Exploring the role of Na+\H+ exchanger in neonatal brain injuring following hypoxia-ischemia

Abstract

We investigated the role of Na+/H+ exchanger isoform 1 (NHE-1) in neonatal hypoxia ischemia (HI). HI was induced by unilateral ligation of the left common carotid artery is postnatal day 9 (PN) mice, and subsequent exposure of animals to 8% O2 for 55 minutes (min). A pre-treatment group received a selective and potent NHE-1 inhibitor HOE 642 (0.5 mg/kg, intraperitoneally) 5 min before HI, then at 24 hour (h) and 48 h after HI. A post-treatment group received HOE 642 (0.5 mg/kg) at 10 min, 24 h, and 48 h after HI. Saline injections were used as vehicle controls. Neuronal degeneration in the ipsilateral hippocampus, striatum, and thalamus was identified with Fluoro-Jade C positive staining and loss of microtubule associated protein 2 (MAP2) expression 72 hr after HI. NHE-1 protein was up-regulated in glial fibrillary acidic protein positive reactive astrocytes. In HOE 642-treated brains, the hippocampal structures were better preserved, and displayed less neurodegeneration and a higher level of MAP2 expression. These findings suggest that NHE-1-mediated disruption of ionic homeostasis contributes to striatal and CA1 pyramidal neuronal injury after neonatal HI.