Neuroprotective effects of amiodarone in a mouse model of ischemic stroke
Abstract Background Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythm...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | BMC Anesthesiology |
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| Online Access: | http://link.springer.com/article/10.1186/s12871-017-0459-3 |
| _version_ | 1819055471273705472 |
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| author | Masakazu Kotoda Tadahiko Ishiyama Kazuha Mitsui Sohei Hishiyama Takashi Matsukawa |
| author_facet | Masakazu Kotoda Tadahiko Ishiyama Kazuha Mitsui Sohei Hishiyama Takashi Matsukawa |
| author_sort | Masakazu Kotoda |
| collection | DOAJ |
| description | Abstract Background Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice. Methods Focal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation. Results Amiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9 ± 2.1% hemisphere [mean ± SD] vs. 11.2 ± 1.4%; P < 0.05) and improved functional outcomes: lower asymmetric body swing rates (52 ± 17% vs. 65 ± 18%; P < 0.05) and fewer left turns (7.1 ± 1.2 vs. 8.3 ± 1.2; P < 0.05). In contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The neuroprotective effect of amiodarone pre-treatment was abolished by co-administration of veratrine but not by isoproterenol. Conclusions Amiodarone pre-treatment attenuated ischemic brain injury and improved functional outcomes without affecting heart rhythm and blood pressure. The present results showed that amiodarone pre-treatment has neuroprotective effects, at least in part, via blocking the sodium channels. |
| first_indexed | 2024-12-21T13:08:03Z |
| format | Article |
| id | doaj.art-ae52770fc79442f89194687c44a58ec7 |
| institution | Directory Open Access Journal |
| issn | 1471-2253 |
| language | English |
| last_indexed | 2024-12-21T13:08:03Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
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| series | BMC Anesthesiology |
| spelling | doaj.art-ae52770fc79442f89194687c44a58ec72022-12-21T19:02:58ZengBMCBMC Anesthesiology1471-22532017-12-011711710.1186/s12871-017-0459-3Neuroprotective effects of amiodarone in a mouse model of ischemic strokeMasakazu Kotoda0Tadahiko Ishiyama1Kazuha Mitsui2Sohei Hishiyama3Takashi Matsukawa4Department of Anesthesiology, Faculty of Medicine, University of YamanashiSurgical Center, University of Yamanashi Hospital, University of YamanashiDepartment of Anesthesiology, Faculty of Medicine, University of YamanashiDepartment of Anesthesiology, Faculty of Medicine, University of YamanashiDepartment of Anesthesiology, Faculty of Medicine, University of YamanashiAbstract Background Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice. Methods Focal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation. Results Amiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9 ± 2.1% hemisphere [mean ± SD] vs. 11.2 ± 1.4%; P < 0.05) and improved functional outcomes: lower asymmetric body swing rates (52 ± 17% vs. 65 ± 18%; P < 0.05) and fewer left turns (7.1 ± 1.2 vs. 8.3 ± 1.2; P < 0.05). In contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The neuroprotective effect of amiodarone pre-treatment was abolished by co-administration of veratrine but not by isoproterenol. Conclusions Amiodarone pre-treatment attenuated ischemic brain injury and improved functional outcomes without affecting heart rhythm and blood pressure. The present results showed that amiodarone pre-treatment has neuroprotective effects, at least in part, via blocking the sodium channels.http://link.springer.com/article/10.1186/s12871-017-0459-3AmiodaronePre-treatmentStrokeNeuroprotection |
| spellingShingle | Masakazu Kotoda Tadahiko Ishiyama Kazuha Mitsui Sohei Hishiyama Takashi Matsukawa Neuroprotective effects of amiodarone in a mouse model of ischemic stroke BMC Anesthesiology Amiodarone Pre-treatment Stroke Neuroprotection |
| title | Neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| title_full | Neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| title_fullStr | Neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| title_full_unstemmed | Neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| title_short | Neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| title_sort | neuroprotective effects of amiodarone in a mouse model of ischemic stroke |
| topic | Amiodarone Pre-treatment Stroke Neuroprotection |
| url | http://link.springer.com/article/10.1186/s12871-017-0459-3 |
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