title: α(2)-adrenoceptors do not mediate neuroprotection in acute ischemic stroke in mice.
abstract: We assessed the neuroprotective potential of α(2)-adrenoceptors in ischemic stroke using mice with targeted deletions of individual α(2)-adrenoceptor subtypes (α(2A)(-/-), α(2B)(-/-), α(2C)(-/-), α(2A/C)(-/-)). The effects of the α(2)-adrenoceptor agonist clonidine were studied in parallel. Focal cerebral ischemia was induced with or without clonidine pretreatment by transient middle cerebral artery occlusion. Neurologic outcome and infarct volumes were evaluated on day 1. Cerebral blood flow (CBF) and mean arterial pressure were determined. α(2)-Adrenoceptor null mice did not display larger infarct volumes compared with wild-type (WT) mice under basal conditions (P>0.05). In line with this finding, pretreatment with clonidine did not protect from ischemic brain damage in WT mice or α(2A)(-/-), α(2B)(-/-), and α(2C)(-/-) mice. Clonidine induced smaller infarct volumes only in α(2A/C)(-/-) mice (P<0.05), but this did not translate into improved neurologic function (P>0.05). Importantly, while clonidine caused a significant decrease in arterial blood pressure in all groups, it had no blood pressure lowering effect in α(2A/C)(-/-) mice, and this correlated with higher CBF and smaller infarct volumes in this group. In summary, we could not demonstrate a neuroprotective function of α(2)-adrenoceptors in focal cerebral ischemia. Careful controlling of physiological parameters relevant for stroke outcome is recommended in experimental stroke studies.
authors.affiliation: Department of Anesthesiology and Critical Care, University Clinics of Würzburg, Würzburg, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Brede
authors.forename: Stefan
authors.initials: S
authors.lastname: Braeuninger
authors.forename: Friederike
authors.initials: F
authors.lastname: Langhauser
authors.forename: Lutz
authors.initials: L
authors.lastname: Hein
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D062507:Claudin-5; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D019012:Integrin beta1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology
chemical_list: D062507:Claudin-5; C491511:Cldn5 protein, mouse; D019012:Integrin beta1; D008565:Membrane Proteins; D018341:Receptors, Adrenergic, alpha-2