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Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice.
Paul, Marina; Paul, Jonathan W; Hinwood, Madeleine; Hood, Rebecca J; Martin, Kristy; Abdolhoseini, Mahmoud; Johnson, Sarah J; Pollack, Michael; Nilsson, Michael; Walker, Frederick R.
Afiliação
  • Paul M; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Paul JW; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
  • Hinwood M; Centre for Rehab Innovations, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Hood RJ; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
  • Martin K; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Abdolhoseini M; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
  • Johnson SJ; Centre for Rehab Innovations, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Pollack M; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Nilsson M; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Walker FR; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.
Int J Mol Sci ; 24(14)2023 Jul 20.
Article em En | MEDLINE | ID: mdl-37511466
Clopidogrel, which is one of the most prescribed antiplatelet medications in the world, is given to stroke survivors for the prevention of secondary cardiovascular events. Clopidogrel exerts its antiplatelet activity via antagonism of the P2Y12 receptor (P2RY12). Although not widely known or considered during the initial clinical trials for clopidogrel, P2RY12 is also expressed on microglia, which are the brain's immune cells, where the receptor facilitates chemotactic migration toward sites of cellular damage. If microglial P2RY12 is blocked, microglia lose the ability to migrate to damaged sites and carry out essential repair processes. We aimed to investigate whether administering clopidogrel to mice post-stroke was associated with (i) impaired motor skills and cognitive recovery; (ii) physiological changes, such as survival rate and body weight; (iii) changes in the neurovascular unit, including blood vessels, microglia, and neurons; and (iv) changes in immune cells. Photothrombotic stroke (or sham surgery) was induced in adult male mice. From 24 h post-stroke, mice were treated daily for 14 days with either clopidogrel or a control. Cognitive performance (memory and learning) was assessed using a mouse touchscreen platform (paired associated learning task), while motor impairment was assessed using the cylinder task for paw asymmetry. On day 15, the mice were euthanized and their brains were collected for immunohistochemistry analysis. Clopidogrel administration significantly impaired learning and memory recovery, reduced mouse survival rates, and reduced body weight post-stroke. Furthermore, clopidogrel significantly increased vascular leakage, significantly increased the number and appearance of microglia, and significantly reduced the number of T cells within the peri-infarct region post-stroke. These data suggest that clopidogrel hampers cognitive performance post-stroke. This effect is potentially mediated by an increase in vascular permeability post-stroke, providing a pathway for clopidogrel to access the central nervous system, and thus, interfere in repair and recovery processes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acidente Vascular Cerebral Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Acidente Vascular Cerebral Idioma: En Ano de publicação: 2023 Tipo de documento: Article