Abstract
Macrophages are crucial for neuroinflammatory responses following traumatic brain injury (TBI), encompassing various subtypes, such as border-associated macrophages (BAMs) that contribute to both brain damage and repair. However, the pathophysiological relevance of subtype-specific molecular markers is poorly understood. This study investigated the role of the BAM marker mannose receptor C-type 1 (MRC1, also known as CD206) during the early phase of TBI using controlled cortical impact (CCI). MRC1 gene expression was up-regulated, peaking between 3 to 7 days post-injury (dpi), and MRC1 protein expression predominantly localized to BAMs. To assess pathophysiological relevance, MRC1-deficient (MRC1-KO) and wild-type littermates (MRC1-WT) were examined following CCI for early neurological deficits, brain structural damage, intracerebral hematoma, and neuroinflammatory marker expression. At 5 dpi, MRC1-KO mice showed increased brain lesion volume and hippocampal neuron loss, with minor differences in neurological deficits compared to MRC1-WT mice. Intracerebral hematoma size increased in male but remained unchanged in female MRC1-KO mice. Immunostaining revealed no genotype-specific effects on GFAP(+) astrocytes, while the number of perilesional CD68(+) macrophages/microglia were reduced in MRC1-KO mice. Analysis of neuroinflammatory gene markers revealed an overall reduction in MRC1-KO mice. Sex-specific regulation was observed for the M2-like macrophage/microglia marker Arg1, with decreased expression in male and increased expression in female MRC1-KO compared to MRC1-WT mice. In conclusion, lack of MRC1 exacerbated brain tissue damage following experimental TBI. Reduced CD68+ macrophages/microglia and neuroinflammatory marker expression suggests impaired neuroinflammatory response in MRC1-KO, indicating MRC1 expression on BAMs contributes to beneficial early neuroinflammatory response following TBI.