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KMID : 1101620160270030149
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Perinatology
2016 Volume.27 No. 3 p.149 ~ p.157
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Neuroprotective Effects of SYM 2081, Targeting Kainate Receptors in the Neonatal Hypoxic-Ischemic Brain Injury
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Lee Jong-Hoon
Lee Eun-Joo
Jang Yoon-Young
Jeong Ji-Eun
Chung Hai-Lee
Kim Woo-Taek
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Abstract
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Purpose: Glutamate induced excitotoxicity has been implicated as a major factor of central neuronal death in neonatal hypoxic-ischemic (HI) injury. Kainate receptors (KARs) are one of glutamatergic receptors involving glutamate toxicity. However, the expression patterns of KARs in the neonatal HI brain injury have not been clearly established. Therefore, this study was designed to investigate the expression pattern of KARs and to determine the potential of SYM 2081 ((2S, 4R)-4-methylglutamic acid) as a neuronal rescue agent after HI brain injury.
Methods: In an in vivo model, left carotid artery ligation (LCA) was done in Sprague-Dawley (SD) rat pups. The animals were divided into five groups; normoxia (N), hypoxia (8% O2, 92% N2) (H), hypoxia with sham-operation (HS), hypoxia with operation (HO), and HO treated with SYM 2081 before a hypoxic insult (HM). In an in vitro model, the cultured embryonic cortical neuronal cells were divided into three groups: normoxia (95% air, 5% CO2) (Nc), hypoxia (94% N2, 5% CO2) (Hc), and Hc treated with SYM2081 (HMc) before a hypoxic insult. The expressions of GluK1-5 were assessed by real-time polymerase chain reaction.
Results: The area of left hemisphere was decreased as compared to contralateral hemisphere in HO group, restored by SYM 2081 treatment. Cell loss observed in the Hc group was decreased in the HMC group. The expressions of all KARs except for GluK2 were decreased in the HO and HC groups, whereas they were increased in HM and HMc groups.
Conclusion: This study showed that SYM 2081 had neuroprotective effects on HI brain injury in neonatal rats through modulating KAR expression.
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KEYWORD
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2S, 4R)-4-methylglutamic acid, Kainate, Brain-hypoxia-ischemia, Neuroprotection
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