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A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Progesterone improves motor coordination impairments caused by postnatal hypoxic-ischemic brain insult in neonatal
Hongying Piao1, Hiroshi Ishikawa1, Tatsuya Kobayashi2
1Department of Obstetrics and Gynecology, Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Insights
Progesterone (P4) treatment improved motor coordination in male rats following hypoxic-ischemic (HI) brain injury. This suggests P4 may protect preterm infants from HI-induced brain damage and related impairments.
Area of Science:
- Neuroscience
- Neonatal Research
- Developmental Biology
Background:
- Hypoxic-ischemic (HI) insult in infants causes brain injury and motor impairments, potentially leading to cerebral palsy.
- Effective preventive measures for HI brain injury in preterm infants are currently lacking.
- This study investigates the neuroprotective potential of progesterone (P4) in a rat model of HI brain injury.
Purpose of the Study:
- To evaluate the efficacy of progesterone (P4) in mitigating motor coordination deficits following a neonatal hypoxic-ischemic (HI) insult in a rat model.
- To assess the impact of P4 on neuronal survival, oligodendrocyte progenitor cell (OPC) recruitment, and microglial response in the developing brain after HI insult.
- To determine if P4 influences the timing of neuronal differentiation in response to HI insult.
Main Methods:
- Neonatal male rats underwent a hypoxic-ischemic (HI) insult on postnatal day 3.
- Progesterone (P4) was administered daily from postnatal day 4 to 12.
- Motor coordination (rotarod test) and grip strength were assessed on postnatal day 50.
- Brain histology was analyzed using immunohistochemistry for neurons (NeuN), OPCs (Olig2), and microglia (Iba1) at postnatal days 15 and 50.
Main Results:
- P4 administration significantly restored motor coordination deficits in HI-insulted rats to levels comparable to sham-operated controls.
- While P4 did not affect grip strength, it increased OPC numbers in the corpus callosum, suggesting enhanced glial cell recruitment.
- HI insult accelerated early neuronal differentiation, an effect that was suppressed by P4 treatment, indicating a modulation of developmental processes.
Conclusions:
- Progesterone (P4) effectively restored motor coordination impairments resulting from neonatal hypoxic-ischemic (HI) insult in male rats.
- The timing of the HI insult in this model aligns with that of human preterm infants.
- These findings highlight the potential of P4 as a therapeutic agent for protecting preterm male infants against HI brain injury.
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 P4-administered 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.
