Poloxamer-188 Can Attenuate Blood–Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model

Abstract

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.

Methamphetamine-mediated endoplasmic reticulum (ER) stress induces type-1 programmed cell death in astrocytes via ATF6, IRE1α and PERK pathways

“…We also observed reduction in MA-mediate apoptosis as a result of p65 silencing, which consolidates the role of NF-κB in MA-mediated toxicity. Since NF-κB activation leads to increase in pro-inflammatory cytokine/chemokines [15], cytotoxicity in brain microvascular endothelial cells via redox imbalance [79] and induce BBB dysfunction [80, 81], it is evident that it plays a multi-factorial role in MA-mediated cytotoxicity. The results presented in this study further supports the notion that MA employs several mechanisms that converge to NF-κB activation.…”

The effects of poloxamer 188 on the autophagy induced by traumatic brain injury

“…We investigated the effect of P188 in autophagy following TBI both in vitro and in vivo, in which autophagy was activated subsequent to P188 treatment. P188 can be directly embedded in the cell membrane lipid layer in vitro and restore plasma membrane integrity in multiple cells [8,16]. Recent studies have shown that autophagy is increased after TBI [4].…”

“…Traumatic brain injury (TBI) typically contributes to the disintegrity of cell membrane and threatens neuronal survival [9,18]. However, poloxamer 188 (P188) is an amphiphilic polyethylene-polypropylene-polyethylene copolymer, characterized by its properties in sealing membranes and restoring the plasma membrane integrity of neurons following membrane injury [8,13,16].…”

L-3-n-butylphthalide protect the neuro by reducing inflammation and brain edema in rat intracerebral hemorrhage model

“…The rats were deeply anesthetized with 10% chloral hydrate (3-5 mL/kg intraperitoneally) and decapitated. The brain water content was measured using a drying method [10]. With the cerebellar tissue removed, the wet weight of the right and left hemispheres was measured.…”