Ischemic neurons recruit natural killer cells that accelerate brain infarction

Project: Research

Investigators

  • Fu-Dong Shi (PI)

Description

Brain ischemia and reperfusion activate the immune system, which may aggravate stroke. The abrupt development of brain ischemic lesions during stroke suggests that innate immune cells may be involved. Natural killer (NK) cells are innate lymphocytes that can be swiftly mobilized during the earliest phases of immune responses but their role during stroke remains unknown. In a mouse model of cerebral ischemia, we found that ischemic neuron-derived fractalkine recruits NK cells, and the infarction volume correlates with the number of infiltrating NK cells. Our data suggest that NK cells may accelerate brain infarction during acute stroke. The major goal of this proposal is to determine the role of NK cells in stroke and dissect cellular and molecular pathways bridging the ischemic neurons and NK cells to explore the feasibility of clinical translation. We hypothesize that NK cells aggravate brain infarction via direct killing of ischemic neuronsand augment local inflammation in stroke. Our specific aims are to: 1) Determine NK cell-mediated aggravation of stroke; 2) Dissect mechanisms of NK cell-mediated aggravation of stroke. The outcome of this proposed project will elucidate the role of NK cells in the mediation of neuronal death in the ischemic brain and potentially provide modulation of NK cells as a novel approach in stroke therapeutics.
Award amount$140,000.00
Award date01/01/2014
Program typeGrant-in-Aid
Award ID14GRNT18970031
Effective start/end date01/01/201412/31/2015
StatusFinished