Moderate cerebral venous congestion induces rapid cerebral protection via adenosine A1 receptor activation.
Stroke is a devastating complication in cardiovascular surgery, and neuronal damage is worsened by intracranial pressure elevation caused by cerebral venous circulatory disturbances (CVCD). However, we have previously reported that CVCD before cerebral ischemia decreases the infarct area. In the present study, focal cerebral ischemia was induced in spontaneously hypertensive rats by filament insertion through the carotid artery. Rats were divided into the following four groups: sham-operated, mild or severe venous congestion (VC), and DPCPX. The DPCPX group received the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prior to mild VC. Behavior, infarct volume, edema and S-100 protein were evaluated among the four groups. The infarct volume rates in mild VC and severe VC groups were significantly less than that in sham-operated and DPCPX groups. However, the mortality of the severe VC group worsened in a time-dependent manner. We observed a significant decrease in edema in the mild VC group compared to the DPCPX group. Behavioral scores also indicated that the mild VC group had fewer neurological deficits than the other three groups, including the DPCPX group. We were able to induce rapid cerebral protection via adenosine A1 receptor activation by administering an appropriate degree of VC prior to cerebral ischemia produced by middle cerebral artery occlusion. Our work suggests possible mechanisms by which such effective VC may lead to cerebral protection and adenosine A1 receptor activation.
Akaiwa
Keiichi
K
Department of Surgery, Kurume University School of Medicine, Kurume, Japan.
Akashi
Hidetoshi
H
Harada
Hideki
H
Sakashita
Hideki
H
Hiromatsu
Shinichi
S
Kano
Tatsuhiko
T
Aoyagi
Shigeaki
S
D058916:Adenosine A1 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002550:Cerebral Veins; D002560:Cerebrovascular Circulation / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D019194:Ischemic Preconditioning; D007601:Jugular Veins; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D013997:Time Factors; D018924:Vascular Capacitance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*; D014690:Venous Pressure; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine