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Published on: October 25, 2016
17beta-estradiol protects the neonatal brain from hypoxia-ischemia
Joseph Nuñez1, Zhengang Yang, Yuhui Jiang
1Department of Psychology, Michigan State University, 138 Giltner Hall, East Lansing, MI 48824, USA. nunezj@msu.edu
Insights
Repeated doses of 17beta-estradiol significantly protected the developing rat brain from hypoxia-ischemia injury. This suggests potential therapeutic benefits of 17beta-estradiol for infants at risk of brain damage.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Medicine
Background:
- Neonatal hypoxic-ischemic encephalopathy (HIE) is a common birth complication.
- Infants often experience cognitive and behavioral deficits following HIE.
- The immature brain shows some resilience to HIE, suggesting protective factors.
Purpose of the Study:
- To investigate the neuroprotective potential of 17beta-estradiol in neonatal hypoxia-ischemia.
- To determine if elevated 17beta-estradiol levels can mitigate HIE-induced brain injury in developing rats.
Main Methods:
- Immature male and female rats were administered 17beta-estradiol.
- Two dosing paradigms were used: repeated doses and a single dose 24 hours prior to HIE.
- Brain damage was assessed following induced hypoxia-ischemia.
Main Results:
- Repeated 17beta-estradiol administration provided ~70% protection to the hippocampus, basal ganglia, and amygdala.
- A single dose of 17beta-estradiol offered minimal protection, except in the female hippocampus.
- Protection was comparable between males and females, with males showing greater protection in the amygdala.
Conclusions:
- 17beta-estradiol is a potent neuroprotective agent against HIE in the developing brain.
- Repeated administration is more effective than a single dose.
- Pretreatment with 17beta-estradiol may be a viable strategy for infants at risk of HIE.
Abstract:
Hypoxia-ischemia is relatively common in human infants. Hypoxia-ischemia can occur as a result of complications associated with prematurity or birth, frequently leading to altered brain development and cognitive and behavioral deficits that persist throughout life. Despite the relative frequency of neonatal hypoxic-ischemic encephalopathy, the immature brain sustains relatively less damage than an adult who experiences a similar crisis of oxygen and nutrient deprivation. Therefore, factors may be present that protect the developing brain. During late gestation, the infant brain encounters high levels of the steroid hormone 17beta-estradiol. This observation, combined with evidence supporting 17beta-estradiol as a neuroprotective agent, led us to hypothesize that increasing the basal level of 17beta-estradiol would reduce the amount of hypoxia-ischemia induced injury to the neonatal brain. To test that hypothesis we administered 17beta-estradiol using either a repeated dosing paradigm or a single dose paradigm to immature male and female rats. Here we show that the repeated dosing paradigm (three doses of 17beta-estradiol) provided approximately 70% protection of the hippocampus, basal ganglia, and amygdala. By contrast, a single administration of 17beta-estradiol 24 h prior to hypoxia-ischemia conferred little protection. The only exception was the pyramidal layer of the female hippocampus, which was modestly protected (16% reduction in damage). The protection afforded by the multiple administrations of 17beta-estradiol was similar for females and males, with the only exception being the male amygdala, which displayed less damage than the female amgydala. We conclude that 17beta-estradiol acts as a potent neuroprotective agent against hypoxia-ischemia induced damage to the developing brain, and that pretreating infants at risk for hypoxic-ischemic injury may be advisable.
