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Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats.
Brain Res 2019; 1719:288-296BR

Abstract

Progesterone (P4) exerts long-term neuroprotective effects in animal models of stroke, and P4 receptors play a crucial role in this neuroprotection. However, it currently remains unclear whether the activation of P4 receptors alone is sufficient to exert long-term neuroprotection because P4 exhibits other steroidogenic and GABAergic activities via several of its metabolites. Nestorone is a potent selective P4 receptor agonist without other steroidogenic and GABAergic activities. Therefore, we examined the effects of nestorone in adult male rats subjected to transient middle cerebral artery occlusion (MCAO). The dose-response relationship of nestorone showed that the 6-h post-ischemic administration of 10 μg/kg nestorone resulted in greater reductions in infarct sizes 48 h after MCAO than the other two doses tested (5 and 80 μg/kg), and this dose of nestorone significantly decreased astrocyte activation in the peri-infarct cortical region. Moreover, 10 μg/kg nestorone significantly prevented functional impairments on the 28th and 29th days and slightly reduced infarct size on the 30th day after MCAO. The present results suggest that the activation of P4 receptors alone is sufficient to exert neuroprotection against transient cerebral ischemia in adult male rats; therefore, nestorone is a promising agent in post-stroke treatment due to its potent progestational effects without other steroid-related activities.

Authors+Show Affiliations

Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan. Electronic address: 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. Electronic address: msokabe@med.nagoya-u.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30244019

Citation

Tanaka, Motoki, et al. "Nestorone Exerts Long-term Neuroprotective Effects Against Transient Focal Cerebral Ischemia in Adult Male Rats." Brain Research, vol. 1719, 2019, pp. 288-296.
Tanaka M, Ogaeri T, Samsonov M, et al. Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats. Brain Res. 2019;1719:288-296.
Tanaka, M., Ogaeri, T., Samsonov, M., & Sokabe, M. (2019). Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats. Brain Research, 1719, pp. 288-296. doi:10.1016/j.brainres.2018.09.022.
Tanaka M, et al. Nestorone Exerts Long-term Neuroprotective Effects Against Transient Focal Cerebral Ischemia in Adult Male Rats. Brain Res. 2019 Sep 15;1719:288-296. PubMed PMID: 30244019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats. AU - Tanaka,Motoki, AU - Ogaeri,Takunori, AU - Samsonov,Mikhail, AU - Sokabe,Masahiro, Y1 - 2018/09/20/ PY - 2018/06/15/received PY - 2018/09/18/revised PY - 2018/09/18/accepted PY - 2018/9/24/pubmed PY - 2018/9/24/medline PY - 2018/9/24/entrez KW - Middle cerebral artery occlusion KW - Nestorone KW - Progesterone KW - Progesterone receptor KW - Stroke SP - 288 EP - 296 JF - Brain research JO - Brain Res. VL - 1719 N2 - Progesterone (P4) exerts long-term neuroprotective effects in animal models of stroke, and P4 receptors play a crucial role in this neuroprotection. However, it currently remains unclear whether the activation of P4 receptors alone is sufficient to exert long-term neuroprotection because P4 exhibits other steroidogenic and GABAergic activities via several of its metabolites. Nestorone is a potent selective P4 receptor agonist without other steroidogenic and GABAergic activities. Therefore, we examined the effects of nestorone in adult male rats subjected to transient middle cerebral artery occlusion (MCAO). The dose-response relationship of nestorone showed that the 6-h post-ischemic administration of 10 μg/kg nestorone resulted in greater reductions in infarct sizes 48 h after MCAO than the other two doses tested (5 and 80 μg/kg), and this dose of nestorone significantly decreased astrocyte activation in the peri-infarct cortical region. Moreover, 10 μg/kg nestorone significantly prevented functional impairments on the 28th and 29th days and slightly reduced infarct size on the 30th day after MCAO. The present results suggest that the activation of P4 receptors alone is sufficient to exert neuroprotection against transient cerebral ischemia in adult male rats; therefore, nestorone is a promising agent in post-stroke treatment due to its potent progestational effects without other steroid-related activities. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/30244019/Nestorone_exerts_long-term_neuroprotective_effects_against_transient_focal_cerebral_ischemia_in_adult_male_rats L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(18)30487-6 DB - PRIME DP - Unbound Medicine ER -