THE NUCLEAR FACTOR ERYTHROID 2-LIKE 2 ACTIVATOR, TERT-BUTYLHYDROQUINONE, IMPROVES COGNITIVE PERFORMANCE IN MICE AFTER MILD TRAUMATIC BRAIN INJURY
THE NUCLEAR FACTOR ERYTHROID 2-LIKE 2 ACTIVATOR, TERT-BUTYLHYDROQUINONE, IMPROVES COGNITIVE PERFORMANCE IN MICE AFTER MILD TRAUMATIC BRAIN INJURY
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DOI：
10.1016/j.neuroscience.2012.07.070
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发表时间：
2012-10-25
期刊：
影响因子：
3.3
通讯作者：
Citron, B. A.
中科院分区：
文献类型：
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作者：
Saykally, J. N.;Rachmany, L.;Citron, B. A.
创伤性脑损伤仅在美国每年就影响至少170万人。大多数伤害被归类为轻度，但这些仍然产生困扰患者和医疗领域的持久症状。目前的治疗旨在减轻患者的症状，但没有有效的方法来对抗问题的根源，神经元损失。我们测试了一个轻度的，封闭的头部创伤性脑损伤模型的抗氧化剂转录因子Nrf 2的化学激活剂，叔丁基对苯二酚（tBHQ）的调制的影响。我们发现损伤后的视觉记忆通过7天的疗程得到改善，并且海马中活化的半胱天冬酶-3的水平降低。在损伤后30 min单次注射也可逆转损伤诱导的记忆丧失。由于保护性应激反应分子HSP 70可以被Nrf 2上调，我们检测了海马中的蛋白水平，发现HSP 70因损伤而升高，然后通过治疗进一步增加。为了测试HSP 70的可能作用，暴露于轻度损伤并用Nrf 2激活剂处理的培养物中的模型神经元显示出被HSP 70抑制剂VER 155008阻断的改善的存活。在轻度创伤性脑损伤后，可能会出现部分保护性反应，患者可以从直接增强调节通路（如Nrf 2）中获益。由Elsevier Ltd.代表IBRO出版。
Traumatic Brain injury affects at least 1.7 million people in the United States alone each year. The majority of injuries are categorized as mild but these still produce lasting symptoms that plague the patient and the medical field. Currently treatments are aimed at reducing a patient's symptoms, but there is no effective method to combat the source of the problem, neuronal loss. We tested a mild, closed head traumatic brain injury model for the effects of modulation of the antioxidant transcription factor Nrf2 by the chemical activator, tert-butylhydroquinone (tBHQ). We found that post-injury visual memory was improved by a 7 day course of treatment and that the level of activated caspase-3 in the hippocampus was reduced. The injury-induced memory loss was also reversed by a single injection at 30 min after injury. Since the protective stress response molecule, HSP70, can be upregulated by Nrf2, we examined protein levels in the hippocampus, and found that HSP70 was elevated by the injury and then further increased by the treatment. To test the possible role of HSP70, model neurons in culture exposed to a mild injury and treated with the Nrf2 activator displayed improved survival that was blocked by the HSP70 inhibitor, VER155008. Following mild traumatic brain injury, there may be a partial protective response and patients could benefit from directed enhancement of regulatory pathways such as Nrf2 for neuroprotection. Published by Elsevier Ltd. on behalf of IBRO.