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Hypothermia is not neuroprotective after infection-sensitized neonatal hypoxicischemic brain injury
Osredkar, Damjan ...
BackgroundTherapeutic hypothermia (HT) is the standard treatment after perinatal hypoxicischemic (HI) injury. Infection increases vulnerability to HI injury, but the effect of HT on ...lipopolysaccharide (LPS) sensitized HI brain injury is unknown.Design/methodsP7 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.ResultsMean 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.ConclusionsTherapeutic 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.
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