Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiologicas, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Tecnicas, Buenos Aires, Argentina.
Departamento de Nutricion y Bioquimica, Facultad de Ciencias, Pontificia Universidad Javeriana Bogota, D.C, Colombia.
Curr Neuropharmacol. 2019;17(9):874-890. doi: 10.2174/1570159X17666181206101314.
Hypoxic-ischemic brain injury is a complex network of factors, which is mainly characterized by a decrease in levels of oxygen concentration and blood flow, which lead to an inefficient supply of nutrients to the brain. Hypoxic-ischemic brain injury can be found in perinatal asphyxia and ischemic-stroke, which represent one of the main causes of mortality and morbidity in children and adults worldwide. Therefore, knowledge of underlying mechanisms triggering these insults may help establish neuroprotective treatments. Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators exert several neuroprotective effects, including a decrease of reactive oxygen species, maintenance of cell viability, mitochondrial survival, among others. However, these strategies represent a traditional approach of targeting a single factor of pathology without satisfactory results. Hence, combined therapies, such as the administration of therapeutic hypothermia with a complementary neuroprotective agent, constitute a promising alternative. In this sense, the present review summarizes the underlying mechanisms of hypoxic-ischemic brain injury and compiles several neuroprotective strategies, including Selective Estrogen Receptor Modulators and Selective Tissue Estrogenic Activity Regulators, which represent putative agents for combined therapies with therapeutic hypothermia.
缺氧缺血性脑损伤是一个复杂的因素网络，主要特征是氧浓度和血流量降低，导致大脑营养供应效率低下。缺氧缺血性脑损伤可发生在围产期窒息和缺血性中风中，这是全球儿童和成人死亡和发病的主要原因之一。因此，了解引发这些损伤的潜在机制可能有助于建立神经保护治疗方法。选择性雌激素受体调节剂和选择性组织雌激素活性调节剂发挥多种神经保护作用，包括减少活性氧、维持细胞活力、线粒体存活等。然而，这些策略代表了针对单一病理因素的传统方法，结果并不令人满意。因此，联合治疗，如使用补充神经保护剂的治疗性低温，是一种有前途的替代方法。在这个意义上，本综述总结了缺氧缺血性脑损伤的潜在机制，并编译了几种神经保护策略，包括选择性雌激素受体调节剂和选择性组织雌激素活性调节剂，它们代表了与治疗性低温联合治疗的潜在药物。
