Poloxamer-188 attenuates TBI-induced blood-brain barrier damage leading to decreased brain edema and reduced cellular death.

Abstract

Plasmalemma permeability plays an important role in the secondary neuronal death induced by traumatic brain injury (TBI). Previous works showed that Poloxamer 188 (P188) could restore the intactness of the plasma membrane and play a cytoprotective action. However, the roles of P188 in blood-brain barrier (BBB) integrity and TBI-induced neural cell death are still not clear. In this study, mice were induced TBI by controlled cortical impact (CCI), and cerebral water content was measured to explore the profile of brain edema after CCI. Further, the regimen of P188 in mouse CCI models was optimized. The neurological test and BBB integrity assessment were performed, and the numbers of TBI-induced neural cell death were counted by propidium iodide (PI) labeling. The expression of apoptotic pathway associated proteins (Bax, cyt-c, caspase-8, caspase-9, caspase-3, P53) and aquaporin-4 (AQP4) was assessed by RT-PCR or immunoblotting. The data showed that the brain edema peaked at 24 h after TBI in untreated animals. Tail intravenous injection of P188 (4 mg/ml, 100 μl) 30 min before TBI or within 30 min after TBI could attenuate TBI-induced brain edema. P188 pre-treatment restored BBB integrity, suppressed TBI-induced neural cell death, and improved neurological function. TBI induced an up-regulation of Bax, cyt-c, caspase-8, caspase-9, caspase-3, and the expression of p53 was down-regulated by P188 pre-treatment. AQP4 mainly located on endothelial cells and astrocytes, and its expression was also regulated by P188 pretreatment. All these results revealed that P188 attenuates TBI-induced brain edema by resealing BBB and regulating AQP4 expression, and suppressed apoptosis through extrinsic or intrinsic pathway. Plasmalemma permeability may be a potential target for TBI treatment.

• Authors: Hai-Jun Bao, Tao Wang, Ming-Yang Zhang, Ran Liu, Ding-Kun Dai, Yao-Qi Wang, Long Wang, Lu Zhang, Yu-Zhen Gao, Zheng-Hong Qin, Xi-Ping Chen, Lu-Yang Tao
• Journal: Neurochemical research (Neurochem Res) Vol. 37 Issue 12 Pg. 2856-67 (Dec 2012) ISSN: 1573-6903 [Electronic] United States
• PMID: 23011204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Poloxamer

Topics

• Animals
• Base Sequence
• Blood-Brain Barrier
• Blotting, Western
• Brain Edema (prevention & control)
• Brain Injuries (drug therapy, physiopathology)
• Cell Death (drug effects)
• DNA Primers
• Fluorescent Antibody Technique
• Male
• Maze Learning
• Mice
• Poloxamer (pharmacology, therapeutic use)
• Reverse Transcriptase Polymerase Chain Reaction