Abstract TP110: Temporally Characteristic Phenotypes of Microglia and Blood-Derived Macrophage on Neuroinflammatory Responses in Cerebral Ischemia Model Using CX3CR1

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Abstract

Ischemic stroke is a devastating disease, second only to cardiac ischemia as a cause of death worldwide. As the blood supply is insufficient to the brain tissue followed by occlusion of the cerebral artery, molecular cues generated by cerebral ischemia activate the components of innate immunity, promote inflammatory signaling and contribute to tissue damage. Microglia known as an immune cell in the central nervous system (CNS) has functions similar to those of macrophages in the periphery. At the functional point of view, resident microglia (M0) can be polarized by molecular cues: M1 phase microglia and M2 phase microglia. Moreover, blood-brain barrier (BBB) causes the extravasation of blood-derived macrophage. However, the interaction between the microglia and blood-derived macrophage is still unknown.

Methods: we used CX3CR1::EGFP transgenic mice to visualize the microglia and blood-derived monocytes dynamics on neuroinflammatory responses. Also, we used the two-photon microscope technique on neuroinflammatory responses by transient middle cerebral artery occlusion (tMCAO) intravial system, time-dependently.

Results: Our preliminary data showed that it is morphologically possible to distinguish activated microglia and infiltrated monocytes from the resident microglia specifically. In addition, infiltrated blood-derived monocytes and resident microglia showed different polarization patterns by specific markers (Iba1, CD86, CD206, and CD45) in time-dependent manners (n=3 / 6h, 1, 3, 5, 7 days) after tMCAO. Furthermore, we performed the cytokine/chemokine array to evaluate the level of specific cytokine/chemokine on ischemic stroke using the serum and brain tissue. In results, the levels of serum and brain tissue of specific cytokine/chemokine showed different levels in all experimental time courses.

Conclusion: Taken together, the overall data demonstrated that dynamics of microglia and blood-derived macrophage using specific type of transgenic mice could be a novel strategy for regulating the M2 anti-inflammatory microglia phenotype rather than M1 pro-inflammatory microglia and finding the optimal time point of drug treatment attenuating ischemic stroke.

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