Our overarching objective is to understand the underlying mechanisms of perinatal brain injury in particular related to mitochondrial involvement and inflammation. We will seek to understand how inflammation during fetal/neonatal life affects brain development and tunes central nervous system vulnerability to further insults later in life. Based on this knowledge, we hope to develop novel neuroprotective and preventive strategies both for infants suffering from encephalopathy and infants at risk for developing brain injury. We hope to improve the efficacy of hypothermic treatment during the secondary phase of injury through add-on therapies.  There is also a potential possibility to develop treatments that are effective beyond the immediate post-insult period that promote repair and compensatory connectivity during the so-called tertiary phase.