ABSTRACT
During the last 15 years, the etiology of brain injury in human fetuses and neonates has been considered by many to be multifactorial rather than only linked to cardiovascular instability and hypoxia-ischemia (Nelson & Ellenberg, 1996; Evrard, Miladi, Bonnier, & Gressens, 1992; Dammann & Leviton, 1997). Several preconceptional, prenatal, and perinatal factors (like hypoxic-ischemic insults, endocrine imbalances, genetic factors of susceptibility, growth factor deficiency, abnormal competition for growth factors, excess free reactive oxygen species production, maternal infection yielding excess cytokines and other pro-inflammatory agents, exposure to toxins, maternal stress, and so on) have been implicated in the pathophysiology of brain lesions associated with cerebral palsy (Figure 1). Although some of the potentially noxious factors are present in utero and by themselves may cause permanent injury to the developing brain prior to neonatal life, several groups hypothesized that some of these factors act as predisposing factors (“prodamage conditions”), increasing the susceptibility to injury when there is a second unfavorable event (Nelson & Grether, 1998; Dommergues, Patkai, Renauld, Evrard, & Gressens, (2000); Gressens, Rogido, Paindaveine, & Sola, 2002; Dammann, Kuban, & Leviton, 2002; Eklind et al., 2001).
