Protective effects of PARP inhibitor, PJ34, is related to down-regulation of calpain and NF-κB in a mouse model of TBI.
BACKGROUND
Poly(ADP-ribose) polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI).


METHODS
PJ34 (10 mg kg-1), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI. A neurobehavioural evaluation and a histopathological analysis were then performed and the contusion volume, calpain activity and protein levels were measured in all animals.


RESULTS
Treatment with PJ34 markedly reduced neurological deficits, decreased contusion volume and attenuated necrotic and apoptotic neuronal cell death 24 hours after CCI. The data showed that the cytosolic and nuclear fractions of calpain and NF-κB were up-regulated in the injured cortex and that these changes were reversed by PJ34. Moreover, PJ34 significantly enhanced the calpastatin and IκB levels and decreased the levels of inflammatory mediators.


CONCLUSIONS
PARP inhibition by PJ34 suppresses the over-activation of calpain and the production of inflammatory factors that are caused by NF-κB activation and it improves neurological functioning, decreases the contusion volume and attenuates neuronal cell death in a mouse model of CCI.
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Xiaogang
X
Tao
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Xuetao
X
Chen
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Xiang
X
Mao
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Zonggang
Z
Hou
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Shuyu
S
Hao
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.
Runfa
R
Tian
b Department of Neurotrauma, General Hospital of the Armed Police Force , Beijing , PR China.
Zhendan
Z
Zhu
c Department of Neuropharmacology.
Ming
M
Sun
a Department of Neurosurgery, Beijing Tiantan Hospital , Capital Medical University , Beijing , PR China.|b Department of Neurotrauma, General Hospital of the Armed Police Force , Beijing , PR China.|d Department of Neurotrauma , Beijing Neurosurgical Institute, Capital Medical University , Beijing , PR China.|e Nerve Injury and Repair Center of Beijing Institute for Brain Disorders , Beijing , PR China.|f China National Clinical Research Center for Neurological Diseases , Beijing , PR China.|g Beijing Key Laboratory of Central Nervous System Injury , Beijing , PR China.
Baiyun
B
Liu
NF-κB; PARP; calpain; traumatic brain injury