Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats
Mirodenafil is a phosphodiesterase 5 (PDE5) inhibitor with high specificity for its target and good blood-brain barrier permeability. The drug, which is currently used for treatment of erectile dysfunction, reduces Aβ and pTau levels and improves cognitive function in mouse models of Alzheimer'...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neurotherapeutics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878747924001508 |
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| author | Fred Kim Padmanabh Singh Hyunji Jo Tianyang Xi Dong-Keun Song Sae Kwang Ku Jai Jun Choung |
| author_facet | Fred Kim Padmanabh Singh Hyunji Jo Tianyang Xi Dong-Keun Song Sae Kwang Ku Jai Jun Choung |
| author_sort | Fred Kim |
| collection | DOAJ |
| description | Mirodenafil is a phosphodiesterase 5 (PDE5) inhibitor with high specificity for its target and good blood-brain barrier permeability. The drug, which is currently used for treatment of erectile dysfunction, reduces Aβ and pTau levels and improves cognitive function in mouse models of Alzheimer's disease. In the present study, we investigated the effect of mirodenafil in the transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO) models of stroke in rats. Starting 24 h after cerebral artery occlusion, mirodenafil was administered subcutaneously at doses of 0.5, 1, and 2 mg/kg per day for 9 days in the tMCAO model and for 28 days in the pMCAO model. Mirodenafil significantly increased sensorimotor and cognitive recovery of tMCAO and pMCAO rats compared to saline control rats, and significantly decreased the amount of degenerative cells and cleaved caspase-3 and cleaved PARP immunoreactive cells. Effects were seen in a dose-dependent manner up to 1 mg/kg mirodenafil. The benefits of mirodenafil treatment increased with longer treatment duration, and the largest improvements over control were typically observed on the last assessment day. There was no effect of mirodenafil on infarct volume in both tMCAO and pMCAO rats. In an experiment to determine the treatment window for mirodenafil effects, a protective effect was observed when treatment was delayed 72 h after MCAO, although the most improvement was observed with shorter treatment windows. Using pMCAO and tMCAO rat models of stroke, we determined that mirodenafil improves the recovery of sensorimotor and cognitive functions after MCAO and protects cortical cells from apoptosis and degeneration. Greater benefit was observed with longer duration of treatment, and improvement was seen even when treatment was delayed. |
| format | Article |
| id | doaj-art-a018b04db03b4ddda47ec6c8156fd90f |
| institution | Kabale University |
| issn | 1878-7479 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurotherapeutics |
| spelling | doaj-art-a018b04db03b4ddda47ec6c8156fd90f2025-02-01T04:11:51ZengElsevierNeurotherapeutics1878-74792025-01-01221e00463Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in ratsFred Kim0Padmanabh Singh1Hyunji Jo2Tianyang Xi3Dong-Keun Song4Sae Kwang Ku5Jai Jun Choung6AriBio Co. Ltd., Seongnam-si 13535, Republic of KoreaAriBio Co. Ltd., Seongnam-si 13535, Republic of KoreaAriBio Co. Ltd., Seongnam-si 13535, Republic of KoreaAriBio Co. Ltd., Seongnam-si 13535, Republic of KoreaAriBio Co. Ltd., Seongnam-si 13535, Republic of Korea; Corresponding authors.College of Korean Medicine, Daegu Haany University, Gyeongsan-si 38610, Republic of Korea; Corresponding authors.AriBio Co. Ltd., Seongnam-si 13535, Republic of Korea; Corresponding authors.Mirodenafil is a phosphodiesterase 5 (PDE5) inhibitor with high specificity for its target and good blood-brain barrier permeability. The drug, which is currently used for treatment of erectile dysfunction, reduces Aβ and pTau levels and improves cognitive function in mouse models of Alzheimer's disease. In the present study, we investigated the effect of mirodenafil in the transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO) models of stroke in rats. Starting 24 h after cerebral artery occlusion, mirodenafil was administered subcutaneously at doses of 0.5, 1, and 2 mg/kg per day for 9 days in the tMCAO model and for 28 days in the pMCAO model. Mirodenafil significantly increased sensorimotor and cognitive recovery of tMCAO and pMCAO rats compared to saline control rats, and significantly decreased the amount of degenerative cells and cleaved caspase-3 and cleaved PARP immunoreactive cells. Effects were seen in a dose-dependent manner up to 1 mg/kg mirodenafil. The benefits of mirodenafil treatment increased with longer treatment duration, and the largest improvements over control were typically observed on the last assessment day. There was no effect of mirodenafil on infarct volume in both tMCAO and pMCAO rats. In an experiment to determine the treatment window for mirodenafil effects, a protective effect was observed when treatment was delayed 72 h after MCAO, although the most improvement was observed with shorter treatment windows. Using pMCAO and tMCAO rat models of stroke, we determined that mirodenafil improves the recovery of sensorimotor and cognitive functions after MCAO and protects cortical cells from apoptosis and degeneration. Greater benefit was observed with longer duration of treatment, and improvement was seen even when treatment was delayed.http://www.sciencedirect.com/science/article/pii/S1878747924001508Middle cerebral artery occlusion (MCAO)MirodenafilPDE5 inhibitorRatsStroke |
| spellingShingle | Fred Kim Padmanabh Singh Hyunji Jo Tianyang Xi Dong-Keun Song Sae Kwang Ku Jai Jun Choung Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats Neurotherapeutics Middle cerebral artery occlusion (MCAO) Mirodenafil PDE5 inhibitor Rats Stroke |
| title | Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats |
| title_full | Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats |
| title_fullStr | Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats |
| title_full_unstemmed | Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats |
| title_short | Therapeutic effects of mirodenafil, a phosphodiesterase 5 inhibitor, on stroke models in rats |
| title_sort | therapeutic effects of mirodenafil a phosphodiesterase 5 inhibitor on stroke models in rats |
| topic | Middle cerebral artery occlusion (MCAO) Mirodenafil PDE5 inhibitor Rats Stroke |
| url | http://www.sciencedirect.com/science/article/pii/S1878747924001508 |
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