Cerebral Palsy: Underlying Causes and Animal Models


Cerebral palsy (CP) was first discovered in 1853 by Dr. William Little. It is a non‐progressive motor disorder that occurs in approximately 2–4 of every 1000 live births. CP can be acquired, where insults occur during or after birth, or congenital, meaning insults occurred in utero. The major neurological hallmarks of CP are white matter injury around the ventricles and cortical dysgenesis, caused by insults in the developing brain before, during or after birth. These insults include haemorrhage or stroke, hypoxia, ischaemia, and infection (maternally or in the neonate) or inflammation, which lead to cellular responses in astrocytes, microglia, neurons and oligodendrocytes and subsequent brain damage. Rare genetic mutations can also cause CP and lead to changes in cortical organisation. Researchers are using animal models to elucidate the underlying cellular changes that lead to CP.

Key Concepts

  • Cerebral palsy most commonly occurs between 24 and 32 weeks of gestation in the developing brain.
  • Periventricular leukomalacia and cortical dysgenesis are the neurological hallmarks of cerebral palsy.
  • Different insults lead to acquired or congenital cerebral palsy and also vary the degree of brain injury.
  • The combination of hypoxia, ischaemia and inflammation is thought to lead to the majority of congenital CP.
  • The inflammatory response is initiated through the activation of microglia leading to astrocyte loss and delayed activation, neuron death and decreased white matter density.
  • Glutamate excitotoxicity occurs in response to injury and leads to neuron death and periventricular leukomalacia.
  • Animal models are integral in clarifying the cellular responses underlying the brain damage seen in cerebral palsy.

Keywords: cerebral palsy; animal models; periventricular leukomalacia; cortical dysgenesis; intrauterine infection; hypoxic‐ischaemic encephalopathy; inflammation

Figure 1. Acquired cerebral palsy. Acquired CP is the term given to cerebral palsy cases that are caused by a known insult or injury peri‐ or post‐partum, such as birth asphyxia or stroke. It accounts for 5–20% of all known CP cases in the United States. The initial injury leads to cellular changes in the infant brain that can trigger a cascade of cellular and molecular events, eventually leading to white matter damage around the ventricles (periventricular leukomalacia), neuronal damage or death and the motor deficits that are the classic symptoms of CP. As these injuries usually occur when the infant is near‐term, acquired CP often results in the ataxic form of cerebral palsy.
Figure 2. Congenital cerebral palsy. Congenital CP is the term given to cerebral palsy cases that develop from unknown causes. It usually occurs in utero and often is not diagnosed until the infant begins missing developmental milestones or has difficulty performing motor tasks, such as grasping, rolling over, crawling or walking. While the exact cause of congenital CP is not known, hypoxia (loss of oxygen), ischaemia (loss of blood flow) and infection/inflammation have been implicated because of the type of brain injury seen, as well as cytokine levels found in serum of human CP patients. Owing to the injury occurring in utero while the brain is still developing, congenital CP often results in the spastic form of cerebral palsy.


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Further Reading

Deng W, Pleasure J and Pleasure D (2008b) Progress in periventricular leukomalacia. Archives of Neurology 65: 1291–1295.

Hermansen MC and Hermansen MG (2006) Perinatal Infections and Cerebral Palsy. Clinics in Perinatology 33 (2): 315–333.

Jensen FE (2005b) Role of Glutamate Receptors in Periventricular Leukomalacia. Journal of Child Neurology 20: 950–959.

Moreno‐De‐Luca A, Ledbetter DH and Martin CL (2012b) Genetic [corrected] insights into the causes and classification of [corrected] cerebral palsies. The Lancet Neurology 11: 283–292.

Nelson KB (2007) Perinatal Ischemic Stroke. Stroke 38: 742–745.

Paneth N, Rudelli R, Kazam E and Monte W (1994) Brain Damage in the Preterm Infant. London, UK: MacKeith Press.

Rezaie P and Dean A (2002b) Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology 22: 106–132.

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Feather‐Schussler, Danielle, and Ferguson, Tanya S(Mar 2015) Cerebral Palsy: Underlying Causes and Animal Models. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025849]