Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia

In Koo Hwang, Ki Yeon Yoo, Sung Jin An, Hua Li, Choong Hyun Lee, Jung Hoon Choi, Jae Yong Lee, Bong Hee Lee, Young Myeong Kim, Young-Guen Kwon, Moo Ho Won

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)314-323
Number of pages10
JournalExperimental Neurology
Volume212
Issue number2
DOIs
Publication statusPublished - 2008 Aug 1

Fingerprint

Hippocampal CA1 Region
Sodium-Hydrogen Antiporter
Gerbillinae
Neuroprotective Agents
Ischemia
Reperfusion
Pyramidal Cells
Neuroglia
Prosencephalon
Astrocytes
Neurons
Microglia
Acidosis
Fluorescent Antibody Technique
Therapeutics

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Cite this

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. / Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia. In: Experimental Neurology. 2008 ; Vol. 212, No. 2. pp. 314-323.
@article{c96fe500c49c46649b8ec982d10a5e7b,
title = "Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia",
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.",
author = "Hwang, {In Koo} and Yoo, {Ki Yeon} and An, {Sung Jin} and Hua Li and Lee, {Choong Hyun} and Choi, {Jung Hoon} and Lee, {Jae Yong} and Lee, {Bong Hee} and Kim, {Young Myeong} and Young-Guen Kwon and Won, {Moo Ho}",
year = "2008",
month = "8",
day = "1",
doi = "10.1016/j.expneurol.2008.04.007",
language = "English",
volume = "212",
pages = "314--323",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "2",

}

Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia. / 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.

In: Experimental Neurology, Vol. 212, No. 2, 01.08.2008, p. 314-323.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Late expression of Na+/H+ exchanger 1 (NHE1) and neuroprotective effects of NHE inhibitor in the gerbil hippocampal CA1 region induced by transient ischemia

AU - Hwang, In Koo

AU - Yoo, Ki Yeon

AU - An, Sung Jin

AU - Li, Hua

AU - Lee, Choong Hyun

AU - Choi, Jung Hoon

AU - Lee, Jae Yong

AU - Lee, Bong Hee

AU - Kim, Young Myeong

AU - Kwon, Young-Guen

AU - Won, Moo Ho

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=47349123481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47349123481&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2008.04.007

DO - 10.1016/j.expneurol.2008.04.007

M3 - Article

VL - 212

SP - 314

EP - 323

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 2

ER -