CREATINE PROTECTS THE CENTRAL RESPIRATORY NETWORK OF MAMMALS UNDER ANOXIC CONDITIONS

The effect of creatine (Cr) on the response of the respiratory center to anoxia was analyzed at different postnatal stages in a brainstem sl ice preparation of mice. Spontaneous rhythmic activity was recorded fr om hypoglossal rootlets (XII) and from identified neurons within the p reBotzinger complex using the whole cell patch clamp technique. The hy poxic response was evaluated in slices from animals (n = 46), which re ceived normal nutrition (controls, n = 16), from litters of animals fe d with Cr (2 g/kg/day; nutrition group, n = 8), or after incubating sl ices for 3 h in Cr (200 mu M) (incubation group, n = 22). ATP was meas ured in slices from controls and Cr-incubated slices which underwent 3 0-min anoxia. In neonatal animals (P0-5), amplitudes of hypoglossal bu rsts increased initially during anoxia by 14% in controls and by 41% i n Cr-supplemented animals when compared with preanoxic values. Hypoglo ssal burst duration increased by 3% in controls, but by 18% in the Cr- nutrition group. In brainstem slices, the initial increase of amplitud es changed from 14% (controls) to 59% (Cr incubation) and prolongation of bursts from 3% (controls) to 37% (Cr incubation) compared with pre anoxic values. In juvenile controls (P6-13), burst amplitude and durat ion increased by 12 and 14% during early anoxia when referred to prean oxic values. In slices from Cr-pretreated animals, increases of 48% (a mplitude) and 21% (burst duration) occurred. The ATP levels remained c onstant during a 30-min anoxic period in the Cr-pretreated group compa red with a decrease of 44% in slices from controls. Our data suggest t hat Cr can ameliorate hypoxic energy failure. Further studies will exa mine the neuroprotective potential in humans.