Pro-Inflammatory Mediators and Apoptosis Correlate to rt-PA Response in a Novel Mouse Model of Thromboembolic Stroke
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{"title"=>"Pro-inflammatory mediators and apoptosis correlate to rt-PA response in a novel mouse model of thromboembolic stroke", "type"=>"journal", "authors"=>[{"first_name"=>"Saema", "last_name"=>"Ansar", "scopus_author_id"=>"23033396900"}, {"first_name"=>"Eva", "last_name"=>"Chatzikonstantinou", "scopus_author_id"=>"56255144700"}, {"first_name"=>"Rushani", "last_name"=>"Thiagarajah", "scopus_author_id"=>"56805053700"}, {"first_name"=>"Laurent", "last_name"=>"Tritschler", "scopus_author_id"=>"6603483201"}, {"first_name"=>"Marc", "last_name"=>"Fatar", "scopus_author_id"=>"6602687348"}, {"first_name"=>"Michael G.", "last_name"=>"Hennerici", "scopus_author_id"=>"7101760206"}, {"first_name"=>"Stephen", "last_name"=>"Meairs", "scopus_author_id"=>"6701357049"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"372852969", "doi"=>"10.1371/journal.pone.0085849", "pmid"=>"24465746", "issn"=>"19326203", "sgr"=>"84919735045", "scopus"=>"2-s2.0-84919735045"}, "id"=>"2c38829c-0a41-3f37-a863-2bbaad9cc56a", "abstract"=>"BACKGROUND: A recent study suggests that patients with persistent occlusion of the middle cerebral artery (MCA) following treatment with recombinant tissue plasminogen activator (rt-PA) have better outcomes than patients with MCA occlusion not receiving rt-PA. We performed a study to elucidate possible mechanisms of this finding in a new model of thromboembolic stroke closely mimicking human pathophysiology.\\n\\nMETHODS: Thromboembolic stroke was induced by local injection of thrombin directly into the right MCA of C57 black/6J mice. Rt-PA was administered 20 and 40 min after clot formation. The efficiency of rt-PA to induce thrombolysis was measured by laser Doppler. After 24 h, all animals were euthanized and interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP)-9, Caspase-3, hsp 32 and hsp 70 protein levels were investigated by immunofluorescence. Presence of hemorrhage was verified and infarct volume was measured using histology.\\n\\nRESULTS: Thrombin injection resulted in clot formation giving rise to cortical brain infarction. Early rt-PA treatment starting at 20 min after the clot formation resulted in 100% recanalization. However, rt-PA-induced thrombolysis dissolved the clot in only 38% of the animals when administered 40 min after clot formation. Protein levels of IL-6, TNF-α, MMP-9, Caspase-3, hsp 32 and hsp 70 were increased after MCAO, whereas treatment with rt-PA attenuated the expressions of inflammatory markers in those animals where the thrombolysis was successful. In addition, the infarct size was significantly reduced with rt-PA treatment compared to non-treated MCAO, regardless of whether MCA thrombolysis was successful.\\n\\nCONCLUSIONS: The present study demonstrates a clear correlation of the protein expression of inflammatory mediators, apoptosis and stress genes with the recanalization data after rt-PA treatment. In this model rt-PA treatment decreases the infarct size regardless of whether vessel recanalization is successful.", "link"=>"http://www.mendeley.com/research/proinflammatory-mediators-apoptosis-correlate-rtpa-response-novel-mouse-model-thromboembolic-stroke", "reader_count"=>11, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Doctoral Student"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Librarian"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Doctoral Student"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1352019"], "description"=>"<p>Sections from the infarction core showing IL-6, TNF-α, Caspase 3, MMP-9, and hsp 70 protein expressions. The images represent the control group (A, D, G, J, M and P), MCAO (B, E, H, K, N, Q) and MCAO+rt-PA treatment (C, F, I, L, O, R). There are significant increases in IL-6, TNF-α, Caspase 3 and hsp 70 protein levels in the MCAO group compared to the control group. Treatment with rt-PA prevented the increase in expression of these proteins in those animals that recanalized after treatment. There was a slight increase in hsp 32 and MMP-9 protein expression in ischemic brain tissue as compared to control. Data were obtained with confocal microscopy.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Recombinant proteins", "histology", "immunology", "Immunologic techniques", "Immunohistochemical analysis", "Model organisms", "Animal models", "mouse", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "radiology", "Diagnostic radiology", "Magnetic resonance imaging", "rt-pa"], "article_id"=>904658, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Saema Ansar", "Eva Chatzikonstantinou", "Rushani Thiagarajah", "Laurent Tritschler", "Marc Fatar", "Michael G. Hennerici", "Stephen Meairs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085849.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_administration_of_rt_PA_on_protein_expression_/904658", "title"=>"Effect of administration of rt-PA on protein expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:47:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352013"], "description"=>"<p>T2-weighted images (c) and ADC-maps (d) demonstrating infarction.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Recombinant proteins", "histology", "immunology", "Immunologic techniques", "Immunohistochemical analysis", "Model organisms", "Animal models", "mouse", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "radiology", "Diagnostic radiology", "Magnetic resonance imaging", "mr", "angiography", "mca", "occlusion"], "article_id"=>904652, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Saema Ansar", "Eva Chatzikonstantinou", "Rushani Thiagarajah", "Laurent Tritschler", "Marc Fatar", "Michael G. Hennerici", "Stephen Meairs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085849.g001", "stats"=>{"downloads"=>0, "page_views"=>41, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_High_resolution_MR_angiography_of_mouse_brain_before_a_and_after_b_right_MCA_occlusion_arrows_/904652", "title"=>"High resolution MR angiography of mouse brain before (a) and after (b) right MCA occlusion (arrows).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:47:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352014"], "description"=>"<p>(a), MCAO+rt-PA after 20 min and 40 min, (b), MCAO+rt-PA after 40 min. Data were obtained by laser Doppler flowmetry and are expressed as mean ± s.e.m. values, n = 5–9 *P≤0.05, **P≤0.01, ***P<0.001 significant difference between treated groups and MCAO groups. Statistical analyses were performed using Kruskal-Wallis non-parametric test together with Dunn’s post-hoc test.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Recombinant proteins", "histology", "immunology", "Immunologic techniques", "Immunohistochemical analysis", "Model organisms", "Animal models", "mouse", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "radiology", "Diagnostic radiology", "Magnetic resonance imaging", "rt-pa", "cbf", "mcao"], "article_id"=>904653, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Saema Ansar", "Eva Chatzikonstantinou", "Rushani Thiagarajah", "Laurent Tritschler", "Marc Fatar", "Michael G. Hennerici", "Stephen Meairs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085849.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_treatment_with_rt_PA_on_CBF_after_MCAO_in_mice_/904653", "title"=>"Effect of treatment with rt-PA on CBF after MCAO in mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:47:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352015"], "description"=>"<p>Treatment with rt-PA significantly reduced the infarct volume compared to MCAO. Data are expressed as mean± s.e.m.; n = 5–9 *P≤0.05, significant difference between treated groups and MCAO groups. Statistical analyses were performed using Kruskal-Wallis non-parametric test together with Dunn’s post-hoc test.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Recombinant proteins", "histology", "immunology", "Immunologic techniques", "Immunohistochemical analysis", "Model organisms", "Animal models", "mouse", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "radiology", "Diagnostic radiology", "Magnetic resonance imaging", "infarct"], "article_id"=>904654, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Saema Ansar", "Eva Chatzikonstantinou", "Rushani Thiagarajah", "Laurent Tritschler", "Marc Fatar", "Michael G. Hennerici", "Stephen Meairs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085849.g003", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Size_of_infarct_volume_/904654", "title"=>"Size of infarct volume.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:47:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352022"], "description"=>"<p>Data are presented as the mean percentage relative to control ± s.e.m.; n 5 = 9 *P≤0.05, significant difference between control groups and MCAO, # P≤0.05, significant difference between treated groups and MCAO groups. Statistical analyses were performed using Kruskal-Wallis non-parametric test together with Dunn’s post-hoc test.</p>", "links"=>[], "tags"=>["Biochemistry", "proteins", "Recombinant proteins", "histology", "immunology", "Immunologic techniques", "Immunohistochemical analysis", "Model organisms", "Animal models", "mouse", "neurology", "Cerebrovascular diseases", "Ischemic stroke", "radiology", "Diagnostic radiology", "Magnetic resonance imaging", "graphs", "semi-quantification", "fluorescence", "caspase", "hsp", "70", "32"], "article_id"=>904661, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Saema Ansar", "Eva Chatzikonstantinou", "Rushani Thiagarajah", "Laurent Tritschler", "Marc Fatar", "Michael G. Hennerici", "Stephen Meairs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0085849.g005", "stats"=>{"downloads"=>6, "page_views"=>102, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bar_graphs_showing_semi_quantification_of_fluorescence_intensity_for_IL_6_TNF_945_Caspase_3_MMP_9_hsp_70_and_hsp_32_proteins_/904661", "title"=>"Bar graphs showing semi-quantification of fluorescence intensity for IL-6, TNF-α, Caspase 3, MMP-9, hsp 70 and hsp 32 proteins.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:47:34"}

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