AD-16 Protects Against Hypoxic-Ischemic Brain Injury by Inhibiting Neuroinflammation.
10.1007/s12264-021-00816-3
- Author:
Zhihua HUANG
1
;
Zhengwei LUO
1
;
Andrea OVCJAK
1
;
Jiangfan WAN
1
;
Nai-Hong CHEN
2
;
Wenhui HU
3
;
Hong-Shuo SUN
4
;
Zhong-Ping FENG
5
Author Information
1. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
3. Key Laboratory of Molecular Target and Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, Guangdong, China.
4. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada. hss.sun@utoronto.ca.
5. Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada. zp.feng@utoronto.ca.
- Publication Type:Journal Article
- Keywords:
AD-16;
Neonatal hypoxic-ischemic brain injury;
Neuroinflammation;
Neuroprotection
- MeSH:
Animals;
Animals, Newborn;
Astrocytes/pathology*;
Brain/pathology*;
Brain Injuries/pathology*;
Glucose;
Hypoxia;
Hypoxia-Ischemia, Brain/drug therapy*;
Mice;
Neuroinflammatory Diseases;
Neuroprotective Agents/therapeutic use*;
Oxygen/therapeutic use*
- From:
Neuroscience Bulletin
2022;38(8):857-870
- CountryChina
- Language:English
-
Abstract:
Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic (HI) insult in the neonatal brain. AD-16 is a novel anti-inflammatory compound, recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators. In this study, we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation (OGD) in vitro and in mice with neonatal HI brain injury in vivo. We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury. Single dose post-treatment with AD-16 (1 mg/kg) improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 h. Chronic administration reduced the mortality rate and preserved whole-brain morphology following neonatal HI. The in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.
