Cerebral Palsy: Underlying Causes and Animal Models

Abstract

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.

A reliable and cost‐effective protocol for creating bilirubin cerebral palsy model in rhesus macaque

“…Cerebral palsy is a group of disorders that affect the central motor and posture development, as well as motion limitations, caused by nonprogressive injuries in the developing fetal or infant brain 1–3 . It occurs in approximately 2–4 out of every 1000 live births worldwide 4,5 . Cerebral palsy is one of the most common severe motor disabilities in childhood, imposing a heavy burden on children, families, and society.…”

“…[1][2][3] It occurs in approximately 2-4 out of every 1000 live births worldwide. 4,5 Cerebral palsy is one of the most common severe motor disabilities in childhood, imposing a heavy burden on children, families, and society.…”

“…[1][2][3] It occurs in approximately 2-4 out of every 1000 live births worldwide. 4,5 Cerebral palsy is one of the most common severe motor disabilities in childhood, imposing a heavy burden on children, families, and society.There are several risk factors associated with cerebral palsy, including hypoxia during pregnancy, intrauterine inflammation/infection, bilirubin encephalopathy, asphyxia at birth, intraventricular hemorrhage, or hypoxic-ischemia. 6 Among these, bilirubin encephalopathy…”

Evaluation of Rhesus Macaque Models for Cerebral Palsy

“…Cerebral palsy (CP) is caused by a non-progressive injury that affects the central nervous system during early development [ 1 , 2 ]. According to the World Health Organization, CP occurs in approximately 2–4 of every 1000 newborns [ 3 ]. CP consists of a set of disorders including postural deficits, motor dysfunctions, and cognitive and mobility difficulties [ 1 , 2 ].…”