Blockade of adrenoreceptors inhibits the splenic response to stroke

• Published in: Experimental neurology Vol. 218; no. 1; pp. 47 - 55
• Main Authors: Ajmo, Craig T., Collier, Lisa A., Leonardo, Christopher C., Hall, Aaron A., Green, Suzanne M., Womble, Tracy A., Cuevas, Javier, Willing, Alison E., Pennypacker, Keith R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2009; Elsevier
• Subjects: Adrenergic alpha-Antagonists; Adrenergic Antagonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animals; Biological and medical sciences; Carbazoles - pharmacology; Cytokines - metabolism; Denervation - methods; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Fetal Blood - cytology; Flow Cytometry - methods; Humans; Infarction, Middle Cerebral Artery - pathology; Male; Medical sciences; Neurology; Propanolamines - pharmacology; Propranolol - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic - metabolism; Spleen - drug effects; Spleen - immunology; Spleen - pathology; Tyrosine 3-Monooxygenase - genetics; Tyrosine 3-Monooxygenase - metabolism; Vascular diseases and vascular malformations of the nervous system; Vascular disease; Stroke; Nervous system diseases; Central nervous system disease; Cardiovascular disease; Cerebrovascular disease; Cerebral disorder
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2009.03.044

Recent studies have highlighted the involvement of the peripheral immune system in delayed cellular degeneration after stroke. In the permanent middle cerebral artery occlusion (MCAO) model of stroke, the spleen decreases in size. This reduction occurs through the release of splenic immune cells. Systemic treatment with human umbilical cord blood cells (HUCBC) 24 h post-stroke blocks the reduction in spleen size while significantly reducing infarct volume. Splenectomy 2 weeks prior to MCAO also reduces infarct volume, further demonstrating the detrimental role of this organ in stroke-induced neurodegeneration. Activation of the sympathetic nervous system after MCAO results in elevated catecholamine levels both at the level of the spleen, through direct splenic innervation, and throughout the systemic circulation upon release from the adrenal medulla. These catecholamines bind to splenic α and β adrenoreceptors. This study examines whether catecholamines regulate the splenic response to stroke. Male Sprague–Dawley rats either underwent splenic denervation 2 weeks prior to MCAO or received injections of carvedilol, a pan adrenergic receptor blocker, prazosin, an α1 receptor blocker, or propranolol, a β receptor blocker. Denervation was confirmed by reduced splenic expression of tyrosine hydroxylase. Denervation prior to MCAO did not alter infarct volume or spleen size. Propranolol treatment also had no effects on these outcomes. Treatment with either prazosin or carvedilol prevented the reduction in spleen size, yet only carvedilol significantly reduced infarct volume ( p < 0.05). These results demonstrate that circulating blood borne catecholamines regulate the splenic response to stroke through the activation of both α and β adrenergic receptors.