Reducing neuroinflammation and improving neurobehavioral functions: the protective roles of resveratrol for germinal matrix hemorrhage in neonatal rat model
10.3760/cma.j.issn.2096-2932.2022.04.012
- VernacularTitle:白藜芦醇抑制新生大鼠生发基质出血后神经炎症及保护神经功能的作用
- Author:
Shengpeng LIU
1
;
Xiaoli ZHANG
;
Jun PENG
;
Ling GAO
;
Haoran ZHANG
;
Jun LU
Author Information
1. 深圳市人民医院（暨南大学第二临床医学院，南方科技大学第一附属医院）儿内科，深圳 518020
- Keywords:
Rat;
Resveratrol;
Germinal matrix hemorrhage;
Neurobehavior;
Neuroinflammation
- From:Chinese Journal of Neonatology
2022;37(4):343-349
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the roles of resveratrol in reducing neuroinflammation and improving neurobehavioral functions after germinal matrix hemorrhage (GMH) in neonatal rat model.Methods:GMH model was established intraparenchymally injecting bacterial collagenase in 7-day-old SD rats. 108 rats were randomly assigned into 18 groups (6 in each group), including 4 sham groups, GMH (12 h, 24 h, 72 h, 7 d) groups, 3 GMH+vehicle (dimethylsulfoxide, DMSO) groups, 5 GMH+resveratrol (10 mg/kg, 100 mg/kg, 1 000 mg/kg) groups and 2 GMH+resveratrol+EX527 (SIRT1 inhibitor) groups. Negative geotaxis and righting reflex tests were used to evaluate the short-term neurobehavior. Water maze, foot fault and Rotor-Rod tests were used to assess the long-term neurobehavior. Immunofluorescence was used to quantify the IL-1β and MPO positive cells (inflammatory markers) in peri-hematoma area. Western blot was used to evaluate the expression of relevant proteins in the brain.Results:Endogenous sirtuin-1(SIRT1) decreased to the lowest level at 24 h and then increased gradually. Phosphorylated NF-κB increased at 12 h, peaked at 72 h and returned to normal level at 7 d after GMH. Compared with the control group and other doses groups, GMH treated with resveratrol (100 mg/kg) had higher short-term behavioral scores at 48 h and 72 h. Compared with the control group, the resveratrol (100 mg/kg) group also had higher scores in water maze, foot fault and Rotor-Rod tests 22 days later. Immunofluorescence showed less positive IL-1β and MPO cells around hematoma in GMH+resveratrol group than both GMH+vehicle group and GMH+resveratrol+EX527 group. Western blot indicated that IL-1, TNF-α and IL-6 expressions were decreased in GMH+resveratrol group and Ex527 could offset the effects of resveratrol.Conclusions:Resveratrol (optimal dose: 100 mg/kg) can improve the short-term and long-term neurobehavioral functions of neonatal GMH rats. It can reduce GMH cells with positive inflammatory markers around the hematoma, possibly via inhibition of the SIRT1/NF-κB pathway. Resveratrol may be promising for the treatment of GMH patients.
