Different TLR4 expression and microglia/macrophage activation induced by hemorrhage in the rat spinal cord after compressive injury
Open Access
- 10 September 2013
- journal article
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 10 (1), 112
- https://doi.org/10.1186/1742-2094-10-112
Abstract
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.Keywords
This publication has 47 references indexed in Scilit:
- Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhageJournal of Neuroinflammation, 2012
- Early Blockade of TLRs MyD88-Dependent Pathway May Reduce Secondary Spinal Cord Injury in the RatsEvidence-Based Complementary and Alternative Medicine, 2012
- TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's diseaseJournal of Neuroinflammation, 2011
- Toll‐like receptor 4 contributes to poor outcome after intracerebral hemorrhageAnnals of Neurology, 2011
- Beneficial Effect of the Traditional Chinese Drug Shu-Xue-Tong on Recovery of Spinal Cord Injury in the RatEvidence-Based Complementary and Alternative Medicine, 2011
- Progesterone Administration Modulates Cortical TLR4/NF-κB Signaling Pathway after Subarachnoid Hemorrhage in Male RatsMediators of Inflammation, 2011
- The Regulation of the CNS Innate Immune Response Is Vital for the Restoration of Tissue Homeostasis (Repair) after Acute Brain Injury: A Brief ReviewInternational Journal of Inflammation, 2010
- Activation of TLR4-Mediated NFB Signaling in Hemorrhagic Brain in RatsMediators of Inflammation, 2009
- Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathwayJournal of Neuroinflammation, 2008
- Activation of Toll-like receptor 4 signaling contributes to hippocampal neuronal death following global cerebral ischemia/reperfusionJournal of Neuroimmunology, 2007