Post-treatment with selective β1 adrenoceptor antagonists provides neuroprotection against transient focal ischemia in rats.
We have reported the neuroprotective effects of pre-treatment with beta-adrenoceptor antagonists on the cerebral infarction at 1 and 7 days after focal ischemia in rats. However, the protective effect of post-treatment with beta-adrenoceptor antagonists has not been investigated yet. This study was conducted to evaluate the post-treatment effects of selective beta(1)-adrenoceptor antagonists in the rat focal cerebral ischemia. Halothane anesthetized, normothermic adult male Sprague-Dawley rats were subjected to 2h of middle cerebral artery occlusion (MCAO) using the intraluminal suture technique confirmed by laser Doppler flowmetry. Rats received intravenous infusion of saline 0.5 mL/h, esmolol 200 microg/kg/min, or landiolol 50 microg/kg/min (n=8 in each group). Infusion was initiated 30 min after MCAO and continued for 24h. Rats were allowed to survive for 7 days, and the neurological deficit score was evaluated at 1, 4 and 7 days after reperfusion. The brains were removed and stained with triphenyltetrazolium chloride at 7 days after reperfusion. Neurological deficit scores were lower in the rats treated with esmolol or landiolol, compared with saline-treated rats at 1 day as well as 4 and 7 days. The infarct volumes of cortical and striatum were less in the rats receiving beta-adrenoceptor antagonists than in saline-treated rats (P<0.05). The current study indicates that administration of selective beta1-adrenoceptor antagonists after the onset of ischemia also improved neurological and histological outcomes following transient focal cerebral ischemia in rats.
Goyagi
Toru
T
Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine, Akita, Japan. tgoyagi@doc.med.akita-u.ac.jp
Horiguchi
Takashi
T
Nishikawa
Toshiaki
T
Tobe
Yoshitsugu
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D016896:Treatment Outcome; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D009025:Morpholines; D018696:Neuroprotective Agents; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C077049:landiolol; D014508:Urea; C036604:esmolol