Journal
BRAIN RESEARCH
Volume 1502, Issue -, Pages 1-10Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2013.01.037
Keywords
Lipoxin A(4); Traumatic brain injury; Blood-brain barrier; Brain edema; Pro-inflammatory cytokines; Mitogen-activated protein kinases
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Funding
- National Science Foundation of China [81271379, 81172911, 81172897]
- Shanghai Forensic Key Laboratory Foundation [KF1005]
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The present study was designed to investigate the effects of lipoxin A(4) (LXA(4)) on traumatic brain injury (TBI) and to analyze the possible mechanism. Outcome parameters consist of blood-brain barrier (BBB) breakdown, brain edema and lesion volume. Using western blot and quantitative real-time PCR, we examined the levels of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and activation of mitogen-activated protein kinases (MAPKs) (including ERK, JNK, p38) following TBI. To investigate the cell types in which the LXA(4) receptor (ALXR) staining was localized, brain sections pulsed with ALXR were subjected to immunofluorescence staining with antibodies against cell type-specific antigens. Our findings show that LXA(4) decreases BBB permeability, attenuates brain edema, and reduces TBI-induced lesion volume. In addition, LXA(4) inhibits TBI-induced elevation of mRNA and protein levels of pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6). In the injured cortex at 24 h post-TBI, the phosphorylated-ERK (p-ERK) and -JNK (p-JNK), but not -p38 (p-p38) levels were increased. The p-ERK and p-JNK production were attenuated by their respective inhibitors (PD98059 and SP600125), as well as LXA(4). Moreover, ALXR was found to label more GFAP positive cells, whereas few CD11b-positive cells were labeled by ALXR within the layers of the injured cortex at 24 h post-TBI. The activation of ALXR in astrocytes was partially enhanced by LXA(4) treatment. Taken together, these data indicate that TBI activates pro-inflammatory cytokines, the MAPK pathways together with ALXR in astrocytes, and these mechanisms may be exploited by pharmacological interventions. (C) 2013 Elsevier B.V. All rights reserved.
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