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Article

Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death

1
Department of Neurosurgery, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan
2
Department of Surgical Pathology, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan
3
General Education Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo 650-8530, Japan
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Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan
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Department of Therapeutic Progress in Brain Diseases, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo 663-8501, Japan
6
Department of Biomedical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(6), 1374; https://doi.org/10.3390/cells9061374
Received: 2 May 2020 / Revised: 27 May 2020 / Accepted: 29 May 2020 / Published: 1 June 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cerebral Ischemia)
Ischemic stroke is a critical disease caused by cerebral artery occlusion in the central nervous system (CNS). Recent therapeutic advances, such as neuroendovascular intervention and thrombolytic therapy, have allowed recanalization of occluded brain arteries in an increasing number of stroke patients. Although previous studies have focused on rescuing neural cells that still survive despite decreased blood flow, expanding the therapeutic time window may allow more patients to undergo reperfusion in the near future, even after lethal ischemia, which is characterized by death of mature neural cells, such as neurons and glia. However, it remains unclear whether early reperfusion following lethal ischemia results in positive outcomes. The present study used two ischemic mouse models—90-min transient middle cerebral artery occlusion (t-MCAO) paired with reperfusion to induce lethal ischemia and permanent middle cerebral artery occlusion (p-MCAO)—to investigate the effect of early reperfusion up to 8 w following MCAO. Although early reperfusion following 90-min t-MCAO did not rescue mature neural cells, it preserved the vascular cells within the ischemic areas at 1 d following 90-min t-MCAO compared to that following p-MCAO. In addition, early reperfusion facilitated the healing processes, including not only vascular but also neural repair, during acute and chronic periods and improved recovery. Furthermore, compared with p-MCAO, early reperfusion after t-MCAO prevented behavioral symptoms of neurological deficits without increasing negative complications, including hemorrhagic transformation and mortality. These results indicate that early reperfusion provides beneficial effects presumably via cytoprotective and regenerative mechanisms in the CNS, suggesting that it may be useful for stroke patients that experienced lethal ischemia. View Full-Text
Keywords: ischemic stroke; early reperfusion; transient middle cerebral artery occlusion; permanent middle cerebral artery occlusion; central nervous system ischemic stroke; early reperfusion; transient middle cerebral artery occlusion; permanent middle cerebral artery occlusion; central nervous system
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MDPI and ACS Style

Tanaka, Y.; Nakagomi, N.; Doe, N.; Nakano-Doi, A.; Sawano, T.; Takagi, T.; Matsuyama, T.; Yoshimura, S.; Nakagomi, T. Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death. Cells 2020, 9, 1374. https://doi.org/10.3390/cells9061374

AMA Style

Tanaka Y, Nakagomi N, Doe N, Nakano-Doi A, Sawano T, Takagi T, Matsuyama T, Yoshimura S, Nakagomi T. Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death. Cells. 2020; 9(6):1374. https://doi.org/10.3390/cells9061374

Chicago/Turabian Style

Tanaka, Yasue, Nami Nakagomi, Nobutaka Doe, Akiko Nakano-Doi, Toshinori Sawano, Toshinori Takagi, Tomohiro Matsuyama, Shinichi Yoshimura, and Takayuki Nakagomi. 2020. "Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death" Cells 9, no. 6: 1374. https://doi.org/10.3390/cells9061374

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