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Spine (Phila Pa 1976). 2010 May 15;35(11):1109-15. doi: 10.1097/BRS.0b013e3181bd14b6.

High mobility group box 1 is upregulated after spinal cord injury and is associated with neuronal cell apoptosis.

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1
Department of Orthopaedic Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.

Abstract

STUDY DESIGN:

Cerebrocortical culture and rat spinal cord injury (SCI) model were used to examine the expression of high mobility group box 1 (HMGB1), TNF-alpha, and Rage by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical examination. In addition, relationship between upregulation of HMGB1 and neural cells apoptosis was evaluated after SCI.

OBJECTIVE:

To evaluate the upregulation of HMGB1, TNF-alpha, and Rage after SCI.

SUMMARY OF BACKGROUND DATA:

It is known that the mode of delayed neuronal cell death after SCI is apoptosis. Apoptotic cell death is influenced by several injury-promoting factors which include pro-inflammatory cytokines. Inhibition of apoptosis promotes neurologic improvement following SCI. However, the factors which transmit inflammatory signaling following SCI have not yet been clarified in detail. HMGB1 was reported as an important mediator of inflammation. We examined the expression of HMGB1, TNF-alpha and Rage following acute SCI.

METHODS:

Expression of HMGB1, TNF-alpha and Rage was examined by RT-PCR and immunohistochemical examination. Apoptotic cell death was evaluated by TUNEL methods.

RESULTS:

HMGB1 was exported from nuclei to cytoplasm in active caspase-3 positive apoptotic cell in vitro. In addition, HMGB1, TNF-alpha, and Rage was expressed in same cell after NMDA treatment. RT-PCR revealed that expression of HMGB1 and TNF-alpha was upregulated following SCI. Immunohistochemical examination revealed that the numbers of HMGB1-, TNF-alpha-, and Rage-positive cells were increased following SCI. The number of TUNEL-positive cells was significantly increased at 12 hours after injury, and was maximal at 72 hours after injury. However, HMGB1- and TNF-alpha-positive cells were maximal in number 48 hours after injury, while Rage-positive cells were maximal in number at 24 hours after injury. These data suggest that HMGB1, TNF-alpha, and Rage were upregulated following SCI but preceding the apoptotic cell death.

CONCLUSION:

Our findings suggest that HMGB1 play a role in the induction of apoptosis via inflammatory reaction.

PMID:
20195207
DOI:
10.1097/BRS.0b013e3181bd14b6
[Indexed for MEDLINE]
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