Inhaled 45 50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia
Cooling to 33.5 degC in babies with neonatal encephalopathy significantly reduces death and disability, however additional therapies are needed to maximize brain protection. Following hypoxia ischemia we assessed whether inhaled 45 50% Argon from 2 26 h augmented hypothermia neuroprotection in a neonatal piglet model, using MRS and aEEG, which predict outcome in babies with neonatal encephalopathy, and immunohistochemistry. Following cerebral hypoxia ischemia, 20 Newborn male Large White piglets 40 h were randomized to: (i) Cooling (33 degC) from 2 26 h (n 10) or (ii) Cooling and inhaled 45 50% Argon (Cooling Argon) from 2 26 h (n 8) Whole brain phosphorus 31 and regional proton MRS were acquired at baseline, 24 and 48 h after hypoxia ischemia. EEG was monitored. At 48 h after hypoxia ischemia, cell death (TUNEL) was evaluated over 7 brain regions. There were no differences in body weight, duration of hypoxia ischemia or insult severity; throughout the study there were no differences in heart rate, arterial blood pressure, blood biochemistry and inotrope support. Two piglets in the Cooling Argon group were excluded. Comparing Cooling Argon with Cooling there was preservation of whole brain MRS ATP and PCr/Pi at 48 h after hypoxia ischemia (p 0.001 for both) and lower 1H MRS lactate/N acetyl aspartate in white (p 0.03 and 0.04) but not gray matter at 24 and 48 h. EEG background recovery was faster (p 0.01) with Cooling Argon. An overall difference between average cell death of Cooling versus Cooling Argon was observed (p 0.01) estimated cells per mm2 were 23.9 points lower (95% C.I. 7.3 40.5) for the Cooling Argon versus Cooling. Inhaled 45 50% Argon from 2 26 h augmented hypothermic protection at 48 h after hypoxia ischemia shown by improved brain energy metabolism on MRS, faster EEG recovery and reduced cell death on TUNEL. Argon may provide a cheap and practical therapy to augment cooling for neonatal encephalopathy.
Neurobiology of Disease