Failure to sustain recovery of Na,K-ATPase function is a possible mechanism for striatal neurodegeneration in hypoxic-ischemic newborn piglets

Hypoxia-ischemia (HI) in the newborn can lead to a variety of sensorimotor abnormalities, including movement and posture disorders. Striatal neurons u ndergo necrosis after M in piglets, but mechanisms for this neuronal death are not understood. mie tested the hypothesis that Na,K-ATPase is defective in striatum early after HI. Piglets (1 week old) were subjected to 30 min hypoxia (arterial oxygen saturation 30%) and then 7 min of airway occlusion (oxygen saturation 5%), producing asphyxic cardiac arrest. Animals were re suscitated and recovered for 3, 6, 12, and 24 h, respectively. Neuronal nec rosis in the striatum is progressive [14]. Na,K-ATPase activity (percent of control) was 60, 98, 51, and 54% at 3, 6, 12, and 24 h after KI, respectiv ely. Intrastriatal differences in enzyme activity were detected histochemic ally, with the putamen showing greater loss of Na,K-ATPase activity than ca udate after 12 h recovery. Immunoblotting showed that the levels of the alp ha (3) isoform (localized exclusively to neurons) were 85, 115, 101: and 79 % of sham control at 3, 6, 12, and 24 h, respectively. Levels of beta (1), the predominant beta isoform, were similar to alpha (3), while levels of th e alpha (1) subunit, the catalytic isoform found in neurons and glia, were 182, 179, 226, and 153% at the same recovery times. We conclude that early inactivation of Na,K-ATPase function participates in the pathogenesis of st riatal neuron necrosis, but that loss of enzyme function early after HI is not caused by depletion of composite alpha/beta subunits. (C) 2001 Elsevier Science B.V: All rights reserved.