{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gao T"],"funding":["Alzheimer’s Association","NIA NIH HHS","Georgia Clinical & Translational Science Alliance of the NIH","NINDS NIH HHS","NIH","Georgia Clinical &amp; Translational Science Alliance of the NIH","Alzheimer's Association","VA MERIT Award","NIH HHS"],"pagination":["116"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6545199"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(1)"],"pubmed_abstract":["<h4>Background</h4>Microglia and CNS-infiltrating monocytes/macrophages (CNS-MPs) perform pro-inflammatory and protective anti-inflammatory functions following ischemic stroke. Selective inhibition of pro-inflammatory responses can be achieved by Kv1.3 channel blockade, resulting in a lower infarct size in the transient middle cerebral artery occlusion (tMCAO) model. Whether beneficial effects of Kv1.3 blockers are mediated by targeting microglia or CNS-infiltrating monocytes/macrophages remains unclear.<h4>Methods</h4>In the 30-min tMCAO mouse model, we profiled functional cell-surface Kv1.3 channels and phagocytic properties of acutely isolated CNS-MPs at various timepoints post-reperfusion. Kv1.3 channels were flow cytometrically detected using fluorescein-conjugated Kv1.3-binding peptide ShK-F6CA as well as by immunohistochemistry. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was performed to measure Kv1.3 (Kcna3) and Kir2.1 (Kcnj2) gene expression. Phagocytosis of 1-μm microspheres by acutely isolated CNS-MPs was measured by flow cytometry.<h4>Results</h4>In flow cytometric assays, Kv1.3 channel expression by CD11b<sup>+</sup> CNS-MPs was increased between 24 and 72 h post-tMCAO and decreased by 7 days post-tMCAO. Increased Kv1.3 expression was restricted to CD11b<sup>+</sup>CD45<sup>low</sup>Ly6c<sup>low</sup> (microglia) and CD11b<sup>+</sup>CD45<sup>high</sup>Ly6C<sup>low</sup> CNS-MPs but not CD11b<sup>+</sup>CD45<sup>high</sup>Ly6c<sup>high</sup> inflammatory monocytes/macrophages. In immunohistochemical studies, Kv1.3 protein expression was increased in Iba1<sup>+</sup> microglia at 24-48 h post-tMCAO. No change in Kv1.3 mRNA in CNS-MPs was observed following tMCAO.<h4>Conclusions</h4>We conclude that resident microglia and a subset of CD45<sup>high</sup>Ly6c<sup>low</sup> CNS-MPs are the likely cellular targets of Kv1.3 blockers and the delayed phase of neuroinflammation is the optimal therapeutic window for Kv1.3 blockade in ischemic stroke."],"journal":["Journal of neuroinflammation"],"pubmed_title":["Temporal profiling of Kv1.3 channel expression in brain mononuclear phagocytes following ischemic stroke."],"pmcid":["PMC6545199"],"funding_grant_id":["K08 NS099474","AARG 37102","K08-NS099474-1","NS-091201","P50 AG025688","UL1TR002378","P51 OD011132","NS-079331","IO1BX003441"],"pubmed_authors":["Raza SA","Yepes M","Rangaraju S","Nwabueze NV","Xiao H","Cheng L","Ramesha S","Tomkins AJ","Gao T"],"additional_accession":[]},"is_claimable":false,"name":"Temporal profiling of Kv1.3 channel expression in brain mononuclear phagocytes following ischemic stroke.","description":"<h4>Background</h4>Microglia and CNS-infiltrating monocytes/macrophages (CNS-MPs) perform pro-inflammatory and protective anti-inflammatory functions following ischemic stroke. Selective inhibition of pro-inflammatory responses can be achieved by Kv1.3 channel blockade, resulting in a lower infarct size in the transient middle cerebral artery occlusion (tMCAO) model. Whether beneficial effects of Kv1.3 blockers are mediated by targeting microglia or CNS-infiltrating monocytes/macrophages remains unclear.<h4>Methods</h4>In the 30-min tMCAO mouse model, we profiled functional cell-surface Kv1.3 channels and phagocytic properties of acutely isolated CNS-MPs at various timepoints post-reperfusion. Kv1.3 channels were flow cytometrically detected using fluorescein-conjugated Kv1.3-binding peptide ShK-F6CA as well as by immunohistochemistry. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was performed to measure Kv1.3 (Kcna3) and Kir2.1 (Kcnj2) gene expression. Phagocytosis of 1-μm microspheres by acutely isolated CNS-MPs was measured by flow cytometry.<h4>Results</h4>In flow cytometric assays, Kv1.3 channel expression by CD11b<sup>+</sup> CNS-MPs was increased between 24 and 72 h post-tMCAO and decreased by 7 days post-tMCAO. Increased Kv1.3 expression was restricted to CD11b<sup>+</sup>CD45<sup>low</sup>Ly6c<sup>low</sup> (microglia) and CD11b<sup>+</sup>CD45<sup>high</sup>Ly6C<sup>low</sup> CNS-MPs but not CD11b<sup>+</sup>CD45<sup>high</sup>Ly6c<sup>high</sup> inflammatory monocytes/macrophages. In immunohistochemical studies, Kv1.3 protein expression was increased in Iba1<sup>+</sup> microglia at 24-48 h post-tMCAO. No change in Kv1.3 mRNA in CNS-MPs was observed following tMCAO.<h4>Conclusions</h4>We conclude that resident microglia and a subset of CD45<sup>high</sup>Ly6c<sup>low</sup> CNS-MPs are the likely cellular targets of Kv1.3 blockers and the delayed phase of neuroinflammation is the optimal therapeutic window for Kv1.3 blockade in ischemic stroke.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2025-04-04T18:59:05.508Z","creation":"2019-07-24T07:08:06Z"},"accession":"S-EPMC6545199","cross_references":{"pubmed":["31153377"],"doi":["10.1186/s12974-019-1510-8"]}}