Increased CCL2, CCL3, CCL5, and IL-1β cytokine concentration in piriform cortex, hippocampus, and neocortex after pilocarpine-induced seizures

Journal of Neuroinflammation

Lee A. Shapiro¹  Khurshed Katki¹  Maira L. Foresti²  Gabriel M. Arisi² 

[1] Central Texas Veterans Health Care System, Temple 76504, TX, USA;Present address: Department of Physiology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, Lab 3A, São Paulo 04039-032, SP, Brazil

关键词: Multiplex;    Inflammation;    Seizure;    Epilepsy;    Interleukin;    Cytokine;    Chemokine;   

Others  :  1221939
DOI  :  10.1186/s12974-015-0347-z

 received in 2014-12-02, accepted in 2015-06-17,  发布年份 2015

【 摘 要 】

Background

Cytokines and chemokines play an important role in the neuroinflammatory response to an initial precipitating injury such as status epilepticus (SE). These signaling molecules participate in recruitment of immune cells, including brain macrophages (microglia), as well as neuroplastic changes, deterioration of damaged tissue, and epileptogenesis. This study describes the temporal and brain region pattern expression of numerous cytokines, including chemokines, after pilocarpine-induced seizures and discusses them in the larger context of their potential involvement in the changes that precede the development of epilepsy.

Findings

Adult rats received pilocarpine to induce SE and 90 min after seizure onset were treated with diazepam to mitigate seizures. Rats were subsequently deeply anesthetized and brain regions (hippocampus, piriform cortex, neocortex, and cerebellum) were freshly dissected at 2, 6, and 24 h or 5 days after seizures. Using methodology identical to our previous studies, simultaneous assay of multiple cytokines (CCL2, CCL3, CCL5, interleukin IL-1β, tumor necrosis factor (TNF-α)), and vascular endothelial growth factor (VEGF) was performed and compared to control rats. These proteins were selected based on existing evidence implicating them in the epileptogenic progression. A robust increase in CCL2 and CCL3 concentrations in the hippocampus, piriform cortex, and neocortex was observed at all time-points. The concentrations peaked with a ~200-fold increase 24 h after seizures and were two orders of magnitude greater than the significant increases observed for CCL5 and IL-1β in the same brain structures. TNF-α levels were altered in the piriform cortex and neocortex (24 h) and in the hippocampus (5 days) after SE.

Conclusions

Pilocarpine-induced status epilepticus causes a rapid increase of multiple cytokines in limbic and neocortical regions. Understanding the precise spatial and temporal pattern of cytokines and chemokine changes could provide more viable therapeutic targets to reduce, reverse, or prevent the development of epilepsy following a precipitating injury.

【 授权许可】

   
2015 Arisi et al.

【 图 表 】

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