The neuro-protective and tissue-protective properties of platelet-rich plasma (PRP) have been demonstrated through treating bilateral cavernous nerve (CN) injury in rats, although the underlying mechanisms have not been fully clarified. To determine factors released from PRP and explore their role in mediating preservation of erectile function (EF) in a rat model of CN injury. Male Sprague-Dawley rats (aged 10 weeks) were used in this study. 6 rats were used to obtain blood for PRP and whole plasma preparation. We probed samples using a cytokine antibody array and performed enzyme-linked immunosorbent assay (ELISA). We determined the expression patterns of C-X-C motif chemokine ligand 5 (CXCL5) and receptors in the major pelvic ganglion (MPG) and corpus cavernosum via immunostaining. 32 rats were divided into 4 groups based on the type of injection received: (i) sham, (ii) vehicle, (iii) 400 μL of PRP, and (iv) 30 ng/kg of CXCL5. Groups 2-4 were subjected to bilateral CN crush (BCNC) injury. 4 weeks later, EF was assessed by CN electrostimulation, and CNs and penile tissue were collected for histological analysis. Cytokine antibody array, ELISA, erectile response, and immunofluorescence staining readings. The PRP contained high levels of CXCL5. MPG neurons expressed CXCL5 and CXCR2. PRP intracavernous injection stabilized CXCR2 and increased CXCL5 expression in the MPG after BCNC, thus enhancing neuroprotection. CXCL5 injection improved BCNC-induced erectile dysfunction by preventing smooth muscle atrophy. The therapeutic efficacy of PRP in CN injury-induced erectile dysfunction may arise from the synergy among multiple biomolecules. Our study serves as a basis for future studies on PRP formulation to provide safe and effective medications for the maintenance of EF after radical prostatectomy in patients with prostate cancer. A strength of our study is that our model was able to isolate the role of cytokines, specifically CXCL5, as part of the mechanism responsible for PRP's protective properties. However, the rat cytokine array provided limited experimental targets. The rats used were not at the age corresponding to prostate cancer patients in clinical settings. Our study did not explore CXCL5 blocking in the PRP group. Finally, the main protein quantification results by western blotting were hampered because of small tissue samples. This study provides evidence for the role of CXCL5 and CXCR2 as mediators of PRP effects in the preservation of EF after CN injury. Wu YN, Liao CH, Chen KC, et al. CXCL5 Cytokine Is a Major Factor in Platelet-Rich Plasma's Preservation of Erectile Function in Rats After Bilateral Cavernous Nerve Injury. J Sex Med 2021;XX:XXX-XXX.

The intracavernosal (IC) injection of chitosan activated platelet rich plasma (cPRP) has shown to improve the erectile dysfunction in cavernous nerve injury rat model. However, the action target of PRP in improving neurogenic erectile dysfunction remains unclear. We aimed to determine the effect of cPRP action at early stage that further mediates its effect on erectile function (EF) recovery in the bilateral cavernous nerve crushing (BCNC) injury rat model. Fifty-four rats were randomly divided into two equal groups: intracavernosal ( IC) injection of saline after BCNC (group 1) and IC injection of cPRP after BCNC (group 2). Five animals in each group were euthanized at 3, 7 and 14 day (d) post-injection, and the tissues were harvested to conduct transmission electron microscopy and histological assays. Six animals in each group were used to determine the recovery of EF at 14 and 28 d post-injury. IC injections of cPRP increased all EF parameters at 28 d and 14 d post-injury (p < 0.05). cPRP injections simultaneously prevented the loss of neuronal nitric oxide synthase-positive neurons (p < 0.05) and nerve fibers (p < 0.05) in the major pelvic ganglion and cavernous nerve (CN), respectively, compared with saline injections. This simultaneous accelerated the regeneration of myelinated axons of the CN, reduced apoptosis, and enhanced the proliferation of the corporal smooth muscle cells at an earlier stage. These results suggest that the application of cPRP was beneficial to restore EF via neuroprotective and tissue-protective effects at early stage.

Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.

According to the Taiwan Cancer Report, in 2018, prostate cancer was one of the top five cancers reported in men. Each year, many patients with prostate cancer undergo radical prostatectomy (RP) therapy. One of the most common RP complications is erectile dysfunction (ED). Although consensus guidelines for the management of sexual dysfunction after prostate cancer surgery have been developed for many Western and Asian countries, no such clinical practice guidelines have been developed for Taiwan. The consensus opinions expressed in this article were discussed by numerous experienced physicians in Taiwan, based on both existing international guidelines and their individual experiences with clinical trials and providing advice to clinical physicians on how to inform patients of the risk of ED prior to surgery. This review also discusses how recovery and rehabilitation may be affected by socioeconomic status, the existence of an intimate relationship, comorbidities, or the need for cancer adjuvant therapy and how to determine rehabilitation goals and provide appropriate treatments to assist in the recovery of both short- and long-term sexual function.

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson’s trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications.

This study explored the specific effects of ketamine on bladder function followed by a sequence of histological changes in a rat bladder at fixed time course intervals. The rats were grouped into normal control and experimental animals, and ketamine (100 mg/kg/day) was administrated to the experimental animals for 2, 4, and 8 weeks, respectively; similarly, the control animals received saline. All animals were evaluated for bladder function and histological responses to the treatment. Ultrastructural changes were observed by transmission electron microscopy (TEM). The results showed progressive bladder dysfunctions with hyperactive bladder conditions according to the time course and frequency of exposure to ketamine. Significantly, decreased inter contraction intervals, residual urine volume, peak micturition pressure, and increased micturition frequency were observed. Bladder histology results revealed substantial inflammation and comprehensive submucosa edema in week 2 and 4 rats along with fibrosis and significant bladder detrusor hypertrophy in week 8 rats. TEM analysis revealed bladder wall thickening, deformed blood vessels, detrusor hypertrophy, wobbled gap junction, and barrier dysfunction at different time course levels in experimental animals. These results provided a profound knowledge about the prognosis and step-by-step pathophysiology of the disease, which might help in developing new therapeutic interventions.