Sex specific correlation between GABAergic disruption in the dorsal hippocampus and flurothyl seizure susceptibility after neonatal hypoxic-ischemic brain injury.
Sex specific correlation between GABAergic disruption in the dorsal hippocampus and flurothyl seizure susceptibility after neonatal hypoxic-ischemic brain injury.
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新生儿低氧 - 缺血性脑损伤后，背部海马中的GABA能破坏与氟洛氨基癫痫的敏感性之间的性别特异性相关性。
DOI：
10.1016/j.nbd.2020.105222
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发表时间：
2021-01
影响因子：
6.1
通讯作者：
Chavez-Valdez R
中科院分区：
文献类型：
--
作者：
Lechner CR;McNally MA;St Pierre M;Felling RJ;Northington FJ;Stafstrom CE;Chavez-Valdez R
由于新生儿缺氧缺血（HI）会破坏小鼠海马（Hp）GABA能网络，并且该模型中的Hp损伤仅与雄性小鼠的氟乙酸癫痫发作易感性相关，因此我们假设GABA能破坏与氟乙酸癫痫发作易感性以性别特异性方式相关。在P10将C57BL6小鼠暴露于HI（Vannucci模型）与假手术，随机分配至正常体温（NT）或治疗性低温（TH），随后在P18进行氟乙酸癫痫发作测试。只有在雄性小鼠中，Hp萎缩与癫痫易感性相关。HP parvalbumin阳性interneurons（PV+INs）的数量减少HI后，在两种性别，但TH衰减这种赤字只在女性。仅在男性中，癫痫发作易感性与PV+ IN的数量直接相关，但与生长抑素或钙视蛋白表达的IN无关。HI后Hp GABAB受体亚单位水平降低，但与以后的癫痫发作易感性无关。而HpGABAA受体α1亚单位（GABAARα1）在HI后则明显升高。根据GABAARα1的表达调整PV+ IN的数量，增强了与雄性小鼠癫痫易感性的相关性。因此，我们确定了一种新的Hp性别特异性GABA介导的HI后补偿机制，该机制与氟乙烯癫痫发作易感性相关，从而进一步研究以更好地了解潜在的临床转化。
Since neonatal hypoxia-ischemia (HI) disrupts the hippocampal (Hp) GABAergic network in the mouse and Hp injury in this model correlates with flurothyl seizure susceptibility only in male mice, we hypothesized that GABAergic disruption correlates with flurothyl seizure susceptibility in a sex-specific manner. C57BL6 mice were exposed to HI (Vannucci model) versus sham procedures at P10, randomized to normothermia (NT) or therapeutic hypothermia (TH), and subsequently underwent flurothyl seizure testing at P18. Only in male mice, Hp atrophy correlated with seizure susceptibility. The number of Hp parvalbumin positive interneurons (PV+INs) decreased after HI in both sexes, but TH attenuated this deficit only in females. In males only, seizure susceptibility directly correlated with the number of PV+INs, but not somatostatin or calretinin expressing INs. Hp GABAB receptor subunit levels were decreased after HI, but unrelated to later seizure susceptibility. In contrast, Hp GABAA receptor α1 subunit (GABAARα1) levels were increased after HI. Adjusting the number of PV+ INs for their GABAARα1 expression strengthened the correlation with seizure susceptibility in male mice. Thus, we identified a novel Hp sex-specific GABA-mediated mechanism of compensation after HI that correlates with flurothyl seizure susceptibility warranting further study to better understand potential clinical translation.
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影响因子：
2.9
作者：
Diaz J;Abiola S;Kim N;Avaritt O;Flock D;Yu J;Northington FJ;Chavez-Valdez R
通讯作者：
Chavez-Valdez R
影响因子：
5.1
作者：
Glass, Hannah C.;Glidden, David;Jeremy, Rita J.;Barkovich, A. James;Ferriero, Donna M.;Miller, Steven P.
通讯作者：
Miller, Steven P.
影响因子：
2.3
作者：
BEAL, MF;KOWALL, NW;MARTIN, JB
通讯作者：
MARTIN, JB
影响因子：
9.9
作者：
Glass, Hannah C.;Wusthoff, Courtney J.;Chang, Taeun
通讯作者：
Chang, Taeun
DOI：
10.1111/j.1749-6632.2003.tb07517.x
发表时间：
2003-01-01
期刊：
NEUROPROTECTIVE AGENTS
影响因子：
--
作者：
Bittigau, P;Sifringer, M;Ikonomidou, C
通讯作者：
Ikonomidou, C