Intracisternal Interleukin-1 Receptor Antagonist Prevents Postoperative Cognitive Decline and Neuroinflammatory Response in Aged Rats

被引:208
作者
Barrientos, Ruth M. [1 ]
Hein, Amy M. [1 ]
Frank, Matthew G. [1 ]
Watkins, Linda R. [1 ]
Maier, Steven F. [1 ]
机构
[1] Univ Colorado, Dept Psychol & Neurosci, Ctr Neurosci, Boulder, CO 80309 USA
关键词
PERIPHERAL IMMUNE CHALLENGE; INFLAMMATORY RESPONSE; WORKING-MEMORY; AGING INTERACT; DYSFUNCTION; MICE; INFECTION; DEFICITS; SURGERY; BRAIN;
D O I
10.1523/JNEUROSCI.2173-12.2012
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To investigate the role of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) in postoperative cognitive dysfunction (POCD) in aged rats, we used laparotomy to mimic human abdominal surgery in adult (3 months) and aged (24 months) F344/BN rats. We demonstrated that memory consolidation of the hippocampal-dependent contextual fear-conditioning task is significantly impaired in aged but not young rats 4 d after surgery. Hippocampal-independent auditory-cued fear memory was not disrupted by laparotomy in either age group. The hippocampal-dependent memory impairment was paralleled by elevations of IL-1 beta in the hippocampus of aged animals 1 and 4 d after surgery. These findings support our substantial line of previous research showing that aged animals are more vulnerable to cognitive decline after a peripheral immune challenge. In addition, we demonstrated that a single intracisternal administration of interleukin-1 receptor antagonist (IL-1RA; 112 mu g) at the time of surgery was sufficient to block both the behavioral deficit and the neuroinflammatory response. Injecting the same dose of IL-1RA peripherally failed to have a protective effect. These data provide strong support for the specific role of central, not peripheral, IL-1 beta in POCD. Furthermore, the long-lasting presence of IL-1RA in the brain (4 d) compared with in the blood (<24 h) underscores the value of intracisternal administration of IL-1RA for therapeutic purposes.
引用
收藏
页码:14641 / 14648
页数:8
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