Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats

Allahtavakoli, Mohammad; Jarrott, Bevyn

doi:10.1016/j.brainresbull.2011.03.019

Cited by 69 publications

(46 citation statements)

References 31 publications

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“…In vitro studies revealed potent neuroprotective effects of sigma-1R agonists after excitotoxic damage [18], hypoxia-mediated neurotoxicity [41], oxidative stress-induced cell death [17], or glucose deprivation [42]. In vivo studies demonstrated that sigma-1R agonists exert therapeutic actions in rats after stroke [19,20], after selective cholinergic lesions [43], and after spinal root avulsion [10]. The results found in this study also reveal a potent neuroprotective effect of PRE-084 administration on spinal MNs in the neurodegenerative SOD1 G93A mice model.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it is related to some central nervous system pathologies, including depression, schizophrenia, drug addiction, and Alzheimer disease [13][14][15][16]. Several studies have demonstrated potent therapeutic actions of sigma-1R agonists, reducing glutamate-mediated cell death [17,18] or modulating the inflammatory reaction after stroke in rats [19,20]. Luty et al [21] and Al-Saif et al [22] recently reported a novel mutation of sigma-1R in patients affected by ALS, suggesting that pharmacological interventions targeting this receptor could be a good therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

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Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

et al. 2012

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Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1 G93A mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1 G93A animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca 2+ influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

et al. 2012

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“…Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783 Ligands for rR1 have shown neuroprotective properties in several animal models including amyotrophic lateral sclerosis (ALS), 25 stroke, 26 and diabetic retinopathy. 27 In addition to neuroprotection, rR1 activation has been associated with decreased reactive gliosis in both the ALS mouse model and the rat stroke injury model.…”

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confidence: 99%

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Zhao

Liou

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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“…During the surgery, inflammatory mediators, like C-reactive protein, cortisol hormone and cytokines, are released in large abundance, which activate the inflammatory cells and constantly exacerbate the inflammatory responses. A researcher proposed that the balance between pro-inflammatory cytokines (IL-8 and tumor necrosis factor-α) and antiinflammatory cytokines (IL-4 and IL-10) was beneficial to eliminating the adverse impacts result from traumatic inflammatory responses and promoting the recovery of diseases (Allahtavakoli et al, 2011;de Lima et al, 2011;Sun et al, 2011;Gäbel et al, 2013;Shen et al, 2013;Verit et al, 2013;Yang et al, 2013;Zhao et al, 2013;Guo et al, 2014;Kma et al, 2014;Lu et al, 2014;Pandurangan et al, 2014;Soliman et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Influence of Propofol, Isoflurane and Enflurance on Levels of Serum Interleukin-8 and Interleukin-10 in Cancer Patients

Liu

2014

Asian Pacific Journal of Cancer Prevention

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Objective: To observe the influence of propofol, isoflurane and enflurance on interleukin-8 (IL-8) and IL-10 levels in cancer patients. Methods: Ninety cancer patients with selective operation from March 2011 to May 2014 were randomly divided into group A (34 cases), group B (28 cases) and group C (28 cases). Intramuscular injections of scopine hydrochloride and phenobarbital sodium were routinely conducted to 3 groups. After general anesthesia was induced, tracheal intubations were given. During the maintenance of anesthesia, 0.5~1.0 mg/ kg propofol was intravenously injected to group A discontinuously, while continuous suctions of isoflurane and enflurance were subsequently performed to group B and C correspondingly. Clinical outcomes, postoperative complications as well as serum IL-8 and IL-10 levels before operation (T0), at the time of skin incision (T1), 3 h after the beginning of the operation (T2) and 24 h (T3) and 72 h (T4) after the operation were observed among 3 groups. Results: Operations in all groups were successfully completed. The rates of surgery associated complications were 8.82% (3/34), 7.14% (2/28) and 7.14% (2/28) in group A, B and C, respectively, and there were no significant differences (P>0.05). Serum IL-8 and IL-10 levels increased gradually from the beginning of the operation and reached the peak at T3, and were evidently higher at each time point than at T0 (P<0.01). At T1, serum IL-8 and IL-10 levels had no significant differences among 3 groups (P>0.05), but the differences were significant at T2, T3 and T4 (P<0.05). Moreover, correlation analysis suggested that serum IL-8 level was in positive relation with IL-10 level (r=0.952, P<0.01). Conclusions: Propofol, which is better in inhibiting serum IL-8 secretion and improving IL-10 secretion than isoflurane and enflurance, can be regarded as a preferable anesthetic agent in inhibiting traumatic inflammatory responses.

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Sigma-1 receptor ligand PRE-084 reduced infarct volume, neurological deficits, pro-inflammatory cytokines and enhanced anti-inflammatory cytokines after embolic stroke in rats

Cited by 69 publications

References 31 publications

Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

Sigma-1R Agonist Improves Motor Function and Motoneuron Survival in ALS Mice

Sigma Receptor Ligand, (+)-Pentazocine, Suppresses Inflammatory Responses of Retinal Microglia

Influence of Propofol, Isoflurane and Enflurance on Levels of Serum Interleukin-8 and Interleukin-10 in Cancer Patients

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