Overexpression of IL7R Attenuates Cerebral Ischemia-Reperfusion Injury by Inhibiting Apoptosis.

Abstract

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) represents the most critical pathological event in the evolution of ischemic stroke (IS). Apoptosis is particularly important in CIRI pathophysiology. The interleukin-7 receptor (IL7R) is involved in various disease regulatory mechanisms; however, its specific role during CIRI remains unclear. We investigated the mechanistic function of IL7R in CIRI through a mouse modeland through an astrocyte model. METHODS: C57BL/6 mice were randomly allocated to one of five groups: (1) sham; (2) transient middle cerebral artery occlusion (tMCAO); (3) tMCAO + IL7R treatment; (4) tMCAO + negative control (NC); or (5) tMCAO + IL7R + the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor (LY294002) (= 3-7 per group) to evaluate the role of IL7R in CIRI. Thestudy groups were (1) control; (2) oxygen-glucose deprivation/reoxygenation (OGD/R); (3) OGD/R + IL7R; (4) OGD/R + NC; and (5) OGD/R + IL7R + LY294002 groups. After IL7R overexpression was induced, the resulting changes in infarct volume, neurological score, cell viability, and expression of apoptosis-related proteins were assessed. RESULTS: IL7R overexpression significantly attenuated CIRI-induced apoptosis., this intervention improved neurological function, alleviated cerebral edema, and decreased infarct volume in tMCAO mice., after the overexpression of IL7R, flow cytometry analysis revealed a reduction in apoptosis rates post-OGD/R, whereas transmission electron microscopy revealed fewer morphological alterations associated with apoptosis. In addition, the level of Bcl-2-associated X protein (Bax) and cysteine-dependent aspartate-specific Protease-3 (caspase-3) were decreased, whereas that of B-cell lymphoma-2 (Bcl-2) was increased; these effects were reversed by LY294002. CONCLUSION: Overexpression of IL7R was shown to alleviate CIRI by suppressing apoptosis. These findings indicate IL7R as a novel target for IS treatment.