Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview

Abstract

In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.

The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research

“…Figure 1. Comparative anatomy illustrations of the male pelvic cavity, sagittal view: (A) in humans; (B) in rats [23].…”

“…This allows for an empirical evaluation of CN lesion-induced conduction deficits and the functional outcomes of restorative interventions. Such evaluations are conducted through comparative analyses of alterations in ICP values, relative to MAP, achieved via standardized electrostimulation of the CNs, unilaterally or bilaterally, pre-and post-injury and/or therapeutic intervention [23].…”

“…These conditions will impact EF independently, both in the preoperative setting, lowering baseline functionality, but also preoperatively, making the impact of post-RP CN damage a more complex topic in the real-life clinical PCa demographic. Conversely, especially in chronic studies, not allowing for a sufficient washout period for the therapeutics administered between stimulation response measurements may lead to a misinterpretation of EF recovery due to the continued presence and effects of experimental interventions [23].…”

“…Typically, as shown in Figure 2, bilateral dissection of the CNs for injury and electrostimulation, along with cannulation of the carotid artery and corpus cavernosum, for MAP and ICP measurements, respectively, are integral components for achieving experimental accuracy [38]. In terms of standardizing CN surgical injuries, the crush lesion model is generally favored for systemic and topical intraoperative treatment studies, as opposed to the more radical cut lesion models, which necessitate subsequent micro-neurorraphy for repair [23].…”

“…Caution must be exercised to avoid any disruption of superficial veins, and if necessary, cautery can be applied to manage any potential bleeding. Moving forward, throughout the surgery, the wound is irrigated with normal saline to prevent tissue desiccation [23,38].…”