Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum
Na+,Ca2+-permeable acid-sensing ion channel 1a (ASIC1a) is involved in the pathophysiologic process of adult focal brain ischemia. However, little is known about its role in the pathogenesis of global cerebral ischemia or newborn hypoxia–ischemia (H–I). Here, using a newborn piglet model of asphyxia...
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| Format: | Article |
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Elsevier
2011-08-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996111001355 |
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| author | Zeng-Jin Yang Xinli Ni Erin L. Carter Kathleen Kibler Lee J. Martin Raymond C. Koehler |
| author_facet | Zeng-Jin Yang Xinli Ni Erin L. Carter Kathleen Kibler Lee J. Martin Raymond C. Koehler |
| author_sort | Zeng-Jin Yang |
| collection | DOAJ |
| description | Na+,Ca2+-permeable acid-sensing ion channel 1a (ASIC1a) is involved in the pathophysiologic process of adult focal brain ischemia. However, little is known about its role in the pathogenesis of global cerebral ischemia or newborn hypoxia–ischemia (H–I). Here, using a newborn piglet model of asphyxia-induced cardiac arrest, we investigated the effect of ASIC1a-specific blocker psalmotoxin-1 on neuronal injury. During asphyxia and the first 30 min of recovery, brain tissue pH fell below 7.0, the approximate activation pH of ASIC1a. Psalmotoxin-1 injection at 20 min before hypoxia, but not at 20 min of recovery, partially protected the striatonigral and striatopallidal neurons in putamen. Psalmotoxin-1 pretreatment largely attenuated the increased protein kinase A-dependent phosphorylation of DARPP-32 and N-methyl-d-aspartate (NMDA) receptor NR1 subunit and decreased nitrative and oxidative damage to proteins at 3 h of recovery. Pretreatment with NMDA receptor antagonist MK-801 also provided partial neuroprotection in putamen, and combined pretreatment with psalmotoxin-1 and MK-801 yielded additive neuroprotection. These results indicate that ASIC1a activation contributes to neuronal death in newborn putamen after H–I through mechanisms that may involve protein kinase A-dependent phosphorylation of NMDA receptor and nitrative and oxidative stress. |
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| id | doaj.art-5603426667e84f20ae20675ab615227f |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T21:34:14Z |
| publishDate | 2011-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-5603426667e84f20ae20675ab615227f2022-12-21T21:31:47ZengElsevierNeurobiology of Disease1095-953X2011-08-01432446454Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatumZeng-Jin Yang0Xinli Ni1Erin L. Carter2Kathleen Kibler3Lee J. Martin4Raymond C. Koehler5Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA; Corresponding author at: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, 720 Rutland Ave, Traylor 809, Baltimore, MD 21205, USA. Fax: +1 410 502 5177.Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USADepartment of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USADepartment of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USADivision of Neuropathology, Department of Pathology, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USADepartment of Anesthesiology/Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USANa+,Ca2+-permeable acid-sensing ion channel 1a (ASIC1a) is involved in the pathophysiologic process of adult focal brain ischemia. However, little is known about its role in the pathogenesis of global cerebral ischemia or newborn hypoxia–ischemia (H–I). Here, using a newborn piglet model of asphyxia-induced cardiac arrest, we investigated the effect of ASIC1a-specific blocker psalmotoxin-1 on neuronal injury. During asphyxia and the first 30 min of recovery, brain tissue pH fell below 7.0, the approximate activation pH of ASIC1a. Psalmotoxin-1 injection at 20 min before hypoxia, but not at 20 min of recovery, partially protected the striatonigral and striatopallidal neurons in putamen. Psalmotoxin-1 pretreatment largely attenuated the increased protein kinase A-dependent phosphorylation of DARPP-32 and N-methyl-d-aspartate (NMDA) receptor NR1 subunit and decreased nitrative and oxidative damage to proteins at 3 h of recovery. Pretreatment with NMDA receptor antagonist MK-801 also provided partial neuroprotection in putamen, and combined pretreatment with psalmotoxin-1 and MK-801 yielded additive neuroprotection. These results indicate that ASIC1a activation contributes to neuronal death in newborn putamen after H–I through mechanisms that may involve protein kinase A-dependent phosphorylation of NMDA receptor and nitrative and oxidative stress.http://www.sciencedirect.com/science/article/pii/S0969996111001355Acid-sensing ion channelHypoxia–ischemiaNewbornNeuroprotectionStriatum |
| spellingShingle | Zeng-Jin Yang Xinli Ni Erin L. Carter Kathleen Kibler Lee J. Martin Raymond C. Koehler Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum Neurobiology of Disease Acid-sensing ion channel Hypoxia–ischemia Newborn Neuroprotection Striatum |
| title | Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum |
| title_full | Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum |
| title_fullStr | Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum |
| title_full_unstemmed | Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum |
| title_short | Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia–ischemia in newborn piglet striatum |
| title_sort | neuroprotective effect of acid sensing ion channel inhibitor psalmotoxin 1 after hypoxia ischemia in newborn piglet striatum |
| topic | Acid-sensing ion channel Hypoxia–ischemia Newborn Neuroprotection Striatum |
| url | http://www.sciencedirect.com/science/article/pii/S0969996111001355 |
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