Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice.

Abstract:

:Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. Our previous studies have demonstrated that Fasudil, a selective ROCK inhibitor, induced neuroprotection in vitro. Here we used an in vivo model of hypoxia/reoxygenation (H/R) injury to examine the neuroprotective effect of Fasudil, and explore its possible mechanism(s) in vivo. H/R resulted in the loss of hippocampal neurons, accompanied by increased apoptosis of neurons in hippocampus. The expression of ROCK II and activity of ROCK in the brain were increased after H/R, and located only in microglia, but not in astrocytes and neurons. The administration of Fasudil inhibited the activity of ROCK in brain tissue and cultured microglia, and protected hippocampal neurons against H/R injury. Further immunohistochemical analysis and cytokine determination revealed that Fasudil inhibited inducible nitric oxide synthase immunoreactivity in microglia and pro-inflammatory factors in brain tissue after H/R, which is consistent with the observation wherein Fasudil reduced the pro-inflammatory factors nitric oxide, IL-1β, IL-6 and TNF-, and increased anti-inflammatory factor IL-10 in cultured microglia under normoxic or hypoxic conditions. Our results indicate that inhibition of ROCK by Fasudil may represent a useful therapeutic perspective by inhibiting microglial inflammatory responses in the CNS.

journal_name

J Neurochem

authors

Ding J,Li QY,Wang X,Sun CH,Lu CZ,Xiao BG

doi

10.1111/j.1471-4159.2010.06876.x

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

1619-29

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

114

pub_type

杂志文章
  • Multiple levels for regulation of TrkA in PC12 cells by nerve growth factor.

    abstract::TrkA is a receptor tyrosine kinase for nerve growth factor (NGF). Recent studies indicate that NGF regulates not only activation of trkA kinase but also expression of the trkA gene. To further define NGF actions on trkA, we examined binding and signaling through trkA after both short and long intervals of NGF treatmen...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.65031146.x

    authors: Zhou J,Valletta JS,Grimes ML,Mobley WC

    更新日期:1995-09-01 00:00:00

  • Transcriptional responses to growth factor and G protein-coupled receptors in PC12 cells: comparison of alpha(1)-adrenergic receptor subtypes.

    abstract::Transcriptional responses to growth factor and G protein-coupled receptors were compared in PC12 cells using retroviral luciferase reporters. In cells stably expressing alpha(1A)-adrenergic receptors, norepinephrine activated all five reporters [AP1 (activator protein-1), SRE (serum response element), CRE (cyclic AMP ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0742392.x

    authors: Minneman KP,Lee D,Zhong H,Berts A,Abbott KL,Murphy TJ

    更新日期:2000-06-01 00:00:00

  • Involvement of the AT1 receptor subtype in the effects of angiotensin IV and LVV-haemorphin 7 on hippocampal neurotransmitter levels and spatial working memory.

    abstract::Intracerebroventricular (i.c.v.) administration of angiotensin IV (Ang IV) or Leu-Val-Val-haemorphin 7 (LVV-H7) improves memory performance in normal rats and reverses memory deficits in rat models for cognitive impairment. These memory effects were believed to be mediated via the putative 'AT4 receptor'. However, thi...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2009.06547.x

    authors: De Bundel D,Demaegdt H,Lahoutte T,Caveliers V,Kersemans K,Ceulemans AG,Vauquelin G,Clinckers R,Vanderheyden P,Michotte Y,Smolders I

    更新日期:2010-03-01 00:00:00

  • Altered mitochondrial respiration in selectively vulnerable brain subregions following transient forebrain ischemia in the rat.

    abstract::Mitochondrial respiratory function, assessed from the rate of oxygen uptake by homogenates of rat brain subregions, was examined after 30 min of forebrain ischemia and at recirculation periods of up to 48 h. Ischemia-sensitive regions which develop extensive neuronal loss during the recirculation period (dorsal-latera...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1987.tb01001.x

    authors: Sims NR,Pulsinelli WA

    更新日期:1987-11-01 00:00:00

  • The synaptic vesicle proteome.

    abstract::Synaptic vesicles are key organelles in neurotransmission. Vesicle integral or membrane-associated proteins mediate the various functions the organelle fulfills during its life cycle. These include organelle transport, interaction with the nerve terminal cytoskeleton, uptake and storage of low molecular weight constit...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章,评审

    doi:10.1111/j.1471-4159.2007.04453.x

    authors: Burré J,Volknandt W

    更新日期:2007-06-01 00:00:00

  • Metallothionein-III prevents glutamate and nitric oxide neurotoxicity in primary cultures of cerebellar neurons.

    abstract::Metallothionein (MT)-III, a member of the MT family of metal-binding proteins, is mainly expressed in the CNS and is abundant in glutamatergic neurons. Results in genetically altered mice indicate that MT-III may play neuroprotective roles in the brain, but the mechanisms through which this protein functions have not ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2000.0750266.x

    authors: Montoliu C,Monfort P,Carrasco J,Palacios O,Capdevila M,Hidalgo J,Felipo V

    更新日期:2000-07-01 00:00:00

  • Superoxide dismutase, catalase, and glutathione peroxidase activities in copper/zinc-superoxide dismutase transgenic mice.

    abstract::Copper/zinc-superoxide dismutase (CuZn-SOD) transgenic mice overexpress the gene for human CuZn-SOD. To assess the effects of the overexpression of CuZn-SOD on the brain scavenging systems, we have measured the activities of manganese-SOD (Mn-SOD), catalase, and glutathione peroxidase (GSH-Px) in various regions of th...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1992.tb10051.x

    authors: Przedborski S,Jackson-Lewis V,Kostic V,Carlson E,Epstein CJ,Cadet JL

    更新日期:1992-05-01 00:00:00

  • Kernicterus: enzymatic evidence for difference between the development of cholinergic and GABAergic innervations in the brain of the Gunn rat.

    abstract::The activities of choline acetyltransferase (CAT) and glutamic acid decarboxylase (GAD), markers of cholinergic and GABAergic terminals, were measured in growing and adult Gunn rats, which possess an autosomal recessive gene for jaundice or kernicterus. In the olfactory tubercle, hippocampus, neostriatum, thalamus, an...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1981.tb04499.x

    authors: Ohno T

    更新日期:1981-10-01 00:00:00

  • Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice.

    abstract::Multiple molecular defects trigger cell death in amyotrophic lateral sclerosis (ALS). Among these, altered transcriptional activity may perturb many cellular functions, leading to a cascade of secondary pathological effects. We showed that pharmacological treatment, using the histone deacetylase inhibitor sodium pheny...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2005.03077.x

    authors: Ryu H,Smith K,Camelo SI,Carreras I,Lee J,Iglesias AH,Dangond F,Cormier KA,Cudkowicz ME,Brown RH Jr,Ferrante RJ

    更新日期:2005-06-01 00:00:00

  • Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

    abstract::Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor becaus...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.13977

    authors: Ohta KI,Suzuki S,Warita K,Kaji T,Kusaka T,Miki T

    更新日期:2017-04-01 00:00:00

  • Oxidized low density lipoproteins induce a pathologic response by retinal pigmented epithelial cells.

    abstract::The accumulation of apolipoprotein B100 lipoproteins in Bruch membrane is an early event thought to promote age-related macular degeneration (AMD). Immunohistochemistry using an anti-oxidized low density lipoprotein antibody on 10 AMD specimens showed staining in Bruch membrane including basal deposits, a marker of AM...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2008.05211.x

    authors: Yamada Y,Tian J,Yang Y,Cutler RG,Wu T,Telljohann RS,Mattson MP,Handa JT

    更新日期:2008-05-01 00:00:00

  • Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells.

    abstract::The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neurop...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2002.01224.x

    authors: Wang X,Qin ZH,Leng Y,Wang Y,Jin X,Chase TN,Bennett MC

    更新日期:2002-12-01 00:00:00

  • Excitatory and inhibitory effects of A1 and A2A adenosine receptor activation on the electrically evoked [3H]acetylcholine release from different areas of the rat hippocampus.

    abstract::The modulation by adenosine analogues and endogenous adenosine of the electrically evoked release of [3H]acetylcholine ([3H]ACh) was compared in subslices of the three areas of the rat hippocampus (CA1, CA3, and dentate gyrus). The mixed A1/A2 agonist 2-chloroadenosine (CADO; 2-10 microM) inhibited, in a concentration...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.63010207.x

    authors: Cunha RA,Milusheva E,Vizi ES,Ribeiro JA,Sebastião AM

    更新日期:1994-07-01 00:00:00

  • Blockade of neurotensin receptor by SR 48692 potentiates the facilitatory effect of haloperidol on the evoked in vivo dopamine release in the rat nucleus accumbens.

    abstract::The present experiments assessed the effects of SR 48692, a selective nonpeptide antagonist of neurotensin receptors, on mesolimbic dopaminergic neurotransmission. Dopamine release evoked by the electrical stimulation of the median forebrain bundle (20 Hz, 10 s) was measured in the nucleus accumbens of urethane-anesth...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1995.64052073.x

    authors: Brun P,Steinberg R,Le Fur G,Soubrié P

    更新日期:1995-05-01 00:00:00

  • Phospholipase A2 modulates different subtypes of excitatory amino acid receptors: autoradiographic evidence.

    abstract::Exogenous phospholipases have been used extensively as tools to study the role of membrane lipids in receptor mechanisms. We used in vitro quantitative autoradiography to evaluate the effect of phospholipase A2 (PLA2) on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in rat brain. PLA2 pretreatment induc...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1993.tb05843.x

    authors: Catania MV,Hollingsworth Z,Penney JB,Young AB

    更新日期:1993-01-01 00:00:00

  • Splice variation in the cytoplasmic domains of myelin oligodendrocyte glycoprotein affects its cellular localisation and transport.

    abstract::Although myelin oligodendrocyte glycoprotein is a candidate autoantigen in multiple sclerosis, its function remains unknown. In humans, mRNA expressed by the myelin oligodendrocyte glycoprotein gene is alternatively spliced resulting in at least nine unique protein isoforms. In this study, we investigated the sub-cell...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2007.04687.x

    authors: Boyle LH,Traherne JA,Plotnek G,Ward R,Trowsdale J

    更新日期:2007-09-01 00:00:00

  • Bradykinin induces interleukin-6 expression in astrocytes through activation of nuclear factor-kappaB.

    abstract::Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of the blood-brain barri...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1999.0731461.x

    authors: Schwaninger M,Sallmann S,Petersen N,Schneider A,Prinz S,Libermann TA,Spranger M

    更新日期:1999-10-01 00:00:00

  • Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal.

    abstract::Deposits of amyloid beta-peptide (A beta), reduced glucose uptake into brain cells, oxidative damage to cellular proteins and lipids, and excitotoxic mechanisms have all been suggested to play roles in the neurodegenerative process in Alzheimer's disease. Synapse loss is closely correlated with cognitive impairments i...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.69010273.x

    authors: Keller JN,Pang Z,Geddes JW,Begley JG,Germeyer A,Waeg G,Mattson MP

    更新日期:1997-07-01 00:00:00

  • Inhibitors of histamine methylation in brain promote formation of imidazoleacetic acid, which interacts with GABA receptors.

    abstract::In brain, the precursor of imidazoleacetic acid (IAA), a GABAA agonist but a GABAC antagonist, is not known. In the periphery, IAA derives from oxidation of histamine. But in brain, histamine is thought to be metabolized solely by histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele-methylim...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.68010142.x

    authors: Prell GD,Morrishow AM,Duoyon E,Lee WS

    更新日期:1997-01-01 00:00:00

  • Amino acid neurotransmitters in nucleus tractus solitarius: an in vivo microdialysis study.

    abstract::Amino acid neurotransmitters in the nucleus tractus solitarius (NTS) are thought to play a key role in the mediation of visceral reflexes and glutamate has been proposed as the neurotransmitter of visceral afferent nerves projecting to this region. The present studies sought to characterize the use of in vivo microdia...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1993.tb07446.x

    authors: Sved AF,Curtis JT

    更新日期:1993-12-01 00:00:00

  • Fingolimod confers neuroprotection through activation of Rac1 after experimental germinal matrix hemorrhage in rat pups.

    abstract::Fingolimod, a sphingosine-1-phosphate receptor (S1PR) agonist, is clinically available to treat multiple sclerosis and is showing promise in treating stroke. We investigated if fingolimod provides long-term protection from experimental neonatal germinal matrix hemorrhage (GMH), aiming to support a potential mechanism ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.13946

    authors: Rolland WB,Krafft PR,Lekic T,Klebe D,LeGrand J,Weldon AJ,Xu L,Zhang JH

    更新日期:2017-03-01 00:00:00

  • Modulation of serotonin transporter activity by a protein kinase C activator and an inhibitor of type 1 and 2A serine/threonine phosphatases.

    abstract::We studied the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C (PKC) activator, and calyculin A (CLA), an inhibitor of type 1 and 2A serine/threonine phosphatases, on serotonin uptake by a human placenta choriocarcinoma cell line (BeWo) and COS-7 cells expressing recombinant serotonin transpo...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1997.68062618.x

    authors: Sakai N,Sasaki K,Nakashita M,Honda S,Ikegaki N,Saito N

    更新日期:1997-06-01 00:00:00

  • Chronic ingestion of ethanol up-regulates NMDAR1 receptor subunit immunoreactivity in rat hippocampus.

    abstract::We examined the effects of chronic ethanol exposure on the levels of N-methyl-D-aspartate receptor subunit 1 (NMDAR1) protein, an essential component of N-methyl-D-aspartate glutamate receptors, in rat brain. By immunoblotting procedures using a specific antibody for the NMDAR1 subunit, we found that ethanol dramatica...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1994.62041635.x

    authors: Trevisan L,Fitzgerald LW,Brose N,Gasic GP,Heinemann SF,Duman RS,Nestler EJ

    更新日期:1994-04-01 00:00:00

  • The neuroprotective effect of latanoprost acts via klotho-mediated suppression of calpain activation after optic nerve transection.

    abstract::Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well-known that latanoprost exerts an ocular hypotensive eff...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/jnc.13902

    authors: Yamamoto K,Sato K,Yukita M,Yasuda M,Omodaka K,Ryu M,Fujita K,Nishiguchi KM,Machida S,Nakazawa T

    更新日期:2017-02-01 00:00:00

  • Peroxidative stress selectively down-regulates the neuronal stress response activated under conditions of endoplasmic reticulum dysfunction.

    abstract::Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Here, we investigated the effect of peroxide exposure on the expression of genes coding for cytoplasmic and endoplasmic reticulum (ER) stress proteins. Primary neuronal cell cultures were exp...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.2001.00206.x

    authors: Paschen W,Mengesdorf T,Althausen S,Hotop S

    更新日期:2001-03-01 00:00:00

  • Characterization of the striatal dopaminergic neurotransmission in MEN2B mice with elevated cerebral tissue dopamine.

    abstract::The Ret receptor tyrosine kinase is the common signaling receptor for the glial cell line-derived neurotrophic factor (GDNF) family ligands. The Met918Thr mutation leads to constitutive activation of Ret and is responsible for dominantly inherited cancer syndrome MEN2B. Previously, we found that the mice carrying the ...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2008.05265.x

    authors: Mijatovic J,Patrikainen O,Yavich L,Airavaara M,Ahtee L,Saarma M,Piepponen TP

    更新日期:2008-06-01 00:00:00

  • Kainic acid inhibits the synaptosomal plasma membrane glutamate carrier and allows glutamate leakage from the cytoplasm but does not affect glutamate exocytosis.

    abstract::Kainate inhibits the exchange of D-aspartate into guinea-pig cerebrocortical synaptosomes. Kainate inhibits the Ca2+-independent efflux of endogenous glutamate in the presence of a trapping system for the released amino acid but potentiates a Ca2+-independent net efflux of endogenous and labelled glutamate and asparta...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.1988.tb02977.x

    authors: Pocock JM,Murphie HM,Nicholls DG

    更新日期:1988-03-01 00:00:00

  • Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates the expression and the release of tissue plasminogen activator (tPA) in neuronal cells: involvement of tPA in the neuroprotective effect of PACAP.

    abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) and tissue plasminogen activator (tPA) play important roles in neuronal migration and survival. However, a direct link between the neurotrophic effects of PACAP and tPA has never been investigated. In this study, we show that, in PC12 cells, PACAP induced a 9....

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2011.07486.x

    authors: Raoult E,Roussel BD,Bénard M,Lefebvre T,Ravni A,Ali C,Vivien D,Komuro H,Fournier A,Vaudry H,Vaudry D,Galas L

    更新日期:2011-12-01 00:00:00

  • Immunohistochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17alpha-hydroxylase/C17, 20-lyase (P450C17) in the frog brain and pituitary.

    abstract::It is now clearly established that the brain has the capability of synthesizing various biologically active steroids including 17-hydroxypregnenolone (17OH-Delta(5)P), 17-hydroxyprogesterone (17OH-P), dehydroepiandrosterone (DHEA) and androstenedione (Delta(4)). However, the presence, distribution and activity of cyto...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1111/j.1471-4159.2006.04209.x

    authors: Do Rego JL,Tremblay Y,Luu-The V,Repetto E,Castel H,Vallarino M,Bélanger A,Pelletier G,Vaudry H

    更新日期:2007-01-01 00:00:00

  • Identification and characterization of the rat M1 muscarinic receptor promoter.

    abstract::Five subtypes of the muscarinic receptor have been cloned from both the rat and human genomes. Although all five genes have the coding sequences in a single exon, their structures 5' of the initiation codon are largely uncharacterized, except for the M4 receptor. In the brain, muscarinic receptors mediate motor and me...

    journal_title:Journal of neurochemistry

    pub_type: 杂志文章

    doi:10.1046/j.1471-4159.1999.0720900.x

    authors: Klett CP,Bonner TI

    更新日期:1999-03-01 00:00:00