Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxic-ischemic brain injury

Background: Therapeutic hypothermia (HT) is the standard treatment after perinatal hypoxic-ischemic (HI) injury. Infection increases vulnerability to HI injury, but the effect of HT on lipopolysaccharide (LPS) sensitized HI brain injury is unknown. Design/methods: P7 rat pups were injected either with vehicle or LPS, and after a 4 h delay they were exposed to left carotid ligation followed by global hypoxia inducing a unilateral stroke-like HI injury. Pups were randomized to the following treatments: (1) vehicle treated HI-pups receiving normothermia treatment (NT) (Veh-NT; n = 30); (2) LPS treated HI-pups receiving NT treatment (LPS-NT; n = 35); (3) vehicle treated HI-pups receiving HT treatment (Veh-HT; n = 29); or (4) LPS treated HI-pups receiving HT treatment (LPS-HT; n = 46). Relative area loss of the left/right hemisphere and the areas of hippocampi were measured at P14. Results: Mean brain area loss in the Veh-NT group was 11.2 +/- 14%. The brain area loss in LPS-NT pups was 29.8 +/- 17%, which was significantly higher than in the Veh-NT group (p = 0.002). The Veh-HT group had a significantly smaller brain area loss (5.4 +/- 6%), when compared to Veh-NT group (p = 0.043). The LPS-HT group showed a brain area loss of 32.5 +/- 16%, which was significantly higher than in the Veh-HT group (p < 0.001). LPS-HT group also had significantly smaller size of the left hippocampus, which was not found in other groups. LPS-sensitization significantly decreased the sizes of the right, unligated-hemispheres, independent of post-HI treatment. Conclusions: Therapeutic hypothermia is not neuroprotective in this LPS-sensitized unilateral stroke-like HI brain injury model in newborn rats. Lack of neuroprotection was particularly seen in the hippocampus. Pre-insult exposure to LPS also induced brain area loss in the unligated hemisphere, which is normally not affected in this model. (C) 2014 Elsevier Ireland Ltd. All rights reserved.