Blockade of adrenoreceptors inhibits the splenic response to stroke.
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 alpha and beta 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 alpha1 receptor blocker, or propranolol, a beta 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 alpha and beta adrenergic receptors.
Ajmo
Craig T
CT
Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Collier
Lisa A
LA
Leonardo
Christopher C
CC
Hall
Aaron A
AA
Green
Suzanne M
SM
Womble
Tracy A
TA
Cuevas
Javier
J
Willing
Alison E
AE
Pennypacker
Keith R
KR
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D016207:Cytokines / Q000378:metabolism; D003714:Denervation / Q000379:methods; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D016207:Cytokines; D011412:Propanolamines; D011941:Receptors, Adrenergic; D000077261:Carvedilol; D011433:Propranolol; D014446:Tyrosine 3-Monooxygenase