Abstract：
:The nitric oxide (NO) metabolome and the NO metabolite-based neurovascular protective pathways are dysregulated after stroke. The major NO metabolite S-nitrosoglutahione (GSNO) is essential for S-nitrosylation-based signaling events and the inhibition of S-nitrosoglutahione (GSNO)-metabolizing enzyme GSNO reductase (GSNOR) provides protective effects following cardiac ischemia. However, the role of GSNOR and GSNOR inhibition-mediated increased GSNO/S-nitrosylation is not understood in neurovascular diseases such as stroke. Because age is the major risk factor of stroke and recovery in aged stroke patients is low and slow, we investigated the efficacy of GSNOR inhibition using a GSNOR selective inhibitor N6022 in a clinically relevant middle-aged cerebral ischemia and reperfusion (IR) mouse model of stroke. N6022 (5 mg/kg; iv) treatment of IR mice at 2 h after reperfusion followed by the treatment of the same dose daily for 3 days reduced the infarct volume and decreased the neurological score. Daily treatment of IR animals with N6022 for 2 weeks significantly improved neurological score, brain infarctions/atrophy, survival rate, motor (measured by cylinder test) and cognitive (evaluated by novel object recognition test) functions which paralleled the decreased activity of GSNOR, reduced levels of peroxynitrite and decreased neurological score. These results are the first evidence of a new pathway for the treatment of stroke via the inhibition of GSNOR. Based on the efficacy of N6022 in the stroke animal model and its use in human therapeutic studies without toxicity, we submit that GSNOR is a druggable target, and N6022 is a promising drug candidate for human stroke therapy.
journal_name
Brain Resjournal_title
Brain researchauthors
Khan M,Kumar P,Qiao F,Islam SMT,Singh AK,Won JS,Feng W,Singh Idoi
10.1016/j.brainres.2020.146879subject
Has Abstractpub_date
2020-08-15 00:00:00pages
146879eissn
0006-8993issn
1872-6240pii
S0006-8993(20)30235-3journal_volume
1741pub_type
杂志文章相关文献
BRAIN RESEARCH文献大全abstract：:In several rodent species social play appears to be necessary for proper deployment of species-specific patterns of aggressive and reproductive behavior. Specifically, in male Syrian hamsters (Mesocricetus auratus), play has been linked to the development of adult aggression. We quantified several types of social play...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2019.02.012
更新日期：2019-06-01 00:00:00
abstract：:In this report, using a push-pull perfusion technique, we examined in vivo the effects of exogenous dopamine (DA) on the output of neurochemical substances from the caudate nucleus (CN) of freely behaving rats. Exogenous DA, at concentrations of 10(-5) M, 5 x 10(-5) M and 10(-4) M, in modified Krebs-Ringer phosphate m...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(89)90803-2
更新日期：1989-03-06 00:00:00
abstract：:We report here the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0165-3806(85)90260-3
更新日期：1985-02-01 00:00:00
abstract：:Noradrenergic and dopaminergic regulation of thyrotropin (TSH) secretion was investigated in adult male Wistar rats. TSH secretion displayed a circadian variation with peak serum TSH levels at 10.00 h. The alpha 2-adrenoceptor agonist, clonidine (250 micrograms/kg, i.p.), was found to cause an enhancement of serum TSH...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(87)91378-3
更新日期：1987-02-24 00:00:00
abstract：:Dentate granule cells can be selectively destroyed by intrahippocampal injections of colchicine. This study evaluates the consequences of granule cell destruction on blood pressure regulation in the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR). Bilateral destruction of dentate granule cells...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(94)91473-7
更新日期：1994-09-12 00:00:00
abstract：:Pharmacological studies have documented that altered drug responses, particularly to benzodiazepines, are common in elderly populations. While numerous factors may contribute to changes in drug response, age-related alterations in the molecular composition of GABA(A) receptors may be a key factor in regulating these r...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2005.12.036
更新日期：2006-02-16 00:00:00
abstract：:Data are presented which show a different pattern of dopamine and noradrenaline utilization in terminal regions of the A9 and A10 dopaminergic systems and in terminal regions of the dorsal noradrenergic bundle after electrical stimulation of the ventral tegmental area and an adjacent area. At the sites of the electrod...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(83)90505-x
更新日期：1983-06-06 00:00:00
abstract：:To test the hypothesis that enkephalins, substance P, bradykinin and angiotensin II could act as neurohumoral modulators of hypothalamic function, these peptides (0.01-20 microgram) were injected into the general circulation of anesthetized rats, and changes in hypothalamo-neurohypophysial activity were determined by ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(81)90214-6
更新日期：1981-09-07 00:00:00
abstract：:Stanniocalcin (STC-1), a 50 kDa glycoprotein hormone that regulates calcium/phosphate homeostasis in bony fish and mammals, has been shown to be expressed in central neurons and choroid plexus, and to exert a protective effect against hypercalcemic and hypoxic damage to neurons. Circumventricular organs are known to f...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2008.04.070
更新日期：2008-07-07 00:00:00
abstract：:The neuronal threshold, which can be determined by the level of depolarization immediately prior to spike generation, is different for responses to conditioned and discriminated stimuli after conditioning. However, it is impossible to determine excitability within a response to stimuli that failed to generate a spike....
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(02)02868-8
更新日期：2002-08-09 00:00:00
abstract：:The effect of potassium depolarization on dopamine D1 receptor activity in bovine retina was investigated. Preincubation of bovine retinas in buffer containing high KCl (56 mM) as compared to a low KCl control buffer resulted in a significant decrease in dopamine-stimulated adenylate cyclase activity with no change in...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(90)91555-u
更新日期：1990-06-25 00:00:00
abstract：:Recent radioligand binding studies demonstrated an increase in the density of dopamine D2 receptors in the nucleus accumbens ipsilateral to the stimulating electrode in amygdala- or hippocampal-kindled rats. In the present study we examined the anticonvulsant effect of dopamine agonists by unilateral microinjections i...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(91)90822-d
更新日期：1991-07-12 00:00:00
abstract：:Nerve growth factor (NGF) transported intraaxonally from the adrenergic nerve terminals in the iris to the cell bodies in the superior cervical ganglion resulted in an increase in the activity of the enzyme ornithine decarboxylase in the ganglion. This occurred in both six-day-old and adult rats with the relative effe...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(80)91092-6
更新日期：1980-10-27 00:00:00
abstract：:Astrogliogenesis in the human fetal cerebellum was examined in 46 cerebella obtained from hysterotomy specimens ranging between 9 and 20 weeks of ovulation age. By correlating the results obtained by rapid Golgi and Golgi-Cox methods, the indirect immunofluorescence technique for glial fibrillary acidic protein, and e...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(80)90280-2
更新日期：1980-05-26 00:00:00
abstract：:The spiral ganglion accommodates the cell bodies of the acoustic nerve fibres connecting the hair cells to the central nervous system. As the ionic channels containing various voltage-gated K+ channel (Kv) subunits play pivotal roles in determining the functional properties and firing behaviour of the spiral ganglion ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2008.02.072
更新日期：2008-05-19 00:00:00
abstract：:Sex differences in cocaine's mechanisms of action and behavioral effects have been widely reported. However, little is known about how sex influences intracellular signaling cascades involved with drug-environment associations. We investigated whether ERK/CREB intracellular responses in the mesocorticolimbic circuitry...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2013.04.060
更新日期：2013-07-03 00:00:00
abstract：:The effect of microinfusions of cholecystokinin octapeptide (CCK8) and its antagonist L364,718 on duodenal and jejunal motility were evaluated by electromyography in fasted and fed rats. The rats were chronically fitted with electrodes implanted on the duodeno-jejunal wall. Steel cannulas were placed bilaterally in ei...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(90)91124-y
更新日期：1990-01-29 00:00:00
abstract：:We studied whether the antinociceptive effect produced by intracerebroventricular injection of delta-sleep-inducing peptide (DSIP) to mice involved the monoaminergic pathways that descended from brainstem to spinal cord (the descending inhibitory systems). In the tail-pinch test, the antinociceptive effect of DSIP was...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(89)91569-2
更新日期：1989-02-20 00:00:00
abstract：:Horseradish peroxidase injections into the medulla of tadpoles demonstrate, by back-filling, efferent neurons in the torus semicircularis which project to the ipsilateral superior olive. This projection, as well as one to the vicinity of the efferent neurons of the contralateral VIII and lateral line nerves, is confir...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(84)90774-1
更新日期：1984-02-06 00:00:00
abstract：:Medium conditioned by NG108-15 neuroblastoma x glioma hybrid cells contains a factor which increases the number of acetylcholine receptor (AChR) aggregates on cultured myotubes. Protease digestion indicates that the AChR aggregation factor is a protein, and the molecular weight is from 150,000 to 250,000 daltons as es...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(81)90161-x
更新日期：1981-03-30 00:00:00
abstract：:Administration of benzodiazepines at appropriate times in the circadian cycle induce phase-shifts in circadian locomotor activity. The possibility that benzodiazepine-induced shifts are mediated at the level of the suprachiasmatic nuclei (SCN), identified as the circadian pacemaker in mammals, was examined electrophys...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(91)90659-j
更新日期：1991-06-21 00:00:00
abstract：:Ethanol administration in long-sleep (LS) and short-sleep (SS) mice results in a large number of Fos-IR neurons in the supraoptic nucleus (SON) in LS, and almost no Fos-IR neurons in the same nucleus in SS mice. In contrast, isotonic saline, hypertonic saline, with or without ethanol, resulted in a similar pattern of ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(02)02453-8
更新日期：2002-05-10 00:00:00
abstract：:The present study was designed to investigate the role of activation of Kca+2 channels and cAMP in opioid-induced pial artery dilation in newborn pigs equipped with closed cranial windows. Methionine enkephalin, an endogenous mu agonist, elicited dilation that was modestly attenuated by the Kca+2 channel antagonist, i...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(96)01284-x
更新日期：1997-02-07 00:00:00
abstract：:Classical anatomical depictions of the cervical sympathetic trunk label it as a cholinergic preganglionic structure. We studied the cervical sympathetic trunk of the rat following daily injection for 5 weeks of guanethidine monosulphate, a regimen known to selectively destroy adrenergic neurons outside of the blood-br...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(89)91101-3
更新日期：1989-10-02 00:00:00
abstract：:Immobilization of frogs for 1 h induces analgesia which is blocked but not reversed by low doses of naloxone. After 9 days of daily immobilization for 1 h, the treatment fails to cause analgesia thus indicating that tolerance has developed. Animals tolerant to immobilization-induced analgesia do not show cross-toleran...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(84)90073-8
更新日期：1984-04-02 00:00:00
abstract：:Antisense oligodeoxynucleotides (ODNs) are used for the selective inhibition of gene expression. Antisense ODNs are promising tools for the investigation of physiological implications of proteins in the central nervous system of rodents in vivo. We have previously demonstrated that a phosphorothioate antisense ODN to ...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(97)00463-0
更新日期：1997-08-08 00:00:00
abstract：:It has been suggested that thiolic groups are essential for cytochrome c oxidase (COX) activity and other respiratory mitochondrial enzymes. Recent experiments showed that the thiolic antioxidant N-acetylcysteine (NAC) can protect against age-related impairment in COX activity in mice hepatic mitochondria. The present...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/s0006-8993(99)01819-3
更新日期：1999-09-18 00:00:00
abstract：:Invasion of scrapie agent into the central nervous system (CNS) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. Comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and c...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(86)90048-x
更新日期：1986-09-24 00:00:00
abstract：:Equivalent antiinflammatory doses of steroids including betamethasone, methylprednisolone and dexamethasone were administered in the neonatal period in a rat model. In situ cell death in hippocampus quantified by Terminal Deoxynucleated Transferase Nick-End Labeling and on ratio of brain to body weight was investigate...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/j.brainres.2008.10.051
更新日期：2009-01-23 00:00:00
abstract：:This work describes the change in an active electrogenesis of the command neurons responsible for defensive closure of a snail's pneumostome during elaborating, extinction and restoration of a classical conditioned defensive reflex to a tactile stimulus. Tactile stimulations applied to different parts of a snail's bod...
journal_title：Brain research
pub_type： 杂志文章
doi：10.1016/0006-8993(92)91453-l
更新日期：1992-11-06 00:00:00
