Intranasal delivery of cell-penetrating anti-NF-κB peptides (Tat-NBD) alleviates infection-sensitized hypoxic-ischemic brain injury.
Intranasal delivery of cell-penetrating anti-NF-κB peptides (Tat-NBD) alleviates infection-sensitized hypoxic-ischemic brain injury.
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细胞渗透抗NF-κB肽（TAT-NBD）的鼻内递送减轻感染敏感的低氧缺血性脑损伤。
DOI：
10.1016/j.expneurol.2013.01.015
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Kuan, Chia-Yi
中科院分区：
文献类型：
--
作者：
Yang, Dianer;Sun, Yu-Yo;Lin, Xiaoyi;Baumann, Jessica M.;Dunn, R. Scott;Lindquist, Diana M.;Kuan, Chia-Yi
Perinatal infection aggravates neonatal hypoxic-ischemic (HI) brain injury and may interfere with therapeutic hypothermia. While the NF-κB signaling pathway has been implicated in microglia activation in infection-sensitized HI, the current therapeutic strategies rely on systemic intervention, which could impair neonatal immunity and increase the risk of severe infection. To devise a brain-targeted anti-NF-κB strategy, we examined the effects of intranasal delivery of tat-NBD peptides in two animal models of neonatal infection-sensitized HI. Kinetics experiments showed that tat-NBD peptides entered the olfactory bulbs rapidly (10-30 min) and peaked in the cerebral cortex around 60 min after intranasal application in P7 rats. Further, intranasal delivery of 1.4 mg/kg tat-NBD, which is only 7% of the intravenous dose in past studies, markedly attenuated NF-κB signaling, microglia activation, and brain damage triggered by HI with 4 or 72 h pre-exposure to the bacterial endotoxin lipopolysaccharide (LPS). In contrast, intranasal delivery of mutant tat-NBD peptides or systemic application of minocycline failed to block LPS-sensitized HI injury. Yet, intranasal delivery of up to 5.6 mg/kg tat-NBD peptides immediately after pure-HI insult showed litter protection, likely due to its rapid clearance from the brain and inability to inhibit parenchymal plasminogen activators. Together, these results suggest a novel therapy of infection-sensitized HI brain injury in newborns.
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影响因子：
3
作者：
Sun, Yu-Yo;Yang, Dianer;Kuan, Chia-Yi
通讯作者：
Kuan, Chia-Yi
影响因子：
8.3
作者：
Nijboer, Cora H.;Heijnen, Cobi J.;Kavelaars, Annemieke
通讯作者：
Kavelaars, Annemieke
影响因子：
4.5
作者：
Alcalá-Barraza SR;Lee MS;Hanson LR;McDonald AA;Frey WH 2nd;McLoon LK
通讯作者：
McLoon LK
影响因子：
6.2
作者：
Choi, Judy;Ifuku, Masataka;Noda, Mami;Guilarte, Tomas R.
通讯作者：
Guilarte, Tomas R.
DOI：
10.1523/jneurosci.0698-11.2011
发表时间：
2011-06-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Akpan N;Serrano-Saiz E;Zacharia BE;Otten ML;Ducruet AF;Snipas SJ;Liu W;Velloza J;Cohen G;Sosunov SA;Frey WH 2nd;Salvesen GS;Connolly ES Jr;Troy CM
通讯作者：
Troy CM