Potent ς1-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl) Piperidine Provides Ischemic Neuroprotection Without Altering Dopamine Accumulation In Vivo in Rats

Goyagi, Toru; Bhardwaj, Anish; Koehler, Raymond C.; Traystman, Richard J.; Hurn, Patricia D.; Kirsch, Jeffrey R.

doi:10.1213/00000539-200302000-00043

Cited by 19 publications

(14 citation statements)

References 39 publications

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“…All techniques are as previously described. 20,21 In brief, adult male Wistar rats (250 to 300 g; Harlan, Indianapolis, Ind) were anesthetized with halothane (1.0% to 2.0%) in air and allowed to ventilate spontaneously. Concentration of inspired oxygen was adjusted between 25% to 30% to maintain P a O 2 between 100 to 150 mm Hg.…”

Section: Mcao Modelmentioning

confidence: 99%

“…The femoral vein was cannulated, tunneled subcutaneously and exteriorized for vascular access and drug administration. 20,21 Rectal temperature was maintained throughout surgical procedures, during ischemia until emergence from anesthesia. Transient focal ischemia (2 hours) was produced by MCAO using an intraluminal suture technique in combination with laser-Doppler flowmetry (LDF) (Model MBF3D, Moor Instruments Ltd.) as previously described.…”

Section: Mcao Modelmentioning

confidence: 99%

“…Transient focal ischemia (2 hours) was produced by MCAO using an intraluminal suture technique in combination with laser-Doppler flowmetry (LDF) (Model MBF3D, Moor Instruments Ltd.) as previously described. 20,21 All experiments were performed in a blinded, randomized fashion. Rats were treated with continuous intravenous infusion of vehicle (saline) or 1 mg/Kg/hr BRL 52537 (Research Biochemical International) at onset (Rep-BRL), 2 hours (2 hr-BRL), 4 hours (4 hr-BRL) or 6 hours (6 hr-BRL) of reperfusion, and continued for 22 hours.…”

Section: Mcao Modelmentioning

confidence: 99%

“…The brain was harvested and sliced into seven 2-mm thick coronal sections for staining with 1% triphenyltetrazolium chloride (TTC) as previously described. 20,21 Infarct volume was measured by using digital imaging. The infarcted area was numerically integrated across each section and over the entire ipsilateral hemisphere.…”

Section: Chen Et Al Agonist In Focal Cerebral Ischemiamentioning

confidence: 99%

“…6,20 A microdialysis cannula (membrane length: 3 mm; cutoff: 6 KDaltons; CMA/Microdialysis AB, Stockholm, Sweden) was placed into the right CP complex using stereotactic surgery. 20 A 2-hour post-surgical equilibration period was given before the experiment began. Microdialysis cannula was then perfused with artificial cerebrospinal fluid at 1 L/min.…”

Section: Microdialysismentioning

confidence: 99%

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Prolonged Opportunity for Ischemic Neuroprotection with Selective κ-Opioid Receptor Agonist in Rats

Chen

Goyagi

Toung

et al. 2004

Stroke

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Background and Purpose-We have previously demonstrated that pretreatment with selective -opioid agonist BRL 52537 hydrochloride [(Ϯ)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine], provides ischemic neuroprotection following transient focal ischemia in rats. The present study was undertaken to a) define "therapeutic opportunity" for ischemic neuroprotection with BRL 52537, and b) determine if BRL 52537 attenuates ischemia-evoked efflux of dopamine and its metabolites in the striatum in vivo following transient focal ischemia. Methods-Using the intraluminal filament technique, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO). In a blinded, randomized fashion, rats were treated with saline (vehicle) or 1 mg/Kg/hr BRL 52537 infusion for 22 hours, initiated at onset, 2, 4, or 6 hours of reperfusion (Rep). In a separate set of experiments utilizing in vivo microdialysis, extracellular levels of dopamine and its metabolites were determined in the striatum during 2 hours of MCAO and 3 hours of reperfusion. Results-Infarct volume (% of contralateral structure; mean ϮSEM) in cortex was significantly attenuated when BRL 52537 was administered at reperfusion (22Ϯ6%), 2 hours (21Ϯ6%), and 4 hours (18Ϯ5%) compared with controls (39Ϯ5%). In striatum, infarct volume was significantly attenuated when BRL 52537 was administered at reperfusion (38Ϯ9%), 2 hours (40Ϯ8%), 4 hours (50Ϯ8%), and 6 hours (46Ϯ9%) as compared with controls (70Ϯ4%). A 6-to 8-fold increase in dopamine in microdialysates occurred within 40 minutes of MCAO. Pretreatment with BRL 52537 did not alter microdialysate levels of dopamine or its metabolites in the striatum during MCAO and early reperfusion, as compared with saline controls. Conclusions-These data demonstrate that BRL 52537 provides robust ischemic neurprotection with a long therapeutic opportunity (at least 6 hours) without altering ischemia-evoked efflux of dopamine (DA) and its metabolites in striatum during ischemia and early reperfusion.

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Section: Mcao Modelmentioning

confidence: 99%

Section: Mcao Modelmentioning

confidence: 99%

Section: Mcao Modelmentioning

confidence: 99%

Section: Chen Et Al Agonist In Focal Cerebral Ischemiamentioning

confidence: 99%

Section: Microdialysismentioning

confidence: 99%

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Prolonged Opportunity for Ischemic Neuroprotection with Selective κ-Opioid Receptor Agonist in Rats

Chen

Goyagi

Toung

et al. 2004

Stroke

Self Cite

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Striatal dopamine in bulimia nervosa: A pet imaging study

Broft

Shingleton

Kaufman

et al. 2012

Intl J Eating Disorders

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Objective Bulimia nervosa (BN) has been characterized as similar to an addiction, though the empirical support for this characterization is limited. This study utilized PET imaging to determine whether abnormalities in brain dopamine (DA) similar to those described in substance use disorders occur in BN. Method PET imaging with [11C]raclopride, pre/post methylphenidate administration, to assess dopamine type 2 (D2) receptor binding (BPND) and striatal DA release (ΔBPND). Results There was a trend towards lower D2 receptor BPND in two striatal subregions in the patient group compared to the control group. DA release in the putamen in the patient group was significantly reduced and, overall, there was a trend towards a difference in striatal DA release. Striatal DA release was significantly associated with the frequency of binge eating. Discussion These data suggest that BN is characterized by abnormalities in brain DA that resemble, in some ways, those described in addictive disorders.

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Insights into the Sigma‐1 receptor Chaperone's cellular functions: A microarray report

Tsai

Rothman

2011

Synapse

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We previously demonstrated that Sig-1Rs are critical regulators in neuronal morphogenesis and development via the regulation of oxidative stress and mitochondrial functions. In the present study, we sought to identify pathways and genes that are affected by Sig-1R. Gene expression profiles were examined in rat hippocampal neurons that had been cultured for18 days in vitro (DIV). The cells were transduced with AAV siRNA targeting Sig-1R on DIV 10 for 7 days, followed by gene expression analysis using a rat genome cDNA array. The gene array results indicated that Sig-1R knockdown hampered cellular functions including steroid biogenesis, protein ubiquitination, actin cytoskeleton network, and Nrf-2 mediated oxidative stress. Many of the cellular components important for actin polymerization and synapse plasticity, including F-actin capping protein and neurofilaments, were significantly changed in AAV-siSig-1R neurons. Further, cytochrome c was reduced in AAV-Sig-1R neurons whereas free-radical generating enzymes including cytochrome p450 and cytochrome b-245 were increased. The microarray results also suggest that Sig-1Rs may regulate genes that are involved in the pathogenesis of many CNS diseases including Alzheimer’s disease and Parkinson’s disease. These data further confirmed that Sig-1Rs play critical roles in the CNS and thus these findings may aid in future development of therapeutic treatments targeting neurodegenerative disorders.

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Potent ς1-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl) Piperidine Provides Ischemic Neuroprotection Without Altering Dopamine Accumulation In Vivo in Rats

Cited by 19 publications

References 39 publications

Prolonged Opportunity for Ischemic Neuroprotection with Selective κ-Opioid Receptor Agonist in Rats

Prolonged Opportunity for Ischemic Neuroprotection with Selective κ-Opioid Receptor Agonist in Rats

Striatal dopamine in bulimia nervosa: A pet imaging study

Insights into the Sigma‐1 receptor Chaperone's cellular functions: A microarray report

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