Animal Models of Cerebral Palsy: What Can We Learn About Cerebral Palsy in Humans

Abstract

Cerebral palsy (CP) is caused by nonprogressive neurological damage and manifested by disordered movement and posture, which leads to motor dysfunction. Two of the known etiologies of CP are perinatal asphyxia and prenatal/perinatal infection. Attempts to better understand the etiology and pathogenesis of CP have brought many investigators to develop animal models that mimic human CP. Mice and rats were extensively used but they have several disadvantages: due to short gestation, the brain at delivery is very immature and therefore most models are of young postnatal animals whose brains are at the developmental stage of the third trimester human fetus. Postnatal young mice and rat offspring are subjected to hypoxia/ ischemia or infection/inflammation or a combination of the two. The clinical presentation is different compared to human CP, and there is a tendency for spontaneous recovery. Rabbits have a longer gestation and the injuries can be produced during the last week of pregnancy. Yet, the clinical picture of the induced brain damage is different from that in humans, and here too, there is a tendency for spontaneous recovery. Sheep have a relatively long gestation and the different models more closely resemble human CP. Nonhuman primates show similar nonprogressive motor impairment following either hypoxia/ischemia or infection/inflammation. The extent of the brain damage and the clinical findings are similar to human CP with similar neuropathological brain findings and with good possibilities to assess a variety of treatment modalities. We conclude that the animal model of CP should be chosen according to the aims of the study.