Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets

Journal of Neuroinflammation

William F Hickey¹  Beth A Costine²  David J Graber¹ 

[1] Department of Pathology, Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon 03756, NH, USA;Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston 02114, MA, USA

关键词: Slice;    Prostaglandin-endoperoxide synthase-2;    Pig;    Mouse;    Injury;    Chemokines;    Cerebral cortex;    Cytokines;   

Others  :  1227092
DOI  :  10.1186/s12974-015-0298-4

 received in 2014-10-28, accepted in 2015-04-09,  发布年份 2015

【 摘 要 】

Background

The immunological response during the first 24 hours after traumatic brain injury (TBI) may be a critical therapeutic interval for limiting the secondary neuronal damage that is influenced by enhanced inflammatory mediator expression.

Methods

To gain further insight of the early injury response, we examined the expression of several inflammatory genes by real-time qPCR as a function of time or distance from injury in two distinct mammalian models: an ex vivo mouse cortical slice injury system and an in vivo piglet model of brain injury.

Results

Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical slices. Chemokine and PTGS2 mRNAs remained elevated in slices at 24 h, whereas IL-1β and TNF-α expressions decreased from earlier peak levels. At 24 h after cortical injury in 1-month-old piglets, the expression of CCL2 mRNA was significantly increased in the lesion core and in the penumbra region. The expression of PTGS2, IL-1β, and TNF-α was variable among the piglets.

Conclusions

These in vitro and large animal models of cortical injury expand our understanding of the early timing and spread of the immunological response and can serve as preclinical systems to facilitate the discovery of therapeutic agents for TBI aimed at regulating inflammatory mediator expression.

【 授权许可】

   
2015 Graber et al.; licensee BioMed Central.

【 图 表 】

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