Cerebral palsy

Michael V. Johnston, Alexander H. Hoon

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


Cerebral palsy (CP) is a group of disorders of movement and posture resulting from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of cases of CP in term infants originate in the prenatal period; in premature infants, both prenatal or postnatal causes contribute. The most prevalent pathological lesion seen in CP is periventricular white matter injury (PWMI) resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32 wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a spectrum of cognitive and behavioral disorders. Oxidative stress and excitotoxicity resulting from excessive stimulation of ionotropic glutamate receptors on preOLs are the most prominent molecular mechanisms for PWMI. Asphyxia around the time of birth in term infants accounts for less than 15% of CP in developed countries but the incidence is higher in underdeveloped areas. Asphyxia causes a different pattern of brain injury and CP than is seen after preterm injuries. This type of CP is associated with the clinical syndrome of hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal ganglia, and brainstem are selectively vulnerable to injury. Experimental models indicate that neurons in the neonatal brain are more likely to die by delayed apoptosis extending over days to weeks than those in the adult brain. Neurons die by glutamate-mediated excitotoxicity involving downstream caspase-dependent and caspase-independent cell death pathways. Recent reports indicate that males and females preferentially utilize different pathways. Clinical trials indicate that mild hypothermia reduces death or disability in term infants following asphyxia and basic research suggests that this approach might be combined with pharmacological strategies in the future.

Original languageEnglish (US)
Pages (from-to)435-450
Number of pages16
JournalNeuromolecular medicine
Issue number4
StatePublished - Dec 1 2006


  • Apoptosis
  • Apoptosis-inducing factor
  • Cerebral palsy
  • Gender
  • Hypoxic-ischemic encephalopathy
  • Periventricular leukomalacia
  • White matter

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience


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