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Neuroprotective effects of psalmotoxin‐1 in putamen after hypoxia‐ischemia in newborn piglet
Author(s) -
Yang Zengjin,
Martin Lee J,
Koehler Raymond C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1276-c
Subject(s) - asphyxia , hypoxia (environmental) , medicine , anesthesia , acidosis , ischemia , neuroprotection , endocrinology , cardiology , chemistry , oxygen , organic chemistry
Acidosis is thought to play an important role in cerebral ischemic injury. In an adult stroke model, inhibition of the Ca 2+ ‐permeable acid‐sensing ion channels (ASIC1a) by psalmotoxin‐1 (PcTX) reduced injury. We postulated that PcTX attenuates neuronal damage in selectively vulnerable striatum in a global model of neonatal hypoxic‐ischemic (HI) encephalopathy. H‐I consisted of 40 min of hypoxia (9.8% O2) followed by 7 min of asphyxia in 5‐7 day‐old piglets. PcTX (1 μg) or CSF vehicle (50 μl) was injected into each lateral ventricle 20 min before H‐I. No significant differences occurred at 37 min of hypoxia in P a O2 (21±3 Torr both groups; ±SD) or arterial pressure (MABP; CSF=94±16; PcTX=82±18 mmHg). During subsequent asphyxia, arterial O2 saturation decreased to 4±4% and 5±3%, arterial pH decreased to 6.82±0.07 and 6.85±0.09, and MABP decreased to 22±17 and 25±9 mmHg in the corresponding CSF and PcTX groups. The density of viable neurons in putamen 4 d later was increased from 20±6% (% of sham) in the CSF group to 54±28% in the PcTX group. We conclude that blocking ASIC1a activation with PcTX protected the highly vulnerable putamen neurons from ischemic death in immature brain. (Supported by NS20020)