Repetitive acute intermittent hypoxia differentially affects CD11b⁺ cell phenotypes after C2 spinal hemisection (713.6)

Abstract

Inflammation is a hallmark of spinal cord injury (SCI), mediated in part by CD11b+ resident microglia (MG) and infiltrating macrophages (MP). Although neuroinflammation is well‐characterized at the lesion site, little is known about MG/MP activities above or below the injury. Repetitive acute intermittent hypoxia (rAIH) elicits somatic motor plasticity following chronic spinal injury, and this plasticity is undermined by neuroinflammation. Since recent microarray data suggest that rAIH (4 weeks) suppresses spinal inflammation, we tested the hypothesis that rAIH shifts the MG/MP phenotype following C2 spinal hemisection (C2HS), decreasing inflammatory (M1) and increasing reparative/trophic (M2) activities. We further posited that these effects would differ above vs. below the injury site. mRNAs for molecular markers of M1 and M2 phenotype were assessed (qRT‐PCR) on immunomagnetically isolated MG/MP from sham‐ and C2HS‐operated rats exposed to normoxia or rAIH (10 episodes per day, 3 x per week, 4 wks) beginning 3 days post‐surgery. In normoxia, whereas M1 genes were unaffected by C2HS above the injury site (brainstem), M2 genes were increased. In contrast, below the injury (C4‐C6), M2 genes were unaffected, and there was little indication of increased M1 expression. Treatment with rAIH decreased both M1 and M2 gene expression in brainstem MG/MP, but increased M2 and decreased M1 gene expression below the injury, suggesting a switch to a supportive phenotype below the injury. Thus, rAIH elicits differential effects on MG/MP activities above and below the injury, and its beneficial effects on spinal plasticity and functional recovery following SCI may involve alterations in CD11b+ cell phenotypes. Grant Funding Source: Supported by NIH R01 HL111598, The Craig H. Neilsen Foundation, and Wisconsin Hilldale Fellowship