{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:51Z","timestamp":1790657991776,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Neonatal hypoxic\u2013ischemic encephalopathy (HIE) causes severe neurodevelopmental impairment, but the upstream immune mechanisms that initiate this process remain unclear. We investigated whether mast cell (MC)\u2010derived tryptase contributes to aberrant microglia\u2010mediated synaptic pruning through PAR\u20102\/MAPK\/NF\u2010\u03baB signaling after neonatal hypoxic\u2013ischemic (HI) injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A postnatal Day\u20107 rat HI model was established using the Rice\u2010Vannucci method. MC abundance, c\u2010Kit and tryptase expression, PAR\u20102\/MAPK\/NF\u2010\u03baB signaling, and synaptic integrity were assessed using histological, immunofluorescence, biochemical, ultrastructural, and three\u2010dimensional (3D) reconstruction analyses. Microglia\u2010targeted F2rl1 silencing and pharmacological inhibition with FSLLRY\u2010NH2 or APC366 were used to examine PAR\u20102 and tryptase\u2010related signaling. Complementary oxygen\u2013glucose deprivation\/reperfusion (OGD\/R) experiments were performed in BV\u20102 microglia. Cognitive outcomes were assessed using the Morris water maze and Y maze.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HI increased hippocampal MC abundance and tryptase expression, and these changes were associated with acute neurological deficits. HI insult also increased complement associated synaptic labeling, PAR\u20102\/MAPK\/NF\u2010\u03baB signaling, CD68 expression, and engulfment of PSD95 positive synaptic material. Microglia\u2010targeted F2rl1 silencing attenuated pathway activation and synaptic engulfment. FSLLRY\u2010NH2 and APC366 similarly reduced HI associated signaling and microglial synaptic engulfment, while APC366 preserved dendritic spine density and synaptic ultrastructure and improved long\u2010term spatial learning and memory. In BV\u20102 microglial cells, exogenous tryptase enhanced OGD\/R associated CD68 expression and MAPK\/NF\u2010\u03baB phosphorylation, which were attenuated by F\u2010NH2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MC\u2010derived tryptase is an upstream contributor to pathological microglial synaptic pruning and cognitive impairment after neonatal HI, potentially involving the PAR\u20102\/MAPK\/NF\u2010\u03baB axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71189","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:51:21Z","timestamp":1790657481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mast Cell\u2013Microglia Crosstalk Drives Aberrant Synaptic Pruning Through\n                    <scp>PAR<\/scp>\n                    \u20102\/\n                    <scp>MAPK<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Signaling in Neonatal Hypoxic\u2013Ischemic Encephalopathy"],"prefix":"10.1002","volume":"32","author":[{"given":"Yanping","family":"Yang","sequence":"first","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingliang","family":"Cai","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian 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Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubing","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian University of Traditional Chinese Medicine, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqian","family":"Teng","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjie","family":"Wei","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian 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Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1864-6729","authenticated-orcid":false,"given":"Xiaohui","family":"Chen","sequence":"additional","affiliation":[{"name":"Shengli Clinical Medical College of Fujian Medical University, Department of Anesthesiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"7","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1038\/s41390-025-03986-2","article-title":"Neonatal Encephalopathy and Hypoxic\u2010Ischemic Encephalopathy: The State of the Art","volume":"98","author":"Chakkarapani E.","year":"2025","journal-title":"Pediatric 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