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Macrophages are comprised of resident brain microglia not infiltrating peripheral monocytes acutely after neonatal stroke
Author(s) -
Denker Sheryl P.,
Ji Shaoquan,
Dingman Andra,
Lee Sarah Y.,
Derugin Nikita,
Wendland Michael F.,
Vexler Zinaida S.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04162.x
Subject(s) - microglia , chemokine , monocyte , medicine , cytokine , immunology , population , pathology , integrin alpha m , flow cytometry , inflammation , macrophage inflammatory protein , infiltration (hvac) , biology , physics , environmental health , thermodynamics
Macrophages can be both beneficial and detrimental after CNS injury. We previously showed rapid accumulation of macrophages in injured immature brain acutely after ischemia‐reperfusion. To determine whether these macrophages are microglia or invading monocytes, we subjected post‐natal day 7 (P7) rats to transient 3 h middle cerebral artery (MCA) occlusion and used flow cytometry at 24 and 48 h post‐reperfusion to distinguish invading monocytes (CD45high/CD11b+) from microglia (CD45low/medium/CD11b+). Inflammatory cytokines and chemokines were determined in plasma, injured and contralateral tissue 1–24 h post‐reperfusion using ELISA‐based cytokine multiplex assays . At 24 h, the number of CD45+/CD11b+ cells increased 3‐fold in injured compared to uninjured brain tissue and CD45 expression shifted from low to medium with less than 10% of the population expressing CD45high. MCA occlusion induced rapid and transient asynchronous increases in the pro‐inflammatory cytokine IL‐β and chemokines cytokine‐induced neutrophil chemoattractant protein 1 (CINC‐1) and monocyte‐chemoattractant protein 1 (MCP‐1), first in systemic circulation and then in injured brain. Double immunofluorescence with cell‐type specific markers showed that multiple cell types in the injured brain produce MCP‐1. Our findings show that despite profound increases in MCP‐1 in injured regions, monocyte infiltration is low and the majority of macrophages in acutely injured regions are microglia.