Details

Autor(en) / Beteiligte

• Cengiz, Pelin
• Kleman, Neil
• Uluc, Kutluay
• Kendigelen, Pinar
• Hagemann, Tracy
• Akture, Erinc
• Messing, Albee
• Ferrazzano, Peter
• Sun, Dandan

Titel

Inhibition of Na+/H+ exchanger isoform 1 is neuroprotective in neonatal hypoxic ischemic brain injury

Ist Teil von

• Antioxidants & redox signaling, 2011-05, Vol.14 (10), p.1803-1813

Ort / Verlag

United States

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 in postnatal day 9 (P9) mice, and subsequent exposure of animals to 8% O(2) for 55 min. A pre/posttreatment group received a selective and potent NHE-1 inhibitor HOE 642 (0.5 mg/kg, intraperitoneally) 5 min before HI, then at 24 and 48 h after HI. A posttreatment 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. The vehicle-control brains at 72 h after HI exhibited neuronal degeneration in the ipsilateral hippocampus, striatum, and thalamus, as identified with Fluoro-Jade C positive staining and loss of microtubule-associated protein 2 (MAP2) expression. NHE-1 protein was upregulated in glial fibrillary acidic protein-positive reactive astrocytes. In HOE 642-treated brains, the morphologic hippocampal structures were better preserved and displayed less neurodegeneration and a higher level of MAP2 expression. Motor-learning deficit was detected at 4 weeks of age after HI in the vehicle control group. Inhibition of NHE-1 in P9 mice not only reduced neurodegeneration during the acute stage of HI but also improved the striatum-dependent motor learning and spatial learning at 8 weeks of age after HI. These findings suggest that NHE-1-mediated disruption of ionic homeostasis contributes to striatal and CA1 pyramidal neuronal injury after neonatal HI.