Poloxamer-188 can attenuate blood-brain barrier damage to exert neuroprotective effect in mice intracerebral hemorrhage model.
Blood-brain barrier (BBB) disruption and brain edema formation play important roles in the secondary neuronal death and neurological dysfunction induced by intracerebral hemorrhage (ICH). Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to be capable of sealing damaged cell membranes and decrease neuronal cell death. In this study, we explored whether P188 had a protective effect against ICH and its underlying mechanisms. Male ICR mice were subjected to infusion of type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. The results showed that P188-12 mg post-treatment by tail intravenous injection significantly ameliorated the neurological symptoms and brain edema, attenuated BBB permeability, and decreased cell insults and injury volume at 24 and 72 h after ICH. Furthermore, P188 maintained the protein levels of tight junction (TJ) proteins including claudin-5, occludin, and zonula occludens-1, and reversed the increases of nuclear factor-kappaB (NF-κB), matrix metalloproteinase (MMP)-2, and MMP-9 protein expression at 72 h post ICH. Immunofluorescence showed P188 treatment rearranged the structure of TJ proteins in a continuous and linear pattern. Therefore, the present study concludes that P188 can protect against ICH, and the protective effect was associated with preventing BBB disruption through NF-κB-MMPs-mediated TJ proteins degradation.
Department of Forensic Pathology, Institute of Forensic Sciences, Ministry of Justice, 200063, Shanghai, People's Republic of China.|Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Tao
T
Wang
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Xiping
X
Chen
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Zufeng
Z
Wang
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.|Department of Forensic Science, Medical School of Nantong University, 226001, Nantong, China.
Mingyang
M
Zhang
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Huanhuan
H
Meng
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Yuan
Y
Gao
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China.
Bin
B
Luo
Department of Forensic Science, Medical School of Soochow University, 215123, Suzhou, China. luyang.tao@163.com.
Luyang
L
Tao
Department of Forensic Pathology, Institute of Forensic Sciences, Ministry of Justice, 200063, Shanghai, People's Republic of China. yijiuchen@gmail.com.
Yijiu
Y
Chen
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020442:Poloxamer / Q000494:pharmacology* / Q000627:therapeutic use; D013501:Surface-Active Agents / Q000494:pharmacology* / Q000627:therapeutic use; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D018696:Neuroprotective Agents; D013501:Surface-Active Agents; D062725:Tight Junction Proteins; D020442:Poloxamer; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse