Marked age-dependent neuroprotection by brain-derived neurotrophic factor against neonatal hypoxic-ischemic brain injury
Marked age-dependent neuroprotection by brain-derived neurotrophic factor against neonatal hypoxic-ischemic brain injury
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DOI：
10.1002/ana.410410416
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发表时间：
1997-04-01
影响因子：
11.2
通讯作者：
Holtzman, DM
中科院分区：
文献类型：
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作者：
Cheng, Y;Gidday, JM;Holtzman, DM
围产期窒息后新生儿缺氧缺血性脑损伤是临床上常见的问题，目前尚无有效的治疗方法。神经营养因子，如脑源性神经营养因子（BDNF），可以保护响应神经元免受细胞死亡，在一些损伤范例。虽然BDNF在缺氧缺血性脑损伤中的作用尚不清楚，但有证据表明BDNF在发育中的大脑中可能具有不同的作用，而不是成人大脑。我们发现，单次脑室内（ICV）注射脑源性神经营养因子会导致出生后第7天（PD）大鼠大脑多个脑区trk受体快速而强烈的磷酸化。BDNF在PD7时也明显保护缺氧缺血性脑损伤。当在损伤之前给予时，其防止90%的由于缺氧缺血引起的组织损失，并且当在损伤之后给予时，其防止50%的组织损失。相比之下，在PD21和成年大鼠中ICV注射BDNF导致很少的trk磷酸化，并且在PD21时对单侧缺氧缺血性损伤的保护作用较小。由于BDNF在发育中的大脑中具有强大的神经保护作用，因此它可能是围产期窒息和其他形式急性损伤的潜在治疗方法。
Hypoxic-ischemic brain injury in survivors of perinatal asphyxia is a frequently encountered clinical problem for which there is currently no effective therapy. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), can protect responsive neurons against cell death in some injury paradigms. While the role of BDNF in hypoxic-ischemic brain injury is not dear, evidence suggests that BDNF may have different effects in the developing, as opposed to the adult, brain. We found that a single intracerebroventricular (ICV) injection of BDNF resulted in rapid and robust phosphorylation of trk receptors in multiple brain regions in the postnatal day (PD) 7 rat brain. BDNF also markedly protected against hypoxic-ischemic brain injury at PD7. It protected against 90% of tissue loss due to hypoxic-ischemia when given just prior to the insult and against 50% of tissue loss when give after the insult. In contrast, ICV injection of BDNF in PD21 and adult rats resulted in little trk phosphorylation and less dramatic protection against unilateral hypoxic-ischemic injury at PD21. Because of its potent neuroprotective actions in the developing brain, BDNF may be a potential treatment for asphyxia and other forms of acute injury in the perinatal period.