title: Posttreatment but not pretreatment with selective beta-adrenoreceptor 1 antagonists provides neuroprotection in the hippocampus in rats subjected to transient forebrain ischemia.
abstract: BACKGROUND
  beta-Adrenoreceptor antagonists provide neuroprotection against focal cerebral ischemia, but the effects of these antagonists on experimental global cerebral ischemia are unknown. That is, the effect of beta-adrenoreceptor antagonism in vulnerable brain regions after ischemic insult has not been examined. Therefore, we investigated the neuroprotective effects of preischemic or postischemic administration of propranolol (a nonselective beta-adrenoreceptor antagonist), esmolol, and landiolol (selective beta-adrenoreceptor 1 antagonists) against forebrain ischemia in rats.
  
  
  METHODS
  IV administration of saline 10 microL . h(-1), propranolol 100 microg . kg(-1) . min(-1), esmolol 200 microg . kg(-1) . min(-1), or landiolol 50 microg . kg(-1) . min(-1) in male Sprague-Dawley rats was started 30 minutes before or 60 minutes after 8-minute bilateral carotid artery occlusion combined with hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All drugs were administered continuously until 5 days after reperfusion, and the animals were evaluated neurologically and histologically after this 5-day period.
  
  
  RESULTS
  Preischemic treatment with propranolol, esmolol, or landiolol failed to provide neuroprotection against forebrain ischemia in the hippocampus. Rats treated with propranolol tended to have a worse score for motor activity and a higher mortality rate (up to 64%), but the differences with other groups were not statistically significant. Postischemic treatment with esmolol and landiolol, but not with propranolol, reduced neuronal injury after forebrain ischemia. However, motor activity did not differ among rats treated postischemically with any of the beta-adrenoreceptor antagonists or saline.
  
  
  CONCLUSIONS
  Postischemic treatment with esmolol and landiolol provided neuroprotection in the hippocampus in rats subjected to bilateral carotid artery occlusion combined with hemorrhagic shock, whereas treatment with propranolol failed to show neuroprotection. We suggest that concomitant beta-blockade and shock might work as a systemic depressant, rather than a neuroprotectant, resulting in exacerbation of cerebral ischemia.
authors.affiliation: Department of Anesthesiology, Nara Medical University, Nara 634-8522, Japan. seninoue@naramed-u.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Iwata
authors.forename: Satoki
authors.initials: S
authors.lastname: Inoue
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Furuya
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D056344:Executive Function / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D015918:Infusion Pumps, Implantable; D002546:Ischemic Attack, Transient / Q000401:mortality / Q000473:pathology*; D008297:Male; D018696:Neuroprotective Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D018696:Neuroprotective Agents