Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury.
Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury.
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DOI：
10.1177/1849543520970819
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发表时间：
2020-01
期刊：
影响因子：
--
通讯作者：
Nance E
中科院分区：
文献类型：
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作者：
Liao R;Wood TR;Nance E
兴奋性中毒是中风、创伤性脑损伤 (TBI) 和围产期窒息等全脑缺血期间发生的主要病理过程。兴奋性毒性是由突触内过多的兴奋性神经递质引发的，导致钠和钙过量流入、产生活性氧、线粒体损伤并最终导致细胞死亡的有害级联反应。有多个潜在的干预点可以对抗兴奋性毒性和下游氧化应激，但目前尚无临床批准用于此特定目的的治疗方法。为了使治疗剂能够有效对抗兴奋性毒性，治疗剂必须在正确的时间以适当的浓度积聚在疾病部位。纳米技术可以为治疗递送带来好处，包括克服血脑屏障等生理障碍、保护货物免于降解以及提供药物的受控释放。本综述评估了使用纳米疗法对抗中风、脑外伤和缺氧缺血中的兴奋性毒性，重点是减轻氧化应激，并考虑临床转化的路径。
Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood–brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia–ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.