Abstract W P102: Predominant Activation of M2 Macrophages by Group-specific Component Protein-derived Macrophage Activating Factor in the Late Phase of Cerebral Ischemia may Contribute to Neurogenesis
Background and Purpose: Peripheral macrophages include M1- and M2 macrophages; they produce pro-inflammatory and anti-inflammatory cytokines, respectively. Inflammation produces group-specific component protein-derived macrophage activating factor (GcMAF). The role of M1- and M2 macrophages activated by GcMAF in the post-ischemic brain remains unclear. We hypothesized that the role of GcMAF after ischemia is time-dependently different and that the dominant activation of M2 macrophages facilitates brain repair.
Methods: After subjecting 7-week-old male Wistar rats to 2-hr middle cerebral artery occlusion they were divided into a group injected for 7 days with GcMAF and a group serving as the vehicle control in the early- and late phase after ischemia induction.
Results: Within 3 days of post-ischemia, the predominant increase in M1 macrophages was associated with expanded ischemic brain damage that was exacerbated by GcMAF. At the 7th post-ischemic day the infarct size was stabilized and M1 macrophages were decreased, although the higher expression in M1- than M2 macrophages persisted. Interestingly, GcMAF treatment from this point cleaned the infarct area, which was associated with phagocytosis via a predominant increase in microglia and M2 macrophages. The effect of GcMAF was abrogated by macrophage-depleting clodronate liposomes. Furthermore, the increase in M2 macrophages was associated with increased BrdU incorporation and the appearance of survival-related molecules and neurovascular unit, suggesting the promotion of neurogenesis.
Conclusion: The activation of M2 macrophages by GcMAF in the late phase of cerebral ischemia may be associated with brain repair.
Author Disclosures: Y. Kurashiki: None. K.T. Kitazato: None. K. Shimada: None. K. Yagi: None. Y. Tada: None. T. Kinouchi: None. M. Sumiyoshi: None. T. Miyamoto: None. J. Satomi: None. T. Kageji: None. Y. Uto: None. S. Nagahiro: None.
- © 2015 by American Heart Association, Inc.