PROTECTIVE ACTIONS OF PJ34, A POLY(ADP-RIBOSE)POLYMERASE INHIBITOR, ON THE BLOOD-BRAIN BARRIER AFTER TRAUMATIC BRAIN INJURY IN MICE
First author:Xiaogang Tao
Corresponding author:B Liu
2015-04-16
Journal:Neuroscience
Publication type: Research
IF(IF): 3.59
PMID: 25668593 Link To Pubmed Full text Download
N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide (PJ34) (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally at 5 min and 8 h after experimental CCI. After 6 h and 24 h of CCI, the permeability of the cortical BBB was determined after Evans Blue administration. The water content of the brain was also measured. Treatment with PJ34 markedly attenuated the permeability of the BBB and decreased the brain edema at 6 h and 24 h after CCI.
These data suggest the protective effects of PJ34 on BBB integrity and cell death during acute TBI.
Our data showed the up-regulation of nuclear factor-κB in cytosolic fractions and nuclear fractions in the injured cortex, and these changes were reversed by PJ34. Moreover, PJ34 significantly lessened the activities of myeloperoxidase and the levels of matrix metalloproteinase-9, enhanced the levels of occludin, laminin, collagen IV and integrin β1, reduced neurological deficits, decreased the contusion volume, and attenuated the necrotic and apoptotic neuronal cell death.