Addition of low-dose @entity1092 to saline resuscitation provides neuroprotection and improves long-term outcomes in a large animal model of combined @entity131 and XXXX .

@entity1707 @entity131 @entity548 @entity3262 @entity75 @entity1092 @entity16 @entity376
BACKGROUND: Combined @entity131 ( @entity131 ) and @entity548 ( @entity548 ) is highly lethal. In a nonsurvival model of @entity131 + @entity548 , addition of high-dose @entity1092 ( @entity3262 ) (300 mg/kg) to hetastarch reduced @entity75 size and associated swelling 6 hours after injury; whether this would have translated into better neurologic outcomes remains unknown. It is also unclear whether lower doses of @entity3262 would be neuroprotective. We hypothesized that addition of low-dose @entity3262 to normal saline (NS) resuscitation would result in improved long-term neurologic recovery and decreased @entity75 size. METHODS: @entity131 was created in anesthetized @entity1707 (40-43 kg) by controlled cortical impact, and volume-controlled @entity548 (40% volume) was induced concurrently. After 2 hours of shock, animals were randomized (n = 5 per group) to NS (3* shed blood) or NS + @entity3262 (150 mg/kg). Six hours after resuscitation, packed red blood cells were transfused, and animals were recovered. Peripheral blood mononuclear cells were analyzed for acetylated histone-H3 at @entity376 -9. A Neurological Severity Score (NSS) was assessed daily for 30 days. Brain magnetic resonance imaging was performed on Days 3 and 10. Cognitive performance was assessed by training animals to retrieve food from color-coded boxes. RESULTS: There was a significant increase in histone acetylation in the NS + @entity3262 -treated animals compared with NS treatment. The NS + @entity3262 group demonstrated significantly decreased @entity16 and faster speed of recovery as well as smaller @entity75 size compared with the NS group. Although the final cognitive function scores were similar between the groups, the @entity3262 -treated animals reached the goal significantly faster than the NS controls. CONCLUSION: In this long-term survival model of @entity131 + @entity548 , addition of low-dose @entity3262 to saline resuscitation resulted in attenuated @entity16 , faster neurologic recovery, smaller @entity75 size, and a quicker normalization of cognitive functions.
