title: Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia.
abstract: Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups (n = 8 in each group): Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine D2 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.
authors.affiliation: Department of Urology, Gachon University Gil Medical Center, Gachon University, Incheon 405-760, Republic of Korea.
authors.forename: Kwang Taek
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Urology, Gachon University Gil Medical Center, Gachon University, Incheon 405-760, Republic of Korea.
authors.forename: Kyung Jin
authors.initials: KJ
authors.lastname: Chung
authors.affiliation: Department of Urology, Gachon University Gil Medical Center, Gachon University, Incheon 405-760, Republic of Korea.
authors.forename: Han Sae
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Il Gyu
authors.initials: IG
authors.lastname: Ko
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Chang Ju
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Urology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon 301-721, Republic of Korea.
authors.forename: Yong Gil
authors.initials: YG
authors.lastname: Na
authors.affiliation: Department of Urology, Gachon University Gil Medical Center, Gachon University, Incheon 405-760, Republic of Korea.
authors.forename: Khae Hawn
authors.initials: KH
authors.lastname: Kim
keywords: Tadalafil; brain injury; cerebral ischemia; cyclic guanosine monophosphate; dopamine; dopamine D2 receptor; grants-supported paper; neural regeneration; neuroregneration; phosphodiesterase type-5 inhibitor; photographs-containing paper