Search

The immunophilin-ligand FK506 has been shown to ameliorate erectile function and preserve cavernous nerve (CN) architecture in short-term-studies using rat models of CN injury.The aim of this series was to ascertain the optimal dose and timing of FK506 administration in this animal model.Rats underwent bilateral CN crush and were treated with FK506 at different time points. There were control (C) and sham groups for each time point. Based on preliminary experiments, the CN-crush rats had no treatment (C) or either FK506 1 mg/kg (BL) or 3.2 mg/kg (BH) for 3 days prior to and the day of CN crush (PRE), on the day of and for 3 days following CN crush (POST) and for 3 days pre-, on the day of, and 3 days post-CN crush (PP).All animals had measurement of intracavernosal pressure/mean arterial blood pressure (ICP/MAP) ratios at 28 days post-CN crush. Structural analysis was conducted in the POST groups. Penile tissue was assessed for apoptosis with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay and immunohistochemically for neural factors (growth associated protein 43 [GAP43], nerve growth factor [NGF], and neural nitric oxide synthase [nNOS]). The CN architecture was examined by transmission electron microscopy (TEM).Sham animals had an ICP/MAP ratio of 70%. Only the BH-POST group revealed an improved ICP/MAP ratio compared with C (50 +/- 9% vs. 32 +/- 8%, P0.01). nNOS staining was significantly restored reaching sham levels in BL-POST and BH-POST groups vs. C (P0.05). NGF and GAP43 staining displayed no significant differences between C and treatment groups (P0.05). Apoptosis was significantly reduced in BL-POST and BH-POST groups compared with C (16 +/- 4%, 21 +/- 9%, and 63 +/- 7%, P0.001). TEM exhibited preservation of CN architecture for BH-POST compared with C.These results suggest that short-term treatment with doses of FK506 higher than previously utilized preserves erectile function in the rat CN-injury model. Pretreatment appears to offer no advantage. However, FK506 administration just prior to CN injury and for a short-time post-injury achieves the best functional and structural preservation outcomes.

Introduction Cavernosal oxygenation appears to be important for preservation of erectile tissue health. Hyperbaric oxygen therapy (HBOT) has been shown to improve tissue oxygenation and has neuromodulatory effects. Aim This study was designed to define the effects of HBOT on erectile function (EF) and cavernosal tissue in the rat cavernous nerve (CN) injury model. Methods Four groups of Sprague-Dawley rats were studied: rats with bilateral CN crush, HBOT treated (Crush+/HBOT+); bilateral CN-crush/no HBOT (C+/H−); no crush/no HBOT (C−/H−); and no crush/HBOT (C−/H+). HBOT was delivered daily for 90 minutes at three atmospheres for 10 days commencing the day of CN crush. Main Outcome Measures Ten days after CN injury, the animals underwent CN stimulation measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios. Corporal tissue was harvested pre-sacrifice, and immunohistochemically stained for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), and cluster of differentiation molecule (CD31). Histologic analysis was performed for Masson's trichrome to assess the smooth muscle–collagen ratio. Terminal deoxynucleotidyl transferase Biotin-dUTP Nick End Labeling assay was used to define apoptotic indices (AIs). Results The C+/H− group had significantly lower ICP/MAP ratios compared with C−/H− rats, (31% vs. 70%, P P = 0.005). NGF and eNOS staining densities were higher in C+/H+ rats compared with C+/H− rats ( P P P Conclusion HBOT following a CN injury improved EF preservation in this model, supporting the cavernosal oxygenation concept as protective mechanism for EF. The effects appear to be mediated via preservation of neurotrophic and endothelial factor expression. Muller A, Tal R, Donohue JF, Akin-Olugbade Y, Kobylarz K, Paduch D, Cutter SC, Mehrara BJ, Scardino PT, and Mulhall JP. The effect of hyperbaric oxygen therapy on erectile function recovery in a rat cavernous nerve injury model