Clobetasol Attenuates White Matter Injury by Promoting Oligodendrocyte Precursor Cell Differentiation

2020 ◽  
Vol 55 (4) ◽  
pp. 188-196
Author(s):  
Xuewen Su ◽  
Haifeng Yuan ◽  
Yuxin Bai ◽  
Junlong Chen ◽  
Mingze Sui ◽  
...  
Keyword(s):  
White Matter ◽  
Rat Model ◽  
Myelin Sheath ◽  
White Matter Injury ◽  
Neurological Deficits ◽  
Treatment Groups ◽  
Myelin Sheaths ◽  
Neurobehavioral Function ◽  
Sheath Formation ◽  
Oligodendrocyte Precursor

<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.

scholarly journals Activin A Improves White Matter Injury in Neonatal Rats via Noggin/bmp4/id2 Signaling

2021 ◽  
Author(s):  
Xiaojuan Su ◽  
Jun Tang ◽  
Lingyi Huang ◽  
Dongqiong Xiao ◽  
Xia Qiu ◽  
...  
Keyword(s):  
White Matter ◽  
Rat Model ◽  
Myelin Sheath ◽  
Immunofluorescence Staining ◽  
White Matter Injury ◽  
Morris Water Maze Test ◽  
Oligodendrocyte Progenitor Cells ◽  
Protective Effects ◽  
Neonatal Rats

Abstract BackgroundActivin A (Act A) has been revealed to enhance the differentiation of oligodendrocyte progenitor cells (OPCs) in vitro. Here we aim to elucidate its roles and mechanisms in a rat model of white matter injury (WMI). MethodsAct A was injected into the lateral ventricle of a hypoxia-ischemia induced WMI rat model. Hematoxylin & eosin staining was used to detect pathological changes. Immunofluorescence staining was used to assess OPC proliferation, migration, apoptosis, and differentiation. Myelin sheath and axon formation were detected via immunofluorescence staining, Western blotting, and electron microscopy. Behavioral assessment of rats was performed with the Morris water maze test. ResultsAct A attenuated the pathological damages, enhanced the formation of myelin sheath and myelinated axons and improved the behavior of WMI rats by promoting OPC proliferation and differentiation. However, Act A showed no significant effects on OPC migration or apoptosis. Interestingly, we found that Act A could enhance Noggin expression, which in turn inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the protective effects of Act A in WMI. ConclusionsAct A improves WMI in neonatal rats via Noggin/BMP4/Id2 signalling.

Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia

2013 ◽  
Vol 1495 ◽  
pp. 11-17 ◽  
Author(s):  
Yingzhu Chen ◽  
Qiong Yi ◽  
Gang Liu ◽  
Xue Shen ◽  
Lihui Xuan ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Ischemia ◽  
Myelin Sheath ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Whole Brain

Abstract WMP118: Involvement of MMP-9 in Inflammation-induced White Matter Injury in a Novel Rat Model of Vascular Cognitive Impairment

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Fakhreya Y Jalal ◽  
Jeffrey Thompson ◽  
Yi Yang ◽  
Gary A Rosenberg
Keyword(s):  
T Cells ◽  
Cognitive Impairment ◽  
White Matter ◽  
Rat Model ◽  
Hypoxia Inducible Factor ◽  
Treated Group ◽  
White Matter Injury ◽  
Image Size ◽  
Apparent Diffusion Coefficients ◽  
Long Term Treatment

Objective: We have recently developed a rat model of white matter (WM) injury in stroke-prone spontaneously hypertensive rats (SHR-SP), which shows chronic oligodendrocyte death, blood-brain barrier (BBB) disruption, and cognitive impairment. In this study, we investigated the mechanisms of white matter damage secondary to chronic hypertensive disease. Methods: At 12 weeks of age, we subjected SHR-SP to permanent unilateral carotid artery occlusion (UCAO) followed by the Japanese permissive diet (JPD) and 1 % NaCl in drinking water. One group of UCAO/JPD rats received minocycline (50 mg/kg in DMSO, i.p. every other day for 9 weeks) and another had only UCAO/JPD with DMSO. WM lesions were characterized histologically, biochemically, and by MRI; cognitive impairment was tested by Morris water maze. Results: One to 3 weeks after UCAO/JPD, we found an increase in hypoxia inducible factor-1α (HIF-1α) in astrocytes, a fall in pyrol hydroxylase-2 (PHD-2), and an increase in matrix metalloproteinase-9 (MMP-9) expression. At week 1, there was infiltration of T-cells and MMP-9 co-localized with endothelial cells and neutrophils. By 3 weeks, we observed IgG leakage, indicating disruption of the BBB, with scattered hemorrhages. Long term treatment with minocycline prevented cognitive impairment along with reduction in T2-weighted image size, apparent diffusion coefficients, and fractional anisotropy compared to the vehicle-treated group. Relative cerebral blood flow was unaffected by minocycline treatment. Conclusion: Our results suggest that hypoxic hypoperfusion of the deep WM, which occurs secondary to hypertensive damage to blood vessels, initiates expression of MMP-9 and migration of T-cells, disrupting the BBB and damaging WM. The anti-inflammatory agent, minocycline, significantly protected the deep WM from injury.

scholarly journals Diffusion Tensor Imaging Reveals White Matter Injury in a Rat Model of Repetitive Blast-Induced Traumatic Brain Injury

2014 ◽  
Vol 31 (10) ◽  
pp. 938-950 ◽  
Author(s):  
Evan Calabrese ◽  
Fu Du ◽  
Robert H. Garman ◽  
G. Allan Johnson ◽  
Cory Riccio ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Diffusion Tensor Imaging ◽  
Brain Injury ◽  
White Matter ◽  
Rat Model ◽  
Diffusion Tensor ◽  
White Matter Injury

scholarly journals White matter injury induced by diabetes in acute stroke is clinically relevant: A preliminary study

2016 ◽  
Vol 14 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Xinfeng Yu ◽  
Ruirui Song ◽  
Yerfan Jiaerken ◽  
Lixia Yuan ◽  
Peiyu Huang ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Corticospinal Tract ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Neurological Deficits ◽  
Diabetic Patients ◽  
Stroke Severity ◽  
Superior Longitudinal Fasciculus ◽  
Poor Outcome

The importance of white matter injury induced by diabetes in stroke severity and prognosis is largely unknown. We aimed to investigate the relationship between diabetes-related white matter injury beyond stroke lesions with acute neurological deficits and clinical outcome after stroke. In total, 36 stroke patients within 3–7 days after onset were enrolled. Neurological deficits on admission were assessed by National Institute of Health Stroke Score, and poor outcome at 3 months was defined as modified Rankin score >2. White matter tracts were compared between patients with diabetic and non-diabetic stroke using fractional anisotropy from diffusion tensor imaging. Regional white matter abnormality with decreased fractional anisotropy was observed in diabetic patients ( n = 18) when compared to non-diabetic patients ( n = 18). Decreased fractional anisotropy in ipsilesional distal corticospinal tract was independently associated with higher National Institute of Health Stroke Score motor component score ( β = −0.444, p = 0.005), and decreased fractional anisotropy in contralesional superior longitudinal fasciculus I was independently related to poor outcome (odds ratio, 0.900; p = 0.033). Our findings suggested that only white matter injury induced by diabetes in specific tracts like corticospinal tract and superior longitudinal fasciculus beyond stroke lesions has clinically relevant, providing insight into the mechanism of stroke recovery under the diabetic condition.

Protective effects of pentoxifylline on lipopolysaccharide-induced white matter injury in a rat model of periventricular leukomalasia

2013 ◽  
Vol 26 (18) ◽  
pp. 1865-1871 ◽  
Author(s):  
Mustafa Dilek ◽  
Abdullah Kumral ◽  
Emre Okyay ◽  
Seda Ozbal ◽  
Kazim Tugyan ◽  
...  
Keyword(s):  
White Matter ◽  
Rat Model ◽  
White Matter Injury ◽  
Protective Effects

scholarly journals Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

2015 ◽  
Vol 36 (1) ◽  
pp. 187-198 ◽  
Author(s):  
Akihiro Shindo ◽  
Anna C Liang ◽  
Takakuni Maki ◽  
Nobukazu Miyamoto ◽  
Hidekazu Tomimoto ◽  
...  
Keyword(s):  
White Matter ◽  
Cerebral Ischemia ◽  
Nerve Conduction ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Subcortical White Matter ◽  
Experimental Models ◽  
White Matter Injury ◽  
Cerebral White Matter ◽  
Myelin Sheaths

Oligodendrocytes are one of the major cell types in cerebral white matter. Under normal conditions, they form myelin sheaths that encircle axons to support fast nerve conduction. Under conditions of cerebral ischemia, oligodendrocytes tend to die, resulting in white-matter dysfunction. Repair of white matter involves the ability of oligodendrocyte precursors to proliferate and mature. However, replacement of lost oligodendrocytes may not be the only mechanism for white-matter recovery. Emerging data now suggest that coordinated signaling between neural, glial, and vascular cells in the entire neurovascular unit may be required. In this mini-review, we discuss how oligodendrocyte lineage cells participate in signaling and crosstalk with other cell types to underlie function and recovery in various experimental models of subcortical white-matter injury.

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