Hypoxic-Ischemic Encephalopathy occurs in two phases. Primary injury: ATP depletion leads to failure of Na/K ATPase, intracellular calcium influx, and excitotoxic glutamate release. Latent period (6-hour therapeutic window): partial energy recovery. Secondary injury: mitochondrial failure, ROS production, inflammation (IL-1beta, TNF-alpha), and apoptosis via caspase activation. Therapeutic hypothermia (33.5C for 72 hours) reduces metabolic rate by 5% per degree, decreases excitotoxicity, and inhibits apoptotic pathways.