Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia |
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| Authors: | Hwang In Koo Yoo Ki-Yeon An Sung-Jin Li Hua Lee Choong Hyun Choi Jung Hoon Lee Jae-Yong Lee Bong-Hee Kim Young-Myeong Kwon Young-Guen Won Moo-Ho |
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| Institution: | aDepartment of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul 151-742, South Korea;bDepartment of Anatomy and Neurobiology, and Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon 200-702, South Korea;cDepartment of Biochemistry, College of Medicine, Hallym University, Chuncheon 200-702, South Korea;dInstitute for Systems Medicine, Gil medical Center, Gachon University of Medicine and Science, Inchon 406-799, South Korea;eVascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea;fDepartment of Biochemistry, College of Sciences, Yonsei University, Seoul 120-749, South Korea;gMRC Research Institute, Hallym University, Chuncheon 200-702, South Korea |
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| Abstract: | Although acidosis may be involved in neuronal death, the participation of Na+/H+ exchanger (NHE) in delayed neuronal death in the hippocampal CA1 region induced by transient forebrain ischemia has not been well established. In the present study, we investigated the chronological alterations of NHE1 in the hippocampal CA1 region using a gerbil model after ischemia/reperfusion. In the sham-operated group, NHE1 immunoreactivity was weakly detected in the CA1 region. Two and 3 days after ischemia/reperfusion, NHE1 immunoreactivity was observed in glial components, not in neurons, in the CA1 region. Four days after ischemia/reperfusion, NHE1 immunoreactivity was markedly increased in CA1 pyramidal neurons as well as glial cells. These glial cells were identified as astrocytes based on double immunofluorescence staining. Western blot analysis also showed that NHE protein level in the CA1 region began to increase 2 days after ischemia/reperfusion. The treatment of 10 mg/kg 5-(N-ethyl-N-isopropyl) amiloride, a NHE inhibitor, significantly reduced the ischemia-induced hyperactivity 1day after ischemia/reperfusion. In addition, NHE inhibitor potently protected CA1 pyramidal neurons from ischemic damage, and NHE inhibitor attenuated the activation of astrocytes and microglia in the ischemic CA1 region. In addition, NHE inhibitor treatment blocked Na+/Ca2+ exchanger 1 immunoreactivity in the CA1 region after transient forebrain ischemia. These results suggest that NHE1 may play a role in the delayed death, and the treatment with NHE inhibitor protects neurons from ischemic damage. |
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| Keywords: | Ischemic damage Hippocampus Delayed neuronal death Gliosis Na+/H+ exchanger Na+/Ca2+ exchanger Neuroprotection |
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