Effects of mitotempo, a mitochondria targeting agent, in a rat model of spinal cord injury-induced bladder dysfunction

Effects of Mitotempo, a Mitochondria Targeting Agent, in a Rat Model of Spinal Cord Injury-Induced Bladder Dysfunction Spinal cord injury (SCI) is an important health problem affecting millions of people worldwide by reducing duration and quality of life of patients and causing economic and work force losses. Besides locomotor dysfunction, SCI induces somatic and autonomic dysfunctions that negatively affect the patient's quality of life. Urinary bladder dysfunction is a SCI-induced problem that leads to bladder overactivity or areflexia depending on lesion location and type of affected neurons. Currently, understanding SCI-induced pathophysiology and effective treatments is still limited. In recent studies, SCI-induced dysfunctions have been associated with mitochondrial damage and oxidative stress-induced cellular destruction in neurons and other cell types (such as smooth musle, epithelial cells, vascular cells). Therefore, therapeutics targeting mitochondrial mechanisms have attracted great interest, yet the effects of these mechanisms on bladder dysfunction are unknown. "Mitoceuticals" are mitochondria-targeting agents that prevent mitochondrial damage and thus prevent/reduce the effect of SCI on organs. MitoTEMPO, is a neuroprotective antioxidant of this group that has shown promising results on mitochondrial function after SCI and oxidative stress injury. In this thesis study, the therapeutic effect of mitoTEMPO was investigated in a rat SCI-induced bladder dysfunction model. SCI induced bladder dysfunction in rats was induced by compression of the thoracic vertebra at T9 level and 1mg/kg/day mitoTEMPO was administered after the injury. After 3 and 14 days of mitoTEMPO administration, metabolic (body weight, water intake, urine output, fecal output), functional (detrusor muscle contraction and relaxation responses), molecular (Drp1 and Mfn protein expressions) and histopathological (H&E staining; TOM20, Drp1, Mfn2 protein immunohistochemistry) evaluations were performed. In conclusion, functional and cellular improvement was observed in bladder dysfunction developing after SCI with 14-day mitoTEMPO treatment, and partially in 3-day treatment. In this study, mitoTEMPO and similar mitoceutical agents were shown to have therapeutic potential in neurogenic bladder dysfunction. Keywords: Antioxidant, Bladder, Drp1, Mitochondria, Mfn2, Organ Bath, Rat, TOM