interaction with Bcl-2, thus freeing Bax from Bcl-2/Bax dimmers are mediated by c-Jun N-terminal kinase (JNK) pathway

2005 • 29 citations

Functional Proteins Involved in Regulation of Intracellular Ca2+ for Drug Development: Role of Calcium/Calmodulin-Dependent Protein Kinases in Ischemic Neuronal Death

2005 • 28 citations

Death associated protein kinase as a potential therapeutic target

2002 • 28 citations

Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1

2004 • 28 citations

Correlation between neuronal injury and Caspase-3 after focal ischemia in human hippocampus.

2004 • 26 citations

Deletion of the Kinase Domain in Death-Associated Protein Kinase Attenuates Tubular Cell Apoptosis in Renal Ischemia-Reperfusion Injury

2004 • 26 citations

Sendai Virus Vector-mediated Gene Transfer of Glial Cell Line-Derived Neurotrophic Factor Prevents Delayed Neuronal Death after Transient Global Ischemia in Gerbils.

2003 • 25 citations

Adenovirus-Mediated Bcl-XL Expression Using a Neuron-Specific Synapsin-1 Promoter Protects against Disseminated Neuronal Injury and Brain Infarction Following Focal Cerebral Ischemia in Mice

2002 • 25 citations

Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95 (PSD-95)/disc large/zonula occludens-1 (PDZ) domain of PSD-95

2004 • 25 citations

Post-ischemic administration of DY-9760e, a novel calmodulin antagonist, reduced infarct volume in the permanent focal ischemia model of spontaneously hypertensive rat

2001 • 23 citations

Serum factors and v-src control two complementary mitogenic pathways in quail neuroretinal cells in culture.

1993 • 22 citations

Effects of delayed intrathecal infusion of an NMDA receptor antagonist on ischemic injury and peri-infarct depolarizations

2005 • 20 citations

Correlation between neuronal injury and caspase-3 after focal ischemia in human hippocampus

2004 • 17 citations

Cerebrovascular diseases: pathophysiology, diagnosis, and treatment

1958 • 17 citations

Targeting PDZ Domain Proteins for Treating NMDA Receptor-Mediated Excitotoxicity

2006 • 17 citations

Transient cerebral ischemia decreases calcium/ calmodulin-dependent protein kinase II immunoreactivity, but not mRNA levels in the gerbil hippocampus

1995 • 14 citations

Brain ischemia as a potential target of gene therapy

2003 • 14 citations

ACUTE ISCHEMIC STROKE THERAPY

2000 • 14 citations

Cerebral ischemia immediately increases serine phosphorylation of the synaptic RAS-GTPase activating protein SynGAP by calcium/calmodulin-dependent protein kinase II α in hippocampus of rats

2003 • 12 citations

Does gene therapy become pharmacotherapy?

2005 • 12 citations

Calcium/calmodulin-dependent protein kinase II (CaMKII), through NMDA receptors and L-Voltage-gated channels, modulates the serine phosphorylation of GluR6 during cerebral ischemia and early reperfusion period in rat hippocampus

2005 • 12 citations

Evidence for crucial electrostatic interactions between Bcl-2 homology domains BH3 and BH4 in the anti-apoptotic Nr-13 protein

2002 • 11 citations

Deleted Work

1955 • 0 citations