Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats

Neutrophil infiltration has been reported to play an important role in spinal cord injury (SCI). In addition to their cardioprotective effects, beta-blockers have been found to have neuroprotective effects on the central nervous system, but their effect on SCI has not yet been studied. In the current study, we investigated the effect of metoprolol on myeloperoxidase (MPO) activity, a marker of neutrophil activation, in the spinal cord after experimental SCI in rats. Rats were divided into six groups: controls received only laminectomy and spinal cord samples were taken immediately; the sham operated group received laminectomy, and spinal cord samples were taken 4 h after laminectomy; the trauma only group underwent a 50 g/cm contusion injury but received no medication; and three other groups underwent trauma as for the trauma group, and received 30 mg/kg methylprednisolone, 1 mg/kg metoprolol, or 1 mL saline, respectively. All the medications were given intraperitoneally as single doses, immediately after trauma. Spinal cord samples were taken 4 h after trauma and studied for MPO activity. The results showed that tissue MPO activity increased after injury. Both metoprolol and methylprednisolone treatments decreased MPO activity, indicating a reduction in neutrophil infiltration in damaged tissue. The effect of metoprolol on MPO activity was found to be similar to methylprednisolone. In view of these data, we conclude that metoprolol may be effective in protecting rat spinal cord from secondary injury. (c) 2006 Published by Elsevier Ltd

Neutrophil stunning by metoprolol reduces infarct size

The beta 1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.European Regional Development Fund (ERDF/FEDER) PI10/02268 PI13/01979 RD12/0042/0054ERDF/FEDER SAF2015-65607-RFundacio La Marato-TV3 120/C/2015-20153032Severo Ochoa Center of Excellence (MINECO) SEV-2015-0505Pro-CNIC FoundationSpanish Ministry of Economy and Competitiveness (MINECO)Fundacion Interhospitalaria de Investigacion Cardiovascular (FIC)12.353 JCR (2017) Q1, 3/64 Multidisciplinary SciencesUE

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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