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J Surg Res ; 184(1): 705-13, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23731685

RESUMO

BACKGROUND: Activation of the P2X7 receptor on peripheral neurons causes the formation of pannexin pores, which allows the influx of calcium across the cell membrane. Polyethylene glycol (PEG) and methylene blue have previously been shown to delay Wallerian degeneration if applied during microsuture repair of the severed nerve. Our hypothesis is that by modulating calcium influx via the P2X7 receptor pathway, we could improve PEG-based axonal repair. The P2X7 receptor can be stimulated or inhibited using bz adenosine triphosphate (bzATP) or brilliant blue (FCF), respectively. METHODS: A single incision rat sciatic nerve injury model was used. The defect was repaired using a previously described PEG methylene blue fusion protocol. Experimental animals were treated with 100 µL of 100 µM FCF solution (n = 8) or 100 µL of a 30 µM bzATP solution (n = 6). Control animals received no FCF, bzATP, or PEG. Compound action potentials were recorded prior to transection (baseline), immediately after repair, and 21 d postoperatively. Animals underwent behavioral testing 3, 7, 14, and 21 d postoperatively. After sacrifice, nerves were fixed, sectioned, and immunostained to allow for counting of total axons. RESULTS: Rats treated with FCF showed an improvement compared with control at all time points (n = 8) (P = 0.047, 0.044, 0.014, and 0.0059, respectively). A statistical difference was also shown between FCF and bzATP at d 7 (P < 0.05), but not shown with d 3, 14, and 21 (P > 0.05). CONCLUSIONS: Blocking the P2X7 receptor improves functional outcomes after PEG-mediated axonal fusion.


Assuntos
Procedimentos Neurocirúrgicos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/fisiologia , Neuropatia Ciática/tratamento farmacológico , Neuropatia Ciática/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Animais , Axônios/efeitos dos fármacos , Axônios/fisiologia , Benzenossulfonatos/farmacologia , Corantes/farmacologia , Portadores de Fármacos/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Inibidores da Agregação Plaquetária/farmacologia , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Degeneração Walleriana/tratamento farmacológico , Degeneração Walleriana/fisiopatologia , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
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