Progesterone improves motor coordination impairments caused by postnatal hypoxic-ischemic brain insult in neonatal male rats

被引:2
作者
Piao, Hongying [1 ]
Ishikawa, Hiroshi [1 ]
Kobayashi, Tatsuya [1 ,2 ,3 ]
Kitajo, Keiko [4 ]
Yamaguchi, Atsushi [4 ]
Koga, Kaori [1 ]
Shozu, Makio [1 ,5 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Obstet & Gynecol, Reprod Med, 1-8-1 Inohana,Chuo Ku, Chiba 2608670, Japan
[2] Fujita Hlth Univ, Sch Med Sci, Dept Regulatory Sci, Res Promot Unit, Toyoake, Aichi, Japan
[3] Fujita Hlth Univ, Haneda Clin, Tokyo, Japan
[4] Chiba Univ, Grad Sch Med, Dept Funct Anat, Chiba, Japan
[5] Chiba Univ, Med Mycol Res Ctr, Evolut & Reprod Biol, Chiba, Japan
基金
日本学术振兴会;
关键词
Brain hypoxia-ischemia; Cerebral palsy; Premature infant; Progesterone; Rotarod performance test; PRETERM BIRTH; INJURY; SEX; MULTICENTER; CELLS; MODEL;
D O I
10.1016/j.pedneo.2024.03.012
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background: Hypoxic-ischemic (HI) insult in infants induces brain injury and results in motor coordination impairments associated with cerebral palsy; however, preventive measures for HI brain injury in preterm infants remain unclear. We investigated the impact of progesterone (P4) in a rat HI insult model that mimics HI brain injury in preterm infants. Methods: Neonatal male rats with their right common carotid artery coagulated were exposed to a 1-h hypoxia (6% oxygen) on postnatal day (PND) 3. P4 (0.2 mg) was subcutaneously administered daily from PND4-12. Motor coordination function and muscular strength were evaluated on PND50 using rotarod and grip strength tests, respectively. Brain histology was evaluated via immunohistochemistry using anti-NeuN, anti-Olig2, and anti-IbaI antibodies on PND15 and PND50. Results: In male rats, P4 significantly improved the latency-to-fall off on the rotarod test in the insult rats to the levels of the sham-operation rats. Neither the insult nor P4 administration impacted the grip strength results. No significant differences were observed in the number of neurons, oligodendrocyte progenitor cells (OPCs), and microglia in the motor and somatosensory area of the cortex between the insult and insult followed by P4administered rats on PND50. The number of OPCs in the corpus callosum was significantly increased in the ipsilateral side compared with the contralateral side of the insult in the P4-administered rats, indicating that P4 facilitates recruitment of OPCs to the corpus callosum. HI insult accelerated neuronal differentiation in rats on PND15, which was abrogated in the P4-administerd group, suggesting that P4 suppresses transient neuronal differentiation caused by the insult. Conclusion: P4 administration restored motor coordination impairments caused by postnatal HI insult in male rats. The insult timing corresponds to that of human preterm infants, indicating P4's potential for protecting HI brain injury in preterm male infants.
引用
收藏
页码:216 / 222
页数:7
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