Abstract

OSTEOPONTIN IS A NOVEL PLAYER IN ENDOGENOUS NEUROREGENERATION AFTER BCNI Weyne, E.; Matsui, H.; L Hannan, J.; Castiglione, F.; Liu, X.; Van der Aa, F.; J Bivalacqua, T.; Albersen, M. KU Leuven University Hospital, Urology, Belgium; Johns Hopkins, Baltimore, USA; East Carolina University, Greenville, USA; KU Leuven, Belgium Objective: Erectile dysfunction remains a frequent sequela of radical prostatectomy (RP) due to neuropraxia of the cavernous nerves(CNs). Osteopontin is secreted by Schwann cells and shown to promote neuroregeneration following peripheral nerve injury. An explorative micro-array study identified osteopontin as the single most upregulated gene in the major pelvic ganglion (MPG) 48hrs after bilateral CN injury (BCNI). To find a new curative therapy for post-RP ED, we examined gene and protein expression of osteopontin in the MPG after BCNI. Methods: Rats underwent either bilateral crush injury of the CNs (BCNI) or sham surgery (n 1⁄4 5/group). MPGs were harvested at 6h, 12h, 24h, 48h, 7d, and 14d after BCNI and 48h after sham surgery to evaluate gene expression of osteopontin by qPCR. Immunohistochemistry (IHC) (n 1⁄4 3) directed against neurofilament and osteopontin was performed in MPG’s obtained from sham and BCNI rats at 48hrs after surgery. Results:OsteopontinmRNAexpressionwas 10-fold increased 12h and 48hrs after BCNI (p < 0,05) compared to sham animals, which did not persist at later times points (7d,14d). IHCdemonstrated that osteopontin was present in the neuronal cell bodies in theMPG and more extensively in the surrounding glial tissue. Staining against osteopontin was more pronounced in BCNI rats, whereas no intraneuronal staining was seen in sham-operated rats. Conclusion: Early after BCNI, we saw a strong upregulation of osteopontin in the MPG and IHC showed an increased protein expression pattern after BCNI. Therefore, modulation of osteopontin could be advantageous in erectile function recovery after RP. Policy of full disclosure: None.

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