118 Delayed Hypoyhermia is Neuroprotective in Moderate, but not Severe, Perinatal Hypoxic-Ischaemic Brain Injury

Abstract

Background: Hypothermic neuronal rescue therapy is a potent treatment for the newborn infant with hypoxic-ischaemic (HI) brain injury; the degree of neuroprotection, however, may be dependent on the delay, duration and depth of hypothermia and on the severity of the HI injury. A precise definition of the patient group who will respond to neuroprotective intervention is urgently required.Objective: The purpose of this study was to assess the relationship between the severity of the HI insult and the efficacy of hypothermic neuroprotection assessed histologically in an experimental model.Design/Methods: 19 piglets were randomised to 3 groups within 24 hr of birth; (i) normothermic (n-HI, n= 6); (ii) core temperature 35°C (35-HI n= 6); and (iii) core temperature 33°C (33-HI n= 7). Animals were then subjected to a transient HI insult (bilateral carotid occlusion and FiO2 12–16% for approximately 1 hr). Phosphorus magnetic resonance spectroscopy gave a measure of the duration and magnitude of acute depletion of nucleotide triphosphate (NTP) relative to the exchangeable high energy phosphate pool (EPP): Animals were subgrouped: (i) moderate insult (n-HI-m, 35-HI-m, 33-HI-m); and (ii) severe insult (n-HI-s, 35-HI-s, 33-HI-s). Animals were maintained at target temperature for 24hr commencing 2hr after the end of the insult and then rendered normothermic. At 48hr the animal was sacrificed and the brain perfusion fixed. Hematoxylin and eosin stained slices were assessed in 10 regions in the cortex and 6 regions in the deep grey matter. Percentages of viable and necrotic neurons in each region were compared in subgroups.Results: Consolidating all grades of HI insult, compared to the n-HI group, 33-HI and 35-HI animals both had less dead neurons; only the 33-HI group had more viable neurons (Fig 1, all p< 0.05). In the normothermic group histological scores were similar in moderate and severe insults (Fig 2). Hypothermic intervention improved histological scores in the moderate insult groups (35-HI-m, 33-HI-m) but not in the severe insult groups (Fig 2).Conclusion: These data suggest that HI insult severity affects the efficacy of subsequent hypothermic intervention; systemic hypothermia of 35°C and 33°C were neuroprotective only after moderate HI insults.