Abstract:
:Stroke is the third leading cause of death in the US, with a prevalence of 750,000 patients per year, and a social cost estimated at $50 billion. Current therapeutics are targeted at restoring blood flow rather than on preventing the actual mechanisms associated with neuronal cell death. Here, we show that, following transient (2 h) middle cerebral artery occlusion (tMCAO) in male, Wistar rats, neuronal damage determined using MAP-2 staining increased progressively after the tMCAO. Notably, such neuronal degeneration was first associated with a decrease in p-Akt in both the focus and penumbra of the infarct region and, later with an increase in cytosolic cytochrome C levels in cortical neurons in the infarct area. These findings implicate that Akt alterations and consequent release of cytochrome C are involved in neuronal death. To further address this issue, NXY-059 (disodium 4-[(tert.-butylimino)methyl]benzene-1,3-disulfonate N-oxide) administered i.v. (30 mg/kg bolus, followed by 30 mg/kg/h infusion for up to 24 h), commencing 1 h after reperfusion, not only prevented the increase in infarct area but also attenuated the postreperfusion increase in neuronal cytosolic cytochrome C and the postperfusion decrease in neuronal p-Akt. Thus, NXY-059, by preventing mitochondrial cytochrome C release by maintaining activation of the Akt pathway, appears to protect neurons from damage after ischemia.
journal_name
Brain Resjournal_title
Brain researchauthors
Yoshimoto T,Kanakaraj P,Ying Ma J,Cheng M,Kerr I,Malaiyandi L,Watson JA,Siesjö BK,Maples KRdoi
10.1016/s0006-8993(02)02922-0subject
Has Abstractpub_date
2002-08-30 00:00:00pages
191-8issue
2eissn
0006-8993issn
1872-6240pii
S0006899302029220journal_volume
947pub_type
杂志文章相关文献
BRAIN RESEARCH文献大全abstract::Oxidative stress plays an important role in the pathogenesis of neurodegeneration after the acute central nervous system injury. We reported previously that increased nitric oxide (NO) production following spinal cord hemisection tends to lead to neurodegeneration in neurons of the nucleus dorsalis (ND) that normally ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2005.07.003
更新日期:2005-09-07 00:00:00
abstract::It is now well known that dopamine (DA) receptors agonists can reduce striatal DA release. These compounds are generally thought to produce short-term effects. However, in a recent in vivo study we have reported that the D1/D2 receptor agonist apomorphine might induce decrements in striatal DA release that lasted seve...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(94)90922-9
更新日期:1994-04-11 00:00:00
abstract::Reduced glutathione (GSH) plays an important role in cellular protection against damage from free radicals and other electrophiles. GSH in the rat central nervous system was quantitatively analyzed. In adult brain, tissue from the cerebellum and cerebrum had higher GSH levels than that from the brainstem and spinal co...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(90)90178-e
更新日期:1990-03-19 00:00:00
abstract::The fine structure of reaggregating cultures of cells from 6- to 7-day-old mouse cerebellum was studied at intervals between 3 and 21 days in vitro (DIV). The resulting aggregates consisted mainly of small neurons (granule, stellate and basket cells), neuroglial cells and their processes. Large neurons were rarely pre...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0165-3806(84)90067-1
更新日期:1984-09-01 00:00:00
abstract::Thermoregulation is a complex intercommunicative function requiring coordination between core body temperature (CBT), the central nervous system, and peripheral vasculature. In menopausal women, dysregulation of thermoregulatory mechanisms leads to hot flushes and night sweats. A previous study in ovariectomized (OVX)...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2006.09.050
更新日期:2006-12-06 00:00:00
abstract::Myelin of several Caudata (Urodela) species appears to be unique in the fact that it lacks hydroxycerebrosides and hydroxysulfatides although it contains their non-hydroxy counterparts. Comparison of the nerve conduction velocities in the Urodeles Necturus (salamander) and Notophthalmus (newt) with that in a reptile, ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(85)90831-5
更新日期:1985-10-14 00:00:00
abstract::Perineal muscles essential for copulatory functioning are innervated by Onuf's nucleus in humans and the spinal nucleus of the bulbocavernosus (SNB) and dorsolateral nucleus (DLN) in rats. These structures sexually differentiate as a result of developmental androgen exposure in most species examined. The homologous st...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2010.05.056
更新日期:2010-07-30 00:00:00
abstract::Neurokinins, such as substance P (SP), modulate the reflex regulation of cardiovascular and respiratory function in the CNS, particularly in the nucleus tractus solitarius (NTS). There is considerable evidence of the action of SP in the NTS, but the precise effects have not yet been determined. Voltage-dependent Ca2+ ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2006.06.060
更新日期:2006-09-19 00:00:00
abstract::Spontaneous hippocampal EEG activity and evoked field potentials were investigated in intact rats and in animals with fetal hippocampal grafts. Pieces of hippocampal grafts, derived from 15- to 16-day-old fetuses, were used to prepare cell suspensions and grafted directly into the intact hippocampus. Control animals r...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(91)90168-u
更新日期:1991-07-19 00:00:00
abstract::The immunosuppressive macrolide FK-506 has been shown to protect neurons in culture against glutamate excitotoxicity. This effect was attributed to the binding of immunosuppressants to calcineurin-inhibiting immunophilins. We now report that also the non-immunosuppressive macrolide antibiotics protect neurons in cultu...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(93)90098-8
更新日期:1993-10-08 00:00:00
abstract::The blood-brain barrier (BBB) restricts solute permeability across healthy cerebral endothelial cells. However, during inflammation, permeability is increased and can lead to deleterious cerebral edema. Neutrophils are early cellular participants in acute inflammation, but their effect on BBB permeability is unclear. ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2009.08.076
更新日期:2009-11-17 00:00:00
abstract::Commissural and ipsilateral intrinsic connections of the vestibular nuclear complex of cats were investigated using retrograde transport of horseradish peroxidase (HRP). HRP was microiontophoretically injected into limited areas (0.2-0.5 mm in diameter) of the respective vestibular nuclei. In the commissural connectio...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(85)91474-x
更新日期:1985-08-19 00:00:00
abstract::In view of the inconclusive findings relating the nuclei of the mammillary bodies (MB) with spatial memory, we evaluated the oxidative metabolic activity of the medial and lateral nuclei of the mammillary bodies (MB) after training young rats (30 days) of both sexes in the Morris water maze. Different groups were trai...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2004.03.025
更新日期:2004-06-11 00:00:00
abstract::The interaction of glutamatergic and dopamine neurotransmission is thought to have relevance to both the pathophysiology and pharmacotherapy of schizophrenia. For example, subanesthetic doses of the N-methyl-D-aspartate receptor (NMDA-R) antagonist ketamine induce schizophrenia-like behavioral effects in humans and bo...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(01)01991-6
更新日期:2001-03-16 00:00:00
abstract::Research supports the effectiveness of acupuncture for conditions such as chronic low back and knee pain. In a five-patient pilot study the modality also improved the symptoms of chemotherapy-induced neuropathic pain. Using an established rat model of paclitaxel-induced peripheral neuropathy, we evaluated the effect o...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2011.08.004
更新日期:2011-09-26 00:00:00
abstract::Nitric oxide (NO) is a neuronal messenger that it is thought to be involved in the nociceptive transmission modulation. The activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) was shown to be identical to NOS activity in the brain. Since the periaqueductal gray matter (PAG) plays an important ...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(98)00255-8
更新日期:1998-05-18 00:00:00
abstract::The present study examined if olfactory bulbectomy (OBX) altered defensive behaviors on the elevated plus-maze and the open-field differently in male and female rats. Similar increases in defensive behaviors in male and female rats were observed in both tests following OBX. No significant correlations were detected be...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(01)02421-0
更新日期:2001-06-08 00:00:00
abstract::Depending on experimental conditions, chronic cocaine exposure can induce an increase in binding to the dopamine transporter (DAT). One possible mechanism for the cocaine-induced-upregulation in DAT binding sites is through stimulation of presynaptic D2 receptors by excess synaptic dopamine. To test this hypothesis, t...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(96)01033-5
更新日期:1996-12-02 00:00:00
abstract::When N-methyl-D,L-aspartic acid was injected into the A5 catecholamine cell group of the rat, a dose-dependent decrease in blood pressure and heart rate was obtained. These cardiovascular changes were subsequently blocked by the (-) and (+) isomers of the aspartate receptor blocker 2-amino-5-phosphonovalerate (2-amino...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(82)90076-2
更新日期:1982-10-14 00:00:00
abstract::The effects of hypothermia on caspase-3 activation were investigated in the newborn rat brain after hypoxia-ischemia (HI). Intense caspase-3 activation was observed in the control brains after HI, but this activation was significantly reduced by postischemic hypothermia. These findings suggest that the inhibition of c...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(01)02659-2
更新日期:2001-08-10 00:00:00
abstract::Rats were subjected to transient global ischemia (four vessel occlusion) and time-related changes in the selectively vulnerable hippocampal field CA1 were characterized. The assessment included ex vivo field responses to afferent stimulation, silver staining, calpain-induced spectrin breakdown, chromatolysis, and cell...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(97)01414-5
更新日期:1998-04-20 00:00:00
abstract::The projections of serotonin-containing neurons of the midbrain raphe nuclei (nucleus raphe dorsalis, nucleus centralis superior) are studied by analysis of axonal transport of labeled amino acids. These results are correlated with regional alterations of serotonin content following midbrain raphe lesions which produc...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(76)90144-x
更新日期:1976-05-14 00:00:00
abstract::To achieve a better understanding of the parallel information processing that takes place in the nervous system, many researchers have recently begun to use multielectrode techniques to obtain high spatial- and temporal-resolution recordings of the firing patterns of neural ensembles. Apart from the complexities of ac...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(00)03072-9
更新日期:2000-12-22 00:00:00
abstract::The present study examines the brain-level representation and composition of meaning in scalar quantifiers (e.g., some), which have both a semantic meaning (at least one) and a pragmatic meaning (not all). We adopted a picture-sentence verification design to examine event-related potential (ERP) effects of reading inf...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2012.10.042
更新日期:2013-01-15 00:00:00
abstract::Previous evidence suggests that preterm newborns with intrauterine growth restriction (IUGR) have specific neurostructural and neurodevelopmental anomalies, but it is unknown whether these effects persist in early childhood. We studied a sample of 18 preterm IUGR, 15 preterm AGA - born between 26 and 34 weeks of gesta...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2011.01.032
更新日期:2011-03-25 00:00:00
abstract::Kallikrein hydrolyzes various biologically active peptides, other than kininogens, such as vasoactive intestinal polypeptide (VIP), in vitro. Since kallikrein and VIP have been immunohistochemically shown to be present in the perivascular areas of the pineal gland, this study was designed to determine their topographi...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/s0006-8993(98)00174-7
更新日期:1998-06-29 00:00:00
abstract::The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment conti...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(91)91182-z
更新日期:1991-10-18 00:00:00
abstract::The present study using near-infrared spectroscopy (NIRS) examined prefrontal activation associated with maze-solving performance in adult humans. The participants were required to solve a plus-shaped maze, comparable to the one used for pigeons and human children to behaviorally assess planning processes, by moving a...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2010.12.047
更新日期:2011-02-16 00:00:00
abstract::In the hippocampus, pyramidal cells (PCs) are not the only cell type sensitive to cholinergic stimulation. Two non-pyramidal cell types from animals as young as 8 days demonstrated clear, direct responses to application of cholinergic agonists. These cholinergic actions are excitatory, mostly blocked by muscarinic ant...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/0006-8993(91)91688-w
更新日期:1991-12-06 00:00:00
abstract::Insulin-like 6 immunoreactivity (irINSL6) was detected in Leydig cells of the mouse testis. In the brain, labeled somata were detected mainly in the caudal hypothalamus and midbrain. Double labeling the brainstem sections revealed that irINSL6 somata were 5-hydroxytryptamine (5-HT) positive. The presence of irINSL6 in...
journal_title:Brain research
pub_type: 杂志文章
doi:10.1016/j.brainres.2005.01.077
更新日期:2005-04-08 00:00:00