PMID- 23694871
OWN - NLM
STAT- MEDLINE
DCOM- 20130722
LR  - 20130925
IS  - 2163-0763 (Electronic)
IS  - 2163-0755 (Linking)
VI  - 74
IP  - 6
DP  - 2013 Jun
TI  - Immediate splenectomy down-regulates the MAPK-NF-kappaB signaling pathway in rat 
      brain after severe traumatic brain injury.
PG  - 1446-53
LID - 10.1097/TA.0b013e31829246ad [doi]
AB  - BACKGROUND: The treatment of severe traumatic brain injury (TBI) remains a 
      difficult process. One key to improving treatment efficacy is to reduce secondary 
      brain injury. Local and systemic inflammatory responses play an important role in 
      secondary injury after TBI, which if unchecked can lead to fatal cerebral edema. 
      Previous studies focused mainly on local brain tissue, whereas little is known 
      about the contribution of peripheral organs in the pathogenesis of TBI. We 
      previously showed that immediate splenectomy decreases mortality and improves 
      cognitive function in rats after severe TBI by inhibiting the release of 
      proinflammatory cytokines both systematically and locally in the injured brain. 
      In this study, we further investigated the molecular mechanisms responsible for 
      the effect of the spleen on local brain inflammation after TBI. METHODS: We 
      established a severe TBI model with rats and performed splenectomy to study the 
      effect of the spleen on mitogen-activated protein kinase (MAPK)-NF-kappaB activation 
      in the brain tissue. The expression of p38 MAPK, extracellular regulated protein 
      kinases (ERK), and NF-kappaB protein in the trauma region was examined by Western 
      blotting. The neuron-like PC-12 cell line and microglia-like BV-2 cell line were 
      used for in vitro experiments to test the effects of spleen supernatant after 
      TBI. Cell apoptosis (annexin V/propidium iodide staining), NF-kappaB nuclear 
      translocation (immunofluorescence microscopy), and MAPK signaling 
      (phosphorylation of p-p38 and p-ERK) were examined. RESULTS: We found that TBI 
      significantly up-regulated MAPK signaling in the injured brain region, whereas 
      immediate splenectomy suppressed MAPK activation. In vitro, the spleen 
      supernatant from rats after TBI also resulted in increased MAPK activation and 
      NF-kappaB nuclear translocation in microglia-like BV-2 cells, whereas the application 
      of interleukin (IL)-1R antagonist (IL-1Ra) significantly reduced the expression 
      of p-p38 and p-ERK as well as NF-kappaB nuclear translocation. In addition, spleen 
      supernatant after TBI induced apoptosis in neuron-like PC-12 cells, and IL-1Ra 
      could effectively reduce apoptosis. CONCLUSION: Our study demonstrates that 
      immediate splenectomy down-regulates the MAPK-NF-kappaB signaling pathway in rat 
      brain after severe TBI. We also provide experimental evidence for the potential 
      use of IL-1Ra to alleviate brain inflammation after TBI.
FAU - Chu, Weihua
AU  - Chu W
AD  - Department of Neurosurgery, Southwest Hospital, Third Military Medical 
      University, Chongqing, 400038, China.
FAU - Li, Mei
AU  - Li M
FAU - Li, Fei
AU  - Li F
FAU - Hu, Rong
AU  - Hu R
FAU - Chen, Zhi
AU  - Chen Z
FAU - Lin, Jiangkai
AU  - Lin J
FAU - Feng, Hua
AU  - Feng H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Trauma Acute Care Surg
JT  - The journal of trauma and acute care surgery
JID - 101570622
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blotting, Western
MH  - Brain/*physiopathology
MH  - Brain Injuries/*physiopathology/surgery
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - MAP Kinase Signaling System/*physiology
MH  - Male
MH  - NF-kappa B/*physiology
MH  - PC12 Cells
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spleen/physiopathology
MH  - *Splenectomy
EDAT- 2013/05/23 06:00
MHDA- 2013/07/23 06:00
CRDT- 2013/05/23 06:00
PHST- 2013/05/23 06:00 [entrez]
PHST- 2013/05/23 06:00 [pubmed]
PHST- 2013/07/23 06:00 [medline]
AID - 01586154-201306000-00010 [pii]
AID - 10.1097/TA.0b013e31829246ad [doi]
PST - ppublish
SO  - J Trauma Acute Care Surg. 2013 Jun;74(6):1446-53. doi: 
      10.1097/TA.0b013e31829246ad.