Clobetasol Attenuates White Matter Injury by Promoting Oligodendrocyte Precursor Cell Differentiation

Abstract

<b><i>Introduction:</i></b> White matter injury (WMI) is the most common brain injury in preterm infants and can result in life-long neurological deficits. The main cause of WMI is damage to the oligodendrocyte precursor cells (OPC) in the brain that results in delayed myelin sheath formation, or the destruction of existing myelin sheaths. OPC undergo highly regulated and strictly timed developmental changes that result in their transformation to mature oligodendrocytes capable of myelin production. <b><i>Objective:</i></b> Studies have shown that clobetasol strongly promotes differentiation of OPC into myelin sheaths. Therefore, we hypothesized that clobetasol may be a therapeutic option for the treatment of preterm WMI. <b><i>Methods:</i></b> We induced a WMI rat model and observed white matter damage under an optical microscope. Rats subjected to WMI were injected intraperitoneally with clobetasol (2 or 5 mg/kg daily) from day 1 to day 5 in the early treatment groups, or from day 6 to day 10 in the late treatment groups. After 17 days, the rats were sacrificed and the expression of myelin basic protein (MBP) was visualized using immunofluorescence. In addition, we evaluated myelin sheath formation using electron microscopy. The rats were also subjected to the suspension test, ramp test, and open field test to evaluate neurobehavioral functions. <b><i>Results:</i></b> A rat model of WMI was successfully induced. It was found that clobetasol significantly induced MBP expression and myelin sheath formation and improved neurobehavioral function in the rats subjected to WMI. <b><i>Conclusions:</i></b> Our results indicate that clobetasol attenuates WMI by promoting OPC differentiation, and it may be an effective therapeutic agent for the treatment of preterm WMI.

Nursing Education of Lateral Oblique Complications of Neurosurgery under Microscope

“…The main control computer as a human-computer interaction interface and user input control signal platform, care bed motor control drive system to complete the analysis of control signal, and drive the corresponding control bed parts of the motor [ 18 , 19 ]. The nursing bed should meet the various necessary positions and postures which are conducive to the nursing person's rehabilitation and self-care.…”

Myelin sheath injury and repairment after subarachnoid hemorrhage

“…For example, ethyl pyruvate (EP) ( He et al, 2019 ; He et al, 2021 ), osteopontin ( Selvaraju et al, 2004 ), structural analog of BDNF(55), nanoparticles containing leukemia inhibitory factor ( Rittchen et al, 2015 ), clemastine ( Li et al, 2015 ), endothelin 2 (58), human hair keratin ( Xu et al, 2003 ), the cycloskeleton adapter protein anilin (ANLN) ( Erwig et al, 2019 ), DL-3-n-butylphthalide (NBP) ( Wu et al, 2019 ) and FMRP (62) can be used to treat this injury. The third aspect is to search for marketed drugs with therapeutic effects on myelin sheath injury, such as clobetasol ( Su et al, 2020 ), trifluoperazine ( Khaledi et al, 2021 ), sildenafil ( Nunes et al, 2016 ), adrenomedullin ( Maki et al, 2015 ), omega-3 polyunsaturated fatty acids ( Pu et al, 2013 ), ascorbic acid ( Nam et al, 2019 ), fluoxetine ( Li et al, 2020a ), melatonin ( Abo Taleb and Alghamdi, 2020 ) and a mixture containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin ( Hauser et al, 2020 ). The fourth facet is to investigate Chinese herbal medicine and its extract that can treat myelin sheath injury, such as Honokiol ( Tan et al, 2022a ), Astaxanthin ( Lotfi et al, 2021 ), Shenling oral liquid ( Liu et al, 2020b ; Zheng et al, 2021 ), Rosmarinic acid ( Li et al, 2020b ), Naringenin ( Rong et al, 2017 ), Salvianolic acid B (78), Tanshinone IIA (79), Bushen Yisui capsule ( Rabinovich and Kacen, 2012 ; Zhao et al, 2018 ), the herbal medicine Ninjin ‘yoeito ( Seiwa et al, 2007 ) and Quercetin ( Naeimi et al, 2018 ; Tan et al, 2022b ), among other medicines.…”

Oligodendrocyte Development and Implication in Perinatal White Matter Injury

“…Administration of FTY720 in neonatal model of oxygen-toxicity is reported to attenuate hyperoxia-induced hypomyelination through reduction of hyperoxia-induced oxidative stress and inflammation accompanied with direct protection of developing OLs (Serdar et al, 2016). Several other drugs and biological compounds, such as Pioglitazone (PPAR-γ agonist) (Yeh et al, 2021), Clemastine (M1 muscarinic acetylcholine receptor antagonist) (Cree et al, 2018), miconazole (ERK 1/2 activator) (Su et al, 2018), clobetasol (Smoothened receptor agonist) (Su et al, 2020) and IDR-1018 (synthetic immunomodulator) (Bolouri et al, 2014) have been identified by HTS to have myelin enhancing property in preclinical and/or clinical trials, although their potential in treating prenatal WMI has not been explored.…”

“…Several other drugs and biological compounds, such as Pioglitazone (PPAR-γ agonist) ( Yeh et al, 2021 ), Clemastine (M1 muscarinic acetylcholine receptor antagonist) ( Cree et al, 2018 ), miconazole (ERK 1/2 activator) ( Su et al, 2018 ), clobetasol (Smoothened receptor agonist) ( Su et al, 2020 ) and IDR-1018 (synthetic immunomodulator) ( Bolouri et al, 2014 ) have been identified by HTS to have myelin enhancing property in preclinical and/or clinical trials, although their potential in treating prenatal WMI has not been explored.…”