Pathophysiology and neuroprotection of global and focal perinatal brain injury:lessons from animal models

BACKGROUND: Arterial ischemic stroke occurs more frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared with childhood. This concept was recently challenged by clinical studies showing marked motor disabilities after stroke in neonates, with the severity of motor and cortical sensory deficits similar in both perinatal and childhood ischemic stroke. Our understanding of the triggers and the pathophysiological mechanisms of perinatal stroke has greatly improved in recent years, but many factors remain incompletely understood.METHODS: In this review, we focus on the pathophysiology of perinatal stroke and on therapeutic strategies that can protect the immature brain from the consequences of stroke by targeting inflammation and brain microenvironment.RESULTS: Studies in neonatal rodent models of cerebral ischemia have suggested a potential role for soluble inflammatory molecules as important modulators of injury and recovery. A great effort is underway to investigate neuroprotective molecules based on our increasing understanding of the pathophysiology.CONCLUSION: In this review, we provide a comprehensive summary of new insights concerning pathophysiology of focal and global perinatal brain injury and their implications for new therapeutic approaches.