Blocking the P2X7 receptor improves outcomes after axonal fusion.

Rodriguez-Feo CL, Sexton KW, Boyer RB, Pollins AC, Cardwell NL, Nanney LB, Shack RB, Mikesh MA, McGill CH, Driscoll CW, Bittner GD, Thayer WP
J Surg Res. 2013 184 (1): 705-13

PMID: 23731685 · PMCID: PMC3759537 · DOI:10.1016/j.jss.2013.04.082

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Action Potentials Adenosine Triphosphate Animals Axons Benzenesulfonates Coloring Agents Drug Carriers Male Motor Activity Nerve Regeneration Neurosurgical Procedures Platelet Aggregation Inhibitors Polyethylene Glycols Purinergic P2X Receptor Antagonists Rats Rats, Sprague-Dawley Receptors, Purinergic P2X7 Sciatic Neuropathy Wallerian Degeneration Wound Healing

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