Metoprolol treatment decreases tissue myeloperoxidase activity after spinal cord injury in rats.
ABSTRACT 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 4h after laminectomy; the trauma only group underwent a 50g/cm contusion injury but received no medication; and three other groups underwent trauma as for the trauma group, and received 30mg/kg methylprednisolone, 1mg/kg metoprolol, or 1mL saline, respectively. All the medications were given intraperitoneally as single doses, immediately after trauma. Spinal cord samples were taken 4h 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.
- SourceAvailable from: Erhan Turkoglu
Dataset: pdf JTN 965
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ABSTRACT: Clinical studies have now confirmed the link between short-term exposure to elevated levels of air pollution and increased cardiovascular mortality, but the mechanisms are complex and not completely elucidated. The present study was designed to investigate the hypothesis that activation of pulmonary sensory receptors and the sympathetic nervous system underlies the influence of pulmonary exposure to diesel exhaust particulate on blood pressure, and on the myocardial response to ischemia and reperfusion.Methods & Results: 6 h after intratracheal instillation of diesel exhaust particulate (0.5 mg), myocardial ischemia and reperfusion was performed in anesthetised rats. Blood pressure, duration of ventricular arrhythmia, arrhythmia-associated death, tissue edema and reperfusion injury were all increased by diesel exhaust particulate exposure. Reperfusion injury was also increased in buffer perfused hearts isolated from rats instilled in vivo, excluding an effect dependent on continuous neurohumoral activation or systemic inflammatory mediators. Myocardial oxidant radical production, tissue apoptosis and necrosis were increased prior to ischemia, in the absence of recruited inflammatory cells. Intratracheal application of an antagonist of the vanilloid receptor TRPV1 (AMG 9810, 30 mg/kg) prevented enhancement of systolic blood pressure and arrhythmia in vivo, as well as basal and reperfusion-induced myocardial injury ex vivo. Systemic beta1 adrenoreceptor antagonism with metoprolol (10 mg/kg) also blocked enhancement of myocardial oxidative stress and reperfusion injury. Pulmonary diesel exhaust particulate increases blood pressure and has a profound adverse effect on the myocardium, resulting in tissue damage, but also increases vulnerability to ischemia-associated arrhythmia and reperfusion injury. These effects are mediated through activation of pulmonary TRPV1, the sympathetic nervous system and locally generated oxidative stress.Particle and Fibre Toxicology 02/2014; 11(1):12. · 6.99 Impact Factor
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ABSTRACT: Throughout the body, the extracellular matrix (ECM) provides structure and organization to tissues and also helps regulate cell migration and intercellular communication. In the injured spinal cord (or brain), changes in the composition and structure of the ECM undoubtedly contribute to regeneration failure. Less appreciated is how the native and injured ECM influences intraspinal inflammation and, conversely, how neuroinflammation affects the synthesis and deposition of ECM after CNS injury. In all tissues, inflammation can be initiated and propagated by ECM disruption. Molecules of ECM newly liberated by injury or inflammation include hyaluronan fragments, tenascins, and sulfated proteoglycans. These act as “damage-associated molecular patterns” or “alarmins”, i.e., endogenous proteins that trigger and subsequently amplify inflammation. Activated inflammatory cells, in turn, further damage the ECM by releasing degradative enzymes including matrix metalloproteinases (MMPs). After spinal cord injury (SCI), destabilization or alteration of the structural and chemical compositions of the ECM affects migration, communication, and survival of all cells – neural and non-neural – that are critical for spinal cord repair. By stabilizing ECM structure or modifying their ability to trigger the degradative effects of inflammation, it may be possible to create an environment that is more conducive to tissue repair and axon plasticity after SCI.Experimental Neurology 08/2014; 258. · 4.62 Impact Factor