Table 1.

Summary of studies on the potential benefits of P188.

Refs.	Study Design and Model	Testing Dose	Administration Route	Pharmacological Actions	Summary of Findings
[14]	• In vitro      embryonic day 14 rat fetal ventral mesencephalic cells • In vivo     25 female Wistar rats with hemiparkinsonism	• In vitro     200 µM • In vivo     Treatment group: 400000 embryonic day 14 rat ventral mesencephalic cells (single-cell suspension in the presence of P188, 200 µM) Control group: 400 000 cells that were not exposed to P188	• In vitro     N/A • In vivo    Intrastriatal injections/ transplantation for in vivo studies	P188 protects fetal dopaminergic cells by increasing cell survival and enhances striatal reinnervation and dopaminergic fiber outgrowth into the transplanted striatum in parkinsonian rats	P188 can be an essential adjunct to improve the clinical efficacy of neural transplantation for Parkinson’s disease
[15]	• In vitro      Human neuroblastoma (SH-SY5Y) cells • In vivo     4 groups x 16 mice in each group, adult male C57BL/6 mice (n = 64)	• In vitro      Pre-treatment with P188 10−6-10−3M for 1 h before 1-methyl-4-phenylpyridinium (MPP+, 100 μM treatment) • In vivo     P188 (0.4 g/kg or 0.8 g/kg) 30 min after MPTP administration in the first 5 days and twice a week in the next 21 days	• In vitro     N/A • In vivo Injection via the tail vein	P188 rescued MPP+-induced lysosomal dysfunction and impaired autophagy flux in SH-SY5Y cells. Also, P188 restored lysosomal membrane integrity in sub-acute MPTP mouse model and MPP+-treated SH-SY5Y cells. P188 ameliorated α-synuclein accumulation and behavioural impairment in chronic MPTP mouse model	P188 offers neuroprotection against DA neuron damage and decreased protein level aggregation of α-synuclein. P188-mediated lysosomal membrane integrity restoration could be a therapeutic intervention for PD and related neurodegenerative diseases
[16]	• In vivo Mature male CD1 mice (n = 424)	• In vivo P188 (2, 4, 8, 16 mg/ml, dissolved in normal saline) was given 30 min before TBI.	• In vivo Intravenous tail injection	P188 pre-treatment attenuates TBI-induced brain edema by restoring and resealing BBB integrity, regulating AQP4 expression, and suppressing TBI-induced neural cell death/ apoptosis through the extrinsic or intrinsic pathway, and improves neurological function	Poloxamer 188 could restore the intactness of the plasma membrane and play a cytoprotective action in plasmalemma permeability, which could be a potential target for TBI treatment
[17]	• In vitro     PC2 cells, a subline derived from rat pheochromocytoma cell line PC12	• In vitro       100 μM P188	• In vitro     N/A	P188 demonstrated acute membrane repair and restored cell viability at 24 h post-injury. The membrane resealing property of P188 offers protection by inhibiting apoptosis and preventing necrosis	The neuroprotection offered by P188 from both necrosis and apoptosis allows it to be a potential treatment in acute membrane damage due to trauma, which leads to upstream of the many signaling cascades, ultimately contributing to subsequent pathology
[18]	• In vitro     Mouse brain endothelial cell	• In vitro       P188, 0.5 mM	• In vitro     N/A	P188 was demonstrated to reconstitute the BBB membrane and down-regulated the secretion of matrix metalloproteinases (MMP). P188 mitigates the BBE disruption by alleviating the loss of tight junctions	Treatment of brain endothelial cells with P188 could serve as a potential treatment in response to traumatic brain injury by repairing the damaged brain endothelium
[19]	• In vivo     Adult male Wistar rats (n = 23)	• In vivo       Vepoloxamer, (purified P188), 300 mg/kg, for over 60 minutes starting at 2 hours post-injury	• In vivo     Intravenous infusion into tail veins	Initiation of Vepoloxamer treatment 2 h post-injury significantly improved functional sensorimotor recovery and spatial learning, reduced cortical lesion volume by 20%, and decreased activation of microglia/macrophages and astrogliosis in brain regions such as the injured cortex, corpus callosum, and hippocampus. Vepoloxamer treatment reduced brain and microthrombosis formation	Vepoloxamer treatment provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcomes. Further research is needed to explore the optimal dose and the mechanisms underlying the beneficial effects of vepoloxamer treatment for TBI
[20]	• In vitro     Human neuroblastoma (SH-SY5Y) cells	• In vitro      2 μg P188 (final concentration of 20 ng/μl)	• In vitro      N/A	P188 promotes cell survival/ viability of oligomer-treated cells in a time-dependent manner. P188 reduces bidirectional leakage of molecules across the damaged membrane from exposure to various kinds of amyloid oligomers	P188 could potentially act as a therapeutic against neuronal membrane damage by temporarily repairing membrane defects and reinforcing the cell membrane permeabilization caused by oligomers
[21]	• In vivo     Male B6SJL-Tg(SOD1*G93A)1Gur/J mice (n = 26)	• In vivo        Purified P188,10mM	• In vivo      Artificial cerebrospinal fluid [aCSF]) via mini-osmotic pumps. The osmotic pump (delivering 0.15 μl/h) provided 1.5 pM/h of P188 solution or aCSF for 42 days	P188 treatment in G93ASOD1 transgenic mice ameliorates the pathology by significantly delaying the onset of symptoms, extended survival, and decreased motoneuron death	Using the P188 or a close analog, it targets the mtSOD1 misfolding-induced membrane toxicity, and this may provide a new direction for ALS treatment or may be effective in FALS patients bearing SOD1 mutations
[22]	• In vitro      Fetal hippocampal neurons	• In vitro        100 uM P188	• In vitro      N/A	P188 protects hippocampal and cerebellar neurons following severe excitotoxic and oxidative injury in vitro through membrane-targeted mechanisms, blocking lipid peroxidation and preventing the loss of intracellular contents	P188 demonstrated direct restoration of plasma membrane integrity following a physical disruption and strong, membrane-targeted neuroprotection. P188 could be an approach to the treatment of an acute neuronal injury
[23]	• In vivo      Female Sprague-Dawley rats (n = 30)	• In vivo        0.2 mM P188	• In vivo     Intravenous administration 1 hr after crush injury	Significant improvement in axonal conduction for animals treated with P188. The segment of the axon distal to the site of injury in the P188-treated group increased in nerve fiber density. Intravenous P188 demonstrated more rapid structural and functional nerve recovery	P188 may be a therapeutic approach to treate peripheral nerve injury
[24]	• In vitro      HT22 murine hippocampal cells • In vivo      Male ICR mice	• In vitro      P188 (10-4 M in PBS) • In vivo      Short-term outcome experiment      P188 (small, medium and large dosages were 0.2, 0.4, 0.8 g/kg body weight, respectively)      Longterm-outcome experiment      P188 (0.4 g/kg) 5 min before reperfusion, and thereafter, daily administration of P188 (0.4 g/kg) for three weeks post-ischemia/reperfusion	• In vitro     N/A • In vivo     Short-term outcome experiment     Injection via tail vein 5 min before perfusion     Long-term outcome experiment    Intraperitoneal injections	P188 treatment significantly reduced the PI-positive cells with ischemia/reperfusion injury and repaired the HT22 cell membrane rupture. It also significantly decreased infarct volume, ameliorated the brain edema and neurological symptoms 24 h after ischemia/reperfusion. In the long-term outcome study, P188 markedly alleviated brain atrophy and motor impairments and elevated survival rate in 3 weeks of the post-stroke period	P188 offers long-term protection against cerebral ischemia/reperfusion injury by preserving BBB impermeability, inhibiting MMP-9, and membrane resealing