在大鼠长时间梭曼诱导癫痫持续状态后，常驻脑细胞中趋化因子 CXCL1 和 MIP-1α 的表达增加先于中性粒细胞浸润到大脑中。
Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats.
机构信息
Research Division, Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010, USA.
出版信息
J Neuroinflammation. 2011 May 2;8:41. doi: 10.1186/1742-2094-8-41.
BACKGROUND
Exposure to the nerve agent soman (GD) causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE). Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model.
METHODS
Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus) following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells). Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines.
RESULTS
We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain.
CONCLUSIONS
A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.
背景
接触神经毒剂沙林（GD）会导致神经元细胞死亡和行为功能障碍，这取决于癫痫持续状态（SE）的诱导。尽管神经炎症和中性粒细胞浸润是突出的特征，但对于这个病理过程的成熟过程知之甚少。本研究的目的是定量研究早期趋化信号的区域和时间进展，描述这些因子的细胞表达，并使用大鼠 GD 惊厥模型研究损伤大脑中表达与中性粒细胞浸润之间的关系。
方法
使用多重珠免疫分析，在 SE 发作后 72 小时内，在多个脑区（即梨状皮层、海马和丘脑）中定量测定了 4 种负责中性粒细胞浸润和激活的趋化因子的蛋白水平。具有显著增加蛋白水平的趋化因子被定位到驻留脑细胞（即神经元、星形胶质细胞、小胶质细胞和内皮细胞）。最后，量化了这些脑区中的中性粒细胞浸润，并将其与这些趋化因子的表达相关联。
结果
我们观察到 SE 发作后 CXCL1 和 MIP-1α 的浓度显著增加。CXCL1 表达源于神经元和内皮细胞，而 MIP-1α 则由神经元和小胶质细胞表达。最后，这些趋化因子的表达直接先于并与大脑中显著的中性粒细胞浸润呈正相关。这些数据表明，在 GD 诱导的 SE 后，各种脑细胞产生强烈的趋化反应，将循环中的中性粒细胞募集到受损的大脑中。
结论
在 GD 诱导的 SE 后，强烈诱导中性粒细胞趋化因子的产生导致中性粒细胞涌入受损的脑组织。这个过程可能在这个模型中观察到的进行性继发性脑病理中起关键作用，但需要进一步研究。
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