Abstract
Trauma patients who suffer cardiac arrest (CA) from exsanguination rarely survive.
Emergency preservation and resuscitation using hypothermia was developed to buy time
for resuscitative surgery and delayed resuscitation with cardiopulmonary bypass (CPB),
but intact survival is limited by neuronal death associated with microglial proliferation
and activation. Pharmacological modulation of microglia may improve outcome following
CA. Systemic injection of liposome-encapsulated clodronate (LEC) depletes macrophages.
To test the hypothesis that intrahippocampal injection of LEC would attenuate local
microglial proliferation after CA in rats, we administered LEC or PBS into the right
or left hippocampus, respectively. After rapid exsanguination and 6 min no-flow, hypothermia was induced by ice-cold (IC) or room-temperature (RT) flush.
Total duration of CA was 20 min. Pre-treatment (IC, RTpre) and post-treatment (RTpost) groups were studied, along
with shams (cannulation only) and CPB controls. On day 7, shams and CPB groups showed
neither neuronal death nor microglial activation. In contrast, the number of microglia
in hippocampus in each individual group (IC, RTpre, RTpost) was decreased with LEC
vs. PBS by ∼34–46% (P < 0.05). Microglial proliferation was attenuated in the IC vs. RT groups (P < 0.05). Neuronal death did not differ between hemispheres or IC vs. RT groups. Thus,
intrahippocampal injection of LEC attenuated microglial proliferation by ∼40%, but
did not alter neuronal death. This suggests that microglia may not play a pivotal
role in mediating neuronal death in prolonged hypothermic CA. This novel strategy
provides us with a tool to study the specific effects of microglia in hypothermic
CA.
Keywords
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Article info
Publication history
Published online: October 04, 2011
Accepted:
September 12,
2011
Received in revised form:
September 1,
2011
Received:
August 17,
2010
Footnotes
☆A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2011.09.016.
Identification
Copyright
© 2011 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
