Models of cerebral palsy: Which ones are best?

The workshops brought together examples of innovative work on experimental models of cerebral palsy to asses their strengths and weaknesses and to ask which are most relevant to reducing the impact of the disorder on children. As discussed above and in the articles in this issue, all of the models have certain drawbacks, yet each has important strengths. None of them stand out as the best, and data from several models need to be combined like the pieces of a puzzle to make a complete picture. If one important criterion for experimental models is how well they lead to clinical therapies, the models of asphyxia in the term infant are showing promise at the moment. The use of rodent, ovine, and piglet models of asphyxia developed over the last 25 years has validated the concept of the delayed cascade of injury after asphyxia and the hypothesis that hypothermia might interrupt it. If hypothermia proves to be a useful therapy to reduce death and reserve disability in term infants, as recent preliminary report suggest, it will be a step forward and a validation of these models. Another promising area seems to be white-matter injury in preterm infants, with the focus on inflamation and injury to oligodendrocytes mediated by glutamate. With at least one possible glutamate antagonist drug already available clinically and showing some protective action in rodent models, this should be an active area in the future. The area of inflammation is also of great importance from the standpoint of both cerebral palsy and understanding the initiation of premature labor. The mechanism for the gray-matter impairment associated with white-matter injury in premature infants is also of great importance. In summary, we concluded from the workshop that although there are no truly outstanding models, there are a number of good established ones, as well as some promising new ones. They are likely to drive progress in this area over the next few years.