Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats

Journal of Neuroinflammation

Shyam S Mohapatra¹  Subhra Mohapatra¹  Keith R Pennypacker³  Saniya Rangooni²  Christopher C Leonardo³  Mahasweta Das² 

[1] JAH-VA Hospital, Tampa, FL, 13000 Bruce B. Downs Blvd. Tampa, FL 33612, USA;Department of Internal Medicine, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA;Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA

关键词: hippocampus;    cortex;    spleen;    neural damage;    inflammation;    CCL20;    LFPI;    TBI;   

Others  :  1213037
DOI  :  10.1186/1742-2094-8-148

 received in 2011-04-12, accepted in 2011-10-31,  发布年份 2011

【 摘 要 】

Background

Traumatic brain injury (TBI) evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics.

Methods

In this report, we used a rat lateral fluid percussion impact (LFPI) model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, polymerase chain reaction (qRT PCR), enzyme linked immunosorbent assay (ELISA) and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues.

Results

Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b⁺ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues.

Conclusion

These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in promoting neuronal injury and central nervous system inflammation in response to mild TBI.

【 授权许可】

   
2011 Das et al; licensee BioMed Central Ltd.

【 图 表 】

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