{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:40:36Z","timestamp":1792611636321,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Parenchymal border macrophages (PBMs) reside at the interface between the central nervous system and the periphery. They are known to mediate the accessibility of the substances to the brain. However, no one has examined their role in poststroke A\u03b2 (amyloid-\u03b2) clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Permanent focal cerebral ischemia was induced in 8- to 10-week-old C57\/Bl6 male mice by distal middle cerebral artery occlusion. The clodronate liposomes were administered into the cerebral spinal fluid at 7 days before stroke to deplete the PBM population. Sensorimotor and cognitive functions, glymphatic system, and A\u03b2 accumulation were assessed for up to 34 days after stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>The A\u03b2 accumulated along brain blood vessels after stroke in both the ipsilateral and contralateral hemispheres. When PBMs were depleted, glymphatic drainage of A\u03b2 was markedly reduced, and this was accompanied by deterioration of cognitive function, highlighting a critical role for PBMs in poststroke A\u03b2 disposal. A possible mechanism relates to MANF (mesencephalic astrocyte-derived neurotrophic factor). MANF derived from PBMs suppressed astrocytic stress and maintained glymphatic drainage when supplemented into the cerebral spinal fluid. In the chronic phase of stroke, MANF production in PBMs was downregulated, and consequently, glymphatic impairments were exacerbated, which led to ongoing A\u03b2 accumulation and cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In summary, supplementation of MANF not only mitigates the adverse impacts of PBM depletion but also exerts therapeutic effects that improve glymphatic system function. We thus propose that this represents a promising strategy to prevent poststroke cognitive impairment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.124.050266","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T05:04:25Z","timestamp":1747717465000},"page":"2695-2706","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Novel Perivascular Macrophage Mechanism to Promote Glymphatic A\u03b2 Clearance After Stroke"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5843-9882","authenticated-orcid":true,"given":"Chunyi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L., T.L., M.H., X.K., X.S., S.W., D.L., S.S., H.H., X.D., Y.L., Z.L., W.C.)."},{"name":"Department of Cerebrovascular Disease, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China (C.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiemei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L., T.L., M.H., X.K., X.S., S.W., D.L., S.S., H.H., X.D., Y.L., Z.L., W.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3501-028X","authenticated-orcid":true,"given":"Mengyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (C.L., T.L., M.H., X.K., X.S., S.W., D.L., S.S., H.H., X.D., Y.L., Z.L., 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