| Autor: |
Pawletko K; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.; Department for Experimental Medicine, Medical University of Silesia, Medyków 4, 40-752 Katowice, Poland., Jędrzejowska-Szypułka H; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland., Bogus K; Department of Histology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland., Pascale A; Department of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy., Fahmideh F; Department of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy., Marchesi N; Department of Drug Sciences, Pharmacology Section, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy., Grajoszek A; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.; Department for Experimental Medicine, Medical University of Silesia, Medyków 4, 40-752 Katowice, Poland., Gendosz de Carrillo D; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.; Department of Histology and Cell Pathology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland., Barski JJ; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.; Department for Experimental Medicine, Medical University of Silesia, Medyków 4, 40-752 Katowice, Poland. |
| Abstrakt: |
Ischemic stroke is the most common cause of adult disability and one of the leading causes of death worldwide, with a serious socio-economic impact. In the present work, we used a new thromboembolic model, recently developed in our lab, to induce focal cerebral ischemic (FCI) stroke in rats without reperfusion. We analyzed selected proteins implicated in the inflammatory response (such as the RNA-binding protein HuR, TNFα, and HSP70) via immunohistochemistry and western blotting techniques. The main goal of the study was to evaluate the beneficial effects of a single administration of minocycline at a low dose (1 mg/kg intravenously administered 10 min after FCI) on the neurons localized in the penumbra area after an ischemic stroke. Furthermore, given the importance of understanding the crosstalk between molecular parameters and motor functions following FCI, motor tests were also performed, such as the Horizontal Runway Elevated test, CatWalk™ XT, and Grip Strength test. Our results indicate that a single administration of a low dose of minocycline increased the viability of neurons and reduced the neurodegeneration caused by ischemia, resulting in a significant reduction in the infarct volume. At the molecular level, minocycline resulted in a reduction in TNFα content coupled with an increase in the levels of both HSP70 and HuR proteins in the penumbra area. Considering that both HSP70 and TNF-α transcripts are targeted by HuR, the obtained results suggest that, following FCI, this RNA-binding protein promotes a protective response by shifting its binding towards HSP70 instead of TNF-α. Most importantly, motor tests showed that reduced inflammation in the brain damaged area after minocycline treatment directly translated into a better motor performance, which is a fundamental outcome when searching for new therapeutic options for clinical practice. |
