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A Battery of Motor Tests in a Neonatal Mouse Model of Cerebral Palsy
Published on: November 3, 2016
Cell therapy for neonatal hypoxia-ischemia and cerebral palsy
Laura Bennet1, Sidhartha Tan, Lotte Van den Heuij
1Department of Physiology, University of Auckland, New Zealand.
Insights
Stem/progenitor cells show promise for treating perinatal hypoxic-ischemic brain injury, a cause of cerebral palsy. Further research in animal models is needed to clarify optimal use before human trials.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Neonatal Research
Background:
- Perinatal hypoxic-ischemic (HI) brain injury is a leading cause of cerebral palsy.
- Therapeutic hypothermia improves outcomes in term infants but isn't tested in preterm infants.
- Stem/progenitor cells show potential benefits for neurological impairment after HI injury.
Purpose of the Study:
- To review the potential of stem/progenitor cells in treating perinatal hypoxic-ischemic brain injury.
- To identify the gaps in knowledge regarding mechanisms, optimal cell type, dose, and administration.
- To assess the readiness of cell-based therapies for clinical trials in neonates.
Main Methods:
- Review of in vitro and in vivo preclinical studies on stem/progenitor cell interventions.
- Analysis of evidence for efficacy and safety of cell-based therapies.
- Evaluation of the current understanding of stem cell mechanisms in HI injury.
Main Results:
- Stem/progenitor cells demonstrate potential in preclinical models to reduce neurological deficits.
- Mechanisms of action, optimal cell types, doses, and administration methods remain unclear.
- Some studies report no significant benefit, highlighting variability in findings.
Conclusions:
- Cell-based interventions may improve functional outcomes for neonates with HI injury, particularly after secondary cell death.
- Rigorous testing in translational animal models is essential before considering randomized controlled trials.
- Further research is required to optimize stem/progenitor cell therapy for perinatal brain injury.
Abstract:
Perinatal hypoxic-ischemic brain injury remains a major cause of cerebral palsy. Although therapeutic hypothermia is now established to improve recovery from hypoxia-ischemia (HI) at term, many infants continue to survive with disability, and hypothermia has not yet been tested in preterm infants. There is increasing evidence from in vitro and in vivo preclinical studies that stem/progenitor cells may have multiple beneficial effects on outcome after hypoxic-ischemic injury. Stem/progenitor cells have shown great promise in animal studies in decreasing neurological impairment; however, the mechanisms of action of stem cells, and the optimal type, dose, and method of administration remain surprisingly unclear, and some studies have found no benefit. Although cell-based interventions after completion of the majority of secondary cell death appear to have potential to improve functional outcome for neonates after HI, further rigorous testing in translational animal models is required before randomized controlled trials should be considered.
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