Montelukast reduces grey matter abnormalities and functional deficits in a mouse model of inflammation-induced encephalopathy of prematurity.
Montelukast reduces grey matter abnormalities and functional deficits in a mouse model of inflammation-induced encephalopathy of prematurity.
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DOI：
10.1186/s12974-022-02625-5
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发表时间：
2022-10-29
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
早产儿脑病（EoP）影响约30%的出生小于32周妊娠的婴儿，并与胎儿的炎症高度相关。在这里，我们评估了孟鲁司特的疗效，广泛用于治疗儿童哮喘的半胱氨酰白三烯受体拮抗剂，以改善外周和中枢炎症，以及随后的灰质神经病理学和行为缺陷的小鼠模型的EoP。雄性CD-1小鼠用腹膜内（i. p.）生理盐水或白细胞介素-1 β（IL-1β，40 μg/kg，5 μL/g体重）从出生后第1-5天（P）±伴随孟鲁司特（1-30 mg/kg）。损伤后继续盐水或孟鲁司特治疗5天。从给药后4 h至P10，对全身和中枢炎症以及短期神经病理学进行评估。从P36至54对第二组动物进行行为测试、MRI和神经病理学评估。发现孟鲁司特减轻外周和中枢炎症，减少脑中促炎分子（IL-1β、IL-6、TNF）的表达。炎症诱导皮质中小清蛋白阳性中间神经元密度降低，高剂量孟鲁司特使其正常化。最低有效剂量3 mg/kg能够改善该炎症损伤模型中的焦虑和空间学习缺陷，并且接受该剂量孟鲁司特的动物中不存在皮质平均扩散率的改变。因此，在早产后早期给予孟鲁司特可能会改善EoP的灰质发育和结局。在线版本包含补充材料，可通过10.1186/s12974-022-02625-5获得。
Encephalopathy of prematurity (EoP) affects approximately 30% of infants born < 32 weeks gestation and is highly associated with inflammation in the foetus. Here we evaluated the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist widely used to treat asthma in children, to ameliorate peripheral and central inflammation, and subsequent grey matter neuropathology and behaviour deficits in a mouse model of EoP. Male CD-1 mice were treated with intraperitoneal (i.p.) saline or interleukin-1beta (IL-1β, 40 μg/kg, 5 μL/g body weight) from postnatal day (P)1–5 ± concomitant montelukast (1–30 mg/kg). Saline or montelukast treatment was continued for a further 5 days post-injury. Assessment of systemic and central inflammation and short-term neuropathology was performed from 4 h following treatment through to P10. Behavioural testing, MRI and neuropathological assessments were made on a second cohort of animals from P36 to 54. Montelukast was found to attenuate both peripheral and central inflammation, reducing the expression of pro-inflammatory molecules (IL-1β, IL-6, TNF) in the brain. Inflammation induced a reduction in parvalbumin-positive interneuron density in the cortex, which was normalised with high-dose montelukast. The lowest effective dose, 3 mg/kg, was able to improve anxiety and spatial learning deficits in this model of inflammatory injury, and alterations in cortical mean diffusivity were not present in animals that received this dose of montelukast. Repurposed montelukast administered early after preterm birth may, therefore, improve grey matter development and outcome in EoP. The online version contains supplementary material available at 10.1186/s12974-022-02625-5.
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影响因子：
5.7
作者：
Batalle D;O'Muircheartaigh J;Makropoulos A;Kelly CJ;Dimitrova R;Hughes EJ;Hajnal JV;Zhang H;Alexander DC;Edwards AD;Counsell SJ
通讯作者：
Counsell SJ
影响因子：
11
作者：
Canetta S;Bolkan S;Padilla-Coreano N;Song LJ;Sahn R;Harrison NL;Gordon JA;Brown A;Kellendonk C
通讯作者：
Kellendonk C
影响因子：
5.3
作者：
Corser-Jensen CE;Goodell DJ;Freund RK;Serbedzija P;Murphy RC;Farias SE;Dell'Acqua ML;Frey LC;Serkova N;Heidenreich KA
通讯作者：
Heidenreich KA
影响因子：
2.9
作者：
Evans, JF
通讯作者：
Evans, JF
影响因子：
5.7
作者：
Batalle, Dafnis;Eixarch, Elisenda;Gratacos, Eduard
通讯作者：
Gratacos, Eduard