Neuropraxia following nerve sparing radical prostatectomy is associated with increased expression of markers of inflammation and Fidgetin-2 like protein
Villegas, G1; Tar, M1; Baker, L1; Sharp, D1; Davies, K1
1: Albert Einstein College of Medicine, United States
Objectives: Radical prostatectomy (RP) carries a high risk of erectile dysfunction (ED) as a result of neuropraxia. Neuropraxia also occurs when nerve sparing procedures are utilized. Preliminary data from our group has demonstrated that a previously uncharacterized microtubule severing enzyme that controls axonal growth in vitro, called Fidgetin-like 2 protein (FL2), is rapidly upregulated in the major pelvic ganglion (MPG) following cavernous nerve (CN) transection. Interestingly, animals that undergo surgical procedures without CN transection (SHAM), also had increased FL2 protein and mRNA expression. The objective of the present study was to test the hypothesis that even in the absence of direct damage to the CN, trauma associated with nerve sparing RP triggers an inflammatory and FL2 response which results in neuropraxia and thereby ED.
Materials and Methods: ~300g Sprague Dawley Rats were subjected to bilateral nerve transection surgery (CNI) or (SHAM). Animals were sacrificed at 6h, 2days and 3 days post-surgery and both MPG removed and total protein and RNA isolated. FL2 expression was assessed by western Blot and RT-qPCR. Immune factors were assayed by RT-qPCR.
Results: FL2 expression is dramatically upregulated in the MPG 6 hours after CN injury, but levels of FL2 return to baseline by Day 3. Interestingly, in sham control animals we observed that FL2 expression levels were increased at 3-days post-surgery compared to the 6 h control. In addition, expression of the inflammatory markers, NFkβ-activating protein (Nkap), VCAM, VEGF, NGF and ROCK2 were also increased, whereas HO-1 was significantly decreased in the MPG of SHAM animals 3 days post-surgery compared to the levels at 6-hours. We observed a statistically significant correlation between expression of FL2 mRNA and Nkap, VCAM and ROCK2 mRNAs.
Conclusions: Our data demonstrates that during acute CN injury there are rapid changes in the expression of FL2 and inflammatory factors in the MPG as part of a response mechanism to direct nerve injury. However, when there is surgical trauma that does not directly damage the CN, an inflammatory response is initiated associated with a delayed activation of FL2 in the MPG. Activation of FL2 may result from a direct response to specific inflammatory pathways or indirectly as a response to CN injury caused by the inflammatory response.
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