Abstract 15: Minocycline Attenuates Brain Tissue Levels of TNFα After Prolonged Hypothermic Cardiac Arrest in Rats
Background: Neuro-cognitive disabilities are a well recognized complication of hypothermic circulatory arrest. We and others have reported that prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation and activation that are only partially mitigated by hypothermia. Microglia elaborate tumor necrosis factor alpha (TNFa) which exacerbates edema and injury after CNS insults. Minocycline is neuroprotective in some brain ischemia models in part by blunting the microglial response. We tested the hypothesis that minocycline would attenuate neuroinflammation as reflected by brain tissue levels of TNFa after hypothermic CA in rats.
Methods: Rats were subjected to rapid exsanguination over 5 min, followed by a 6 min normothermic CA. Hypothermia (30 C) was then induced by a one-way aortic saline flush. After a total of 20 min CA, resuscitation was achieved via cardiopulmonary bypass (CPB) over 60 min. After 5 min reperfusion, minocycline (90 mg/kg; n=6) or vehicle (PBS; n=6) were given. Hypothermia (34 C) was maintained for 6 h. Rats were then sacrificed and TNFa was quantified (ELISA) in four brain regions (cerebellum, CEREB; cortex, CTX; hippocampus, HIP; striatum, STRI). Naïve rats (n=6) and rats subjected to 60 min CPB served as controls (n=6).
Results: Naïve rats and CPB controls had no detectable TNFa in any brain region. CA markedly increased brain TNFa. Regional differences were seen, with the highest TNFa levels in striatum in each group (P<0.05 vs. all other brain regions). Minocycline attenuated TNFa levels in CTX, HIP and STRI (Fig).
Discussion: We report region-dependent increases in brain TNFa levels after prolonged hypothermic CA, with maximal increases in striatum. That minocycline decreased brain TNFa levels suggests that it may represent a therapeutic adjunct to hypothermia in CA neuroprotection.
- © 2011 by American Heart Association, Inc.