Epidermal growth factor alleviates cerebral ischemia-induced brain injury by regulating expression of neutrophil gelatinase-associated lipocalin

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) may be a biomarker candidate for brain injury and a novel therapeutic target in ischemic stroke. Epidermal growth factor (EGF) has protective effects on ischemic injury via activating EGF receptor (EGFR). Whether the protection mechanism of activating EGF-EGFR axis against brain injury is involved in regulating NGAL is still unknown. In the present study, we attempted to explore the expression of NGAL in ischemic brain and the effects of EGF on the NGAL expression in a mouse model of middle cerebral artery occlusion (MCAO). Results suggested that the NGAL expression in ischemic brain was markedly increased after cerebral ischemic damage, and specific NGAL-siRNA can attenuate ischemia-triggered infarct volume and neurological deficit. Then, we found that intracerebroventricular EGF treatment may reduce the level of NGAL in ischemic brain, accompanied by functional improvements. Meanwhile, specific JAK2/STAT3 inhibitor AG490 can reverse EGF-induced reduction of NGAL level. Therefore, the elevated NGAL level in ischemic brain may be an important participant in ischemic brain injury. EGF/EGFR activation ameliorated infarct volume of brain tissues and neurological deficit, and the underlying mechanism is involved in regulating the expression of NGAL via the activation of JAK2/STAT3 pathway.

Keywords: EGF receptor; Epidermal growth factor; Ischemic stroke; JAK2/STAT3 pathway; Neutrophil gelatinase-associated lipocalin.