Different TLR4 expression and microglia/macrophage activation induced by hemorrhage in the rat spinal cord after compressive injury

Journal of Neuroinflammation

Fang Kuang³  Gong Ju³  Ling Liu³  Peng Cheng³  An-Hui Yao³  Hong Fan³  Zheng-Wu Peng⁴  Jin-Tao Liu²  Yu-Kai Zhang¹ 

[1] Department of Neurosurgery, The 208th Hospital of PLA, Changchun 130011, China;School of Stomatology, Fourth Military Medical University, Xi’an 710032, China;Institute of Neurosciences, Fourth Military Medical University, Xi’an 710032, China;Department of Psychosomatic Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China

关键词: Rat;    Blood-spinal cord barrier;    Spinal cord injury;    Microglia/macrophage;    Toll-like receptor 4;    Hemorrhage;   

Others  :  1152132
DOI  :  10.1186/1742-2094-10-112

 received in 2013-03-22, accepted in 2013-08-30,  发布年份 2013

【 摘 要 】

Background

Hemorrhage is a direct consequence of traumatic injury to the central nervous system and may cause innate immune reactions including cerebral Toll-like receptor (TLR) 4 upregulation which usually leads to poor outcome in the traumatic brain injury. In spinal cord injury (SCI), however, how hemorrhage induces innate immune reaction in spinal parenchyma remains unknown. The present study aimed to see whether blood component and/or other factor(s) induce TLR4 and microglia/macrophages involved innate immune reactions in the rat spinal cord after traumatic injury.

Methods

Using the compressive SCI model of the rat, hemorrhage in the spinal cord was identified by hematoxylin-eosin staining. Microglia/macrophage activation, TLR4 expression, and cell apoptosis were investigated by immunohistochemistry. Nuclear factor (NF)-κB p50 level of the two segments of the cord was detected by western blotting assay. With carbon powder injection, blood origination of the hematoma was explored. The blood-spinal cord barrier (BSCB) states of the lesion site and the hematoma were compared with immunohistochemistry and tannic acid-ferric chloride staining.

Results

Histological observation found blood accumulated in the center of compression lesion site (epicenter) and in the hematoma approximately 1.5 cm away from the epicenter. TLR4 expression, microglia//macrophage activation, and subsequent apoptosis in the area of far-away hematoma were late and weak in comparison to that in epicenter. In addition, TLR4 positive microglia/macrophages appeared to be phagocytotic in the far-away hematoma more obviously than that in the epicenter. Injected carbon powder indicated that accumulated blood of the far-away hematoma originated from the bleeding of the lesion epicenter, and the BSCB around the hematoma was not compromised in the early phase. Accordingly, at 3 days post injury, NF-κB p50 was upregulated based on the similar levels of blood component hemoglobin, and cell apoptosis was obvious in the epicenter but not in the far-away hematoma.

Conclusion

These data suggest that besides blood component, BSCB compromise and the extent of tissue injury contribute more to TLR4 and microglia/macrophage responses to the spinal cord hemorrhage. Therefore, the innate immune environment is a necessary consideration for the SCI therapy targeting TLR4 and microglia/macrophages.

【 授权许可】

   
2013 Zhang et al.; licensee BioMed Central Ltd.

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