期刊
STROKE
卷 41, 期 9, 页码 2050-2055出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.110.589051
关键词
apoptosis; Bax; neonatal ischemia; neuroprotection
资金
- Swedish Medical Research Council [VR K2009-54X-21119-01-4, VR 2006-3396]
- Wilhelm and Martina Lundgren [vet2-37/2009]
- Linnea och Josef Carlssons stiftelse
- National Natural Science Foundation of China [30973240]
- Swedish government [ALFGBG2863]
- Medical Research Council in United Kingdom [P19381]
- MRC [G0802853] Funding Source: UKRI
- Action Medical Research [1764] Funding Source: researchfish
- Medical Research Council [G0802853] Funding Source: researchfish
- Austrian Science Fund (FWF) [P19381] Funding Source: Austrian Science Fund (FWF)
Background and Purpose-Mitochondria play a critical role in mediating cell death in both the adult and immature brain. The cyclophilin D mitochondrial membrane permeability transition pore is critical in adult ischemia, whereas in neonatal hypoxic-ischemic (HI) brain injury, mitochondrial permeabilization appears to be primarily Bax-dependent. The aim of this study was to evaluate the neuroprotective effect of a cell-penetrating Bax-inhibiting peptide (BIP) on neonatal mouse HI brain injury. Methods-BIP (5 mu L, 5 mg/mL) or a BIP-negative control (5 mu L, 5 mg/mL) was injected intracerebroventricularly immediately before HI in postnatal day 9 mice. Mice were euthanized at different time points after HI for evaluation of brain injury, Bax activation, release of proapoptotic proteins, and caspase activation. The trace fear conditioning and cylinder tests were performed for evaluation of the functional recovery after BIP treatment. Results-At 5 days after HI, there was a 41.2% reduction of brain injury in BIP-treated mice compared with BIP-negative control treated animals. Myelin basic protein and neurofilament quantification revealed that BIP reduced white matter injury. BIP treatment conferred improvement in both sensorimotor and memory functions at 7 weeks after HI. BIP protection was associated with a reduction of Bax activation, mitochondrial permeabilization, and downstream caspase activation. Conclusions-Bax inhibition provides neuroprotection and functional improvement in a neonatal mouse model of HI. (Stroke. 2010;41:2050-2055.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据