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The inhibitor of 20‐HETE synthesis, TS‐011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice
Author(s) -
Marumo Toshiyuki,
Eto Kei,
Wake Hiroaki,
Omura Tomohiro,
Nabekura Junichi
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00973.x
Subject(s) - cerebral blood flow , middle cerebral artery , ischemia , medicine , autoregulation , microcirculation , perfusion , occlusion , anesthesia , cerebral circulation , stroke (engine) , cerebral arteries , cardiology , blood flow , blood pressure , mechanical engineering , engineering
BACKGROUND AND PURPOSE 20‐Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20‐Hydroxyeicosatetraenoic acid synthesis, TS‐011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS‐011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS‐011 on microvessels after cerebral ischaemia. EXPERIMENTAL APPROACH TS‐011 (0.3 mg·kg −1 ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri‐infarct microvessels were measured using in vivo two‐photon imaging. KEY RESULTS The cerebral blood flow velocities in the peri‐infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle‐treated mice. We found that TS‐011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri‐infarct microvessels seen in the vehicle‐treated mice after reperfusion. In addition, TS‐011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle‐treated group. Moreover, TS‐011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. CONCLUSIONS AND IMPLICATIONS These findings demonstrated that infusion of TS‐011 improved defects in the autoregulation of peri‐infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia.