SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor

Noh, Su Jin; Lee, Jong Min; Lee, Ki Sung; Hong, Hye Jin; Lee, Chul Kyu; Cho, Il Hwan; Kim, Hye Sun; Suh, Yoo‐Hun

doi:10.1016/j.pbb.2011.07.018

Cited by 18 publications

(15 citation statements)

References 39 publications

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“…andrei was identified as the compound SP-8203, consisting two quinazoline-2,4-diones joined by an N-acetylspermine linker but its fluorescence spectra have not been analyzed in this paper [ 32 ]. Compound SP-8203 is pharmacologically potent in mammalian cells showing neuroprotective activity [ 33 ; 34 ]. The precise chemical characteristic of the M-fluorophore requires further analysis but that is not our current concern.…”

Section: Discussionmentioning

confidence: 99%

Asymmetrical hybridization and gene flow between Eisenia andrei and E. fetida lumbricid earthworms

et al. 2018

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Uniformly pigmented Eisenia andrei (Ea) and striped E. fetida (Ef) lumbricid earthworms are hermaphrodites capable of self-fertilization, cross-fertilization, and asymmetrical hybridization. The latter was detected by genotyping of F1 and F2 progeny of the controlled Ea+Ef pairs by species-specific sequences of maternal mitochondrial COI genes and maternal/paternal nuclear S28 rRNA genes. Among F1offspring there were self-fertilized Ea (aAA), Ef (fFF), and cross-fertilized fertile Ea-derived hybrids (aAF); the latter mated with Ea and gave new generation of Ea and hybrids, while mated with Ef gave Ea, Ef, Ea-derived hybrids and sterile Ef-derived hybrids (fFA). Coelomic fluid of Ea exhibits unique fluorescence spectra called here the M-fluorescence considered as a molecular biomarker of this species. Since similar fluorescence was detected also in some Ef (hypothetical hybrids?), the aim of present investigations was to identify the M-positive earthworms among families genotyped previously. It was assumed that factor/s responsible for metabolic pathways leading to production of undefined yet M-fluorophore might be encoded/controlled by alleles of hypothetical nuclear gene of Eisenia sp. segregating independently from species-specific S28 rRNA nuclear genes, where ‘MM’ or ‘Mm’ alleles determine M-positivity while ‘mm’ alleles determine M-negative phenotypes. Spectra of M-fluorescence were detected in all 10 Ea (aAAMM) and 19 Ea-derived hybrids (aAFMm), three of four Ef-derived hybrids (fFAMm) and one ‘atypical’ Ef (fFFMm) among 13 Ef earthworms. Among progeny of ‘atypical’ M-positive Ef (fFFMm) reappeared ‘typical’ M-negative Ef (fFFmm), confirming such hypothesis. Alternatively, the M-fluorescence might be dependent on unknown gene products of vertically-transmitted Ea-specific symbiotic bacteria sexually transferred to the Ef partner. Hypotheses of intrinsic and external origin of M-fluorescence might complement each other. The presence/absence of M-fluorophore does not correspond with body pigmentation patterns; Ef-characteristic banding appeared in posterior parts of hybrids body. In conclusion, Ea/Ef hybridization may serve for further studies on bi-directional gene flow.

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Section: Discussionmentioning

confidence: 99%

Asymmetrical hybridization and gene flow between Eisenia andrei and E. fetida lumbricid earthworms

et al. 2018

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“…A number of watermaze studies have been performed to determine the effect of MCAO on learning and memory deficits using either the Tamura model of permanent MCAO by electrocoagulation (e.g., Markgraf et al, 1992;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Yonemori et al, 1996) or the intraluminal thread model (e.g., Hayase et al, 2009;Kawanishi et al, 2010;Noh et al, 2011;Xu et al, 2009;Yun et al, 2007). It is important to note that with intraluminal thread models, particularly in mice, filament insertion can lead to loss of blood supply to the hippocampus (McColl et al, 2004), therefore although intraluminal thread is used as a model of MCAO, it is in fact capable of producing more widespread ischemia affecting other major blood vessel territories.…”

Section: Discussionmentioning

confidence: 99%

“…Understanding these functional deficits is essential for development of future therapies. Many experimental studies have used watermaze tasks to better understand spatial learning and memory deficits after MCA occlusion (MCAO) and to assess potential future therapies (Hayase et al, 2009;Kawanishi et al, 2010;Markgraf et al, 1992;Noh et al, 2011;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Wang et al, 2010;Xu et al, 2009;Yonemori et al, 1996;Yun et al, 2007;Zhang et al, 2010). However, in rodent experimental stroke models, investigation of deficits in spatial memory using the Morris watermaze may be confounded by coexisting sensory and motor impairments.…”

Section: Introductionmentioning

confidence: 99%

Watermaze Performance after Middle Cerebral Artery Occlusion in the Rat: The Role of Sensorimotor versus Memory Impairments

Bingham

Martin

Macrae

et al. 2012

J Cereb Blood Flow Metab

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In rodent stroke models, investigation of deficits in spatial memory using the Morris watermaze may be confounded by coexisting sensory or motor impairments. To target memory specifically, we devised a watermaze protocol to minimize the impact of sensory and motor impairments in female Lister-hooded rats exposed to proximal electrocoagulation of the middle cerebral artery (MCAO). Rats were trained in a reference-memory task comprising 4 trials/day; trial 1 being a probe trial (platform absent for the first 60 seconds). Training ended once animals reached a strict criterion based on the probe-trial performance. Memory retention was tested 1, 7, and 28 days later. The MCAO did not affect the number of days to reach criterion during acquisition or the time spent in target quadrant during retention testing, compared with sham or unoperated rats. However, MCAO rats showed slightly poorer accuracy in crossing the platform location and increased thigmotactic swimming compared with controls. Our results show that spatial memory deficits are minimal in this rodent stroke model, and suggest that previously published watermaze impairments are attributable to sensory and motor deficits but not memory deficits. We recommend using probe trials and training to a predetermined performance criterion in future studies assessing watermaze memory deficits in rodent stroke models.

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“…No clinical trials with metabotropic glutamate receptor antagonists have been conducted. It was recently reported that SP-8203, an NMDA antagonist, has dual effects that protect cells against excitotoxicity and improve memory in brain ischemic injuries [69], suggesting a potential therapeutic role of SP-8203 in cerebral ischemic injuries.…”

Section: Other Therapeutic Strategies For Ischemic Strokementioning

confidence: 99%

Advances in stroke therapy

Jaffer

Morris

Stewart

et al. 2011

Drug Deliv. and Transl. Res.

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Stroke is a leading cause of death, long-term disability, and socioeconomic costs, highlighting the urgent need for more effective treatments. Intravenous administration of tissue plasminogen activator (t-PA) is the only FDA-approved therapy to re-establish cerebral blood flow. However, because of increased risk of hemorrhage beyond 3 h post stroke, few stroke patients (1–2%) benefit from t-PA; t-PA, which has neurotoxic effects, can also aggravate the extent of reperfusion injury by increasing blood-brain barrier permeability. An alternative strategy is needed to extend the window of intervention, minimize damage from reperfusion injury, and promote brain repair leading to neurological recovery. Reactive oxygen species (ROS), generated soon after ischemia and during reperfusion and thereafter, are considered the main mediators of ischemic injury. Antioxidant enzymes such as catalase, superoxide dismutase, etc. can neutralize ROS-mediated injury but their effective delivery to the brain remains a challenge. In this article, we review various therapeutic approaches including surgical interventions, and discuss the potential of nanoparticle-mediated delivery of antioxidants for stroke therapy.

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SP-8203 shows neuroprotective effects and improves cognitive impairment in ischemic brain injury through NMDA receptor

Cited by 18 publications

References 39 publications

Asymmetrical hybridization and gene flow between Eisenia andrei and E. fetida lumbricid earthworms

Asymmetrical hybridization and gene flow between Eisenia andrei and E. fetida lumbricid earthworms

Watermaze Performance after Middle Cerebral Artery Occlusion in the Rat: The Role of Sensorimotor versus Memory Impairments

Advances in stroke therapy

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