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Published on: November 20, 2015
Is Late Prevention of Cerebral Palsy in Extremely Preterm Infants Plausible?
Benjamin A Lear1, Christopher A Lear1, Simerdeep K Dhillon1
1The Department of Physiology, University of Auckland, Auckland, New Zealand.
Insights
Cystic white matter injury (WMI) in preterm infants can evolve for weeks after birth, potentially leading to cerebral palsy. Early therapeutic intervention after hypoxic-ischemic (HI) injury may prevent delayed lesion development.
Area of Science:
- Neuroscience
- Neonatal research
- Developmental biology
Background:
- Preterm birth is linked to neurodevelopmental issues, notably cerebral palsy.
- Cystic white matter injury (WMI) is a primary neuropathology in cerebral palsy, affecting 1-3% of preterm infants.
- The exact pathogenesis and evolution of WMI remain poorly understood, despite falling incidence rates.
Purpose of the Study:
- To review preclinical evidence on the evolution of cystic WMI after hypoxic-ischemic (HI) injury.
- To investigate the potential for a therapeutic window to prevent delayed WMI and reduce cerebral palsy risk.
Main Methods:
- Review of preclinical studies examining WMI development post-HI.
- Analysis of evidence linking microglia activity to WMI evolution.
- Correlation of imaging findings with injury timelines.
Main Results:
- Severe, cystic WMI can evolve over many weeks following acute HI.
- Microglia activity is associated with the progression of WMI.
- Delayed lesion development observed clinically suggests a prolonged injury process.
Conclusions:
- The tertiary phase of HI injury may be a significant contributor to WMI.
- A therapeutic window of 1-2 weeks post-HI may exist to prevent delayed cystic lesions.
- Targeting this window could reduce the incidence of cerebral palsy in preterm infants.
Abstract:
Preterm birth continues to be associated with neurodevelopmental problems including cerebral palsy. Cystic white matter injury (WMI) is still the major neuropathology underlying cerebral palsy, affecting 1-3% of preterm infants. Although rates have gradually fallen over time, the pathogenesis and evolution of cystic WMI are still poorly understood. Hypoxia-ischemia (HI) remains an important contributor, yet there is no established treatment to prevent injury. Clinically, serial ultrasound and magnetic resonance imaging studies typically show delayed development of cystic lesions 2-4 weeks after birth. This raises the important and unresolved question as to whether this represents slow evolution of injury occurring around the time of birth or repeated injury over many weeks after birth. There is increasing evidence that tertiary injury after HI can contribute to impairment of white and grey matter maturation. In the present review, we discuss preclinical evidence that severe, cystic WMI can evolve for many weeks after acute HI and is associated with microglia activity. This suggests the intriguing hypothesis that the tertiary phase of injury is not as subtle as often thought and that there may be a window of therapeutic opportunity for 1 to 2 weeks after hypoxic-ischemic injury to prevent delayed cystic lesions, and so, further reduce the risk of cerebral palsy after preterm birth.
