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The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats.
Transl Stroke Res. 2019 02; 10(1):67-77.TS

Abstract

Progesterone (P4) exerts potent neuroprotection both in young and aged animal models of stroke. The neuroprotection is likely to be mediated by allopregnanolone (ALLO) metabolized from P4 by 5α-reductase, since the neuroprotection is attenuated by the 5α-reductase inhibitor finasteride, which was done only with young animals though. Thus, we do not know the contribution of ALLO to the P4-induced neuroprotection in aged animals. We examined effects of finasteride on the P4-induced neuroprotection in aged (16-18-month-old) male rats subjected to transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by left middle cerebral artery occlusion (MCAO) and occlusion of the bilateral common carotid arteries. MCAO rats were given an 8 mg/kg P4 6 h after MCAO followed by the same treatment once a day for successive 3 days. Finasteride, a 5α-reductase inhibitor, at 20 mg/kg was intraperitoneally injected 30 min prior to the P4-injections. P4 markedly reduced neuronal damage 72 h after MCAO, and the P4-induced neuroprotection was apparently suppressed by finasteride in the aged animals. However, post-ischemic administration of finasteride alone (20 mg/kg) significantly prevented neuronal damage and the impairment of Rotarod performance after MCAO in aged male rats, but not in young ones. The androgen receptor antagonist flutamide markedly suppressed the neuroprotection of finasteride in the cerebral cortex, but not in the striatum, suggesting the androgen receptor-dependent mechanism of the finasteride-induced neuroprotection in the cerebral cortex. Our findings suggested, for the first time, the potential of finasteride as a therapeutic agent in post-ischemic treatment of strokes in aged population.

Authors+Show Affiliations

Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan. m-tanaka@med.nagoya-u.ac.jp.Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan.R-Pharm, Moscow, 123317, Russia.Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550, Japan. msokabe@med.nagoya-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29574659

Citation

Tanaka, Motoki, et al. "The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats." Translational Stroke Research, vol. 10, no. 1, 2019, pp. 67-77.
Tanaka M, Ogaeri T, Samsonov M, et al. The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats. Transl Stroke Res. 2019;10(1):67-77.
Tanaka, M., Ogaeri, T., Samsonov, M., & Sokabe, M. (2019). The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats. Translational Stroke Research, 10(1), 67-77. https://doi.org/10.1007/s12975-018-0624-0
Tanaka M, et al. The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats. Transl Stroke Res. 2019;10(1):67-77. PubMed PMID: 29574659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats. AU - Tanaka,Motoki, AU - Ogaeri,Takunori, AU - Samsonov,Mikhail, AU - Sokabe,Masahiro, Y1 - 2018/03/25/ PY - 2017/10/23/received PY - 2018/03/14/accepted PY - 2018/01/24/revised PY - 2018/3/27/pubmed PY - 2019/4/16/medline PY - 2018/3/26/entrez KW - 5α-reductase inhibitor KW - Finasteride KW - Middle cerebral artery occlusion KW - Progesterone KW - Stroke SP - 67 EP - 77 JF - Translational stroke research JO - Transl Stroke Res VL - 10 IS - 1 N2 - Progesterone (P4) exerts potent neuroprotection both in young and aged animal models of stroke. The neuroprotection is likely to be mediated by allopregnanolone (ALLO) metabolized from P4 by 5α-reductase, since the neuroprotection is attenuated by the 5α-reductase inhibitor finasteride, which was done only with young animals though. Thus, we do not know the contribution of ALLO to the P4-induced neuroprotection in aged animals. We examined effects of finasteride on the P4-induced neuroprotection in aged (16-18-month-old) male rats subjected to transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by left middle cerebral artery occlusion (MCAO) and occlusion of the bilateral common carotid arteries. MCAO rats were given an 8 mg/kg P4 6 h after MCAO followed by the same treatment once a day for successive 3 days. Finasteride, a 5α-reductase inhibitor, at 20 mg/kg was intraperitoneally injected 30 min prior to the P4-injections. P4 markedly reduced neuronal damage 72 h after MCAO, and the P4-induced neuroprotection was apparently suppressed by finasteride in the aged animals. However, post-ischemic administration of finasteride alone (20 mg/kg) significantly prevented neuronal damage and the impairment of Rotarod performance after MCAO in aged male rats, but not in young ones. The androgen receptor antagonist flutamide markedly suppressed the neuroprotection of finasteride in the cerebral cortex, but not in the striatum, suggesting the androgen receptor-dependent mechanism of the finasteride-induced neuroprotection in the cerebral cortex. Our findings suggested, for the first time, the potential of finasteride as a therapeutic agent in post-ischemic treatment of strokes in aged population. SN - 1868-601X UR - https://www.unboundmedicine.com/medline/citation/29574659/The_5α_Reductase_Inhibitor_Finasteride_Exerts_Neuroprotection_Against_Ischemic_Brain_Injury_in_Aged_Male_Rats_ L2 - https://doi.org/10.1007/s12975-018-0624-0 DB - PRIME DP - Unbound Medicine ER -