Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice

Macrophages are involved in demyelination in many brain diseases. However, the role of macrophages in the recovery phase of the ischemic brain is unknown. The present study aims to explore the role of macrophages in the ischemic brain injury and tissue repair following a 90-min transient middle cerebral artery occlusion in mice.

Clodronate liposomes were injected into mice to deplete periphery macrophages. These mice subsequently underwent middle cerebral artery occlusion. F4/80(+) and CD68(+) cells were examined in the mouse spleen and brain to confirm macrophage depletion at 14 days after middle cerebral artery occlusion. Modified neurological severity scores were used to evaluate the behavioral function between 1 and 14 days after middle cerebral artery occlusion. MBP, Iba1, and CD31 immunostaining were performed to determine myelin lesion, microglia activation, and microvessel density.

Clodronate liposomes depleted 80 % of the macrophages in the mouse spleen and reduced macrophage infiltration in the mouse brain. Macrophage depletion reduced the myelin damage in the ipsilateral striatum and microglia activation in both the ipsilateral cortex and striatum, enhanced the microvessel density in the peri-infarct region, attenuated brain atrophy, and promoted neurological recovery following middle cerebral artery occlusion.

Our results suggested that macrophage depletion is a potential intervention that can promote tissue repair and remodeling after brain ischemia, reduce demyelination and microglia activation, and enhance focal microvessel density.