(+)-Pentazocine attenuates SH-SY5Y cell death, oxidative stress and microglial migration induced by conditioned medium from activated microglia.

BACKGROUND: Sigma receptors (σ1R) are expressed both in neurons and microglia and can be considered as a promising target for developing pharmacological strategies for neuroprotection in various experimental models. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1R agonist, in an in vitro model of neuron/microglia crosstalk following hypoxia/reoxygenation. METHODS: Microglia (BV2 cells) was exposed (3h) to 1% oxygen and reoxygenation was allowed for 24h. Conditioned media obtained from this experimental condition was used to treat neuroblast-like cell line (SH-SY5Y cells) in the presence or absence of (+)-pentazocine (25µM). Cell viability was measured by cytofluorimetric analysis, whereas inflammation and oxidative stress were evaluated by the expression of Hsp70, GAD, SOD and p65. Microglial cell migration was also evaluated by Xcelligence technology. RESULTS: Our results showed that (+)-pentazocine was able to increase SH-SY5Y cell viability following exposure to microglial-conditioned medium. Furthermore, (+)-pentazocine was also able to inhibit microglial cell toward neuron treated with hypoxic conditioned medium. Finally, pharmacological treatment reduced the expression of inflammatory and oxidative stress markers (GAD, SOD and p65). Interestingly, hypoxic medium was able to reduce the expression of Hsp70 and such effect was prevented by (+)-pentazocine treatment. CONCLUSIONS: (+)-Pentazocine exhibits significant neuroprotective effects in our in vitro model of SH-SY5Y/microglial crosstalk thus suggesting that σ1R may represent a possible strategy for neuroprotection.

(+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury.

BACKGROUND: Sigma-1 receptors (σ1R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1R agonist, in an in vitro model of microglia activation. METHODS: Microglia (BV2 cells) was exposed (3h) to 1% oxygen and reoxygenation was allowed for 24h. Cells were treated with different concentrations (1, 10, 25 and 50µM) of (+)-pentazocine in the presence or absence of NE-100 (1µM), a well established σ1R antagonist. Cell viability and apoptosis were measured by cytofluorimetric analysis, whereas oxidative stress was evaluated by reduced glutathione (GSH) content and mitochondrial potential analysis. RESULTS: Our results showed that (+)-pentazocine was able to increase cell viability and restore mitochondrial potential at all concentrations whereas only 1 and 10µM were able to reduce significantly apoptotic cell death, to restore reduced glutathione intracellular content and prevent ERK1/2 phosphorylation. All these effects were abolished by concomitant treatment with NE-100. CONCLUSIONS: (+)-pentazocine exhibits significant dose dependent protective effects in our in vitro model of microglial activation thus suggesting that σ1R may represent a possible target for neuroprotection.

5-ALA fluorescence-assisted surgery in pediatric brain tumors: report of three cases and review of the literature.

5-aminolevulinic acid (5-ALA) has been used for the last 5 years to increase the extent of resection in adult brain tumors, mostly glioblastomas, but it is not approved yet as standard adjuvant treatment in the pediatric population. We report three different cases of pediatric brain tumors (two glioblastomas and one medulloblastoma) recently operated using 5-ALA fluorescence guidance, highlighting how useful it is in pediatric high-grade glioma (but not in medulloblastoma) also and confirming the lack of 5-ALA-related side effects. The first glioma was a recurrent GBM, whilst the second was a primary tumor. In all children, 5-ALA was administrated after discussing its use, including pros and cons, with the parents. 5-ALA fluorescence was a very useful tool to better identify tumor tissue and achieve gross-total tumor resection in GBMs, as confirmed by postoperative magnetic resonance imaging (MRI). In the medulloblastoma case no useful 5-ALA fluorescence was identified. No hematological or dermatological complications nor other side effects related to use of 5-ALA were observed. We submit that 5-ALA fluorescence guided surgery can be safe and useful in pediatric high-grade glioma, although its use in children still remains an off-label indication and requires validation through larger studies.