Lipocalin-2 deficiency attenuates neuroinflammation and brain injury after transient middle cerebral artery occlusion in mice.
Lipocalin-2 (LCN2) is a secreted protein of the lipocalin family, but little is known about the expression or the role of LCN2 in the central nervous system. Here, we investigated the role of LCN2 in ischemic stroke using a rodent model of transient cerebral ischemia. Lipocalin-2 expression was highly induced in the ischemic brain and peaked at 24 hours after reperfusion. After transient middle cerebral artery occlusion, LCN2 was predominantly expressed in astrocytes and endothelial cells, whereas its receptor (24p3R) was mainly detected in neurons, astrocytes, and endothelial cells. Brain infarct volumes, neurologic scores, blood-brain barrier (BBB) permeabilities, glial activation, and inflammatory mediator expression were significantly lower in LCN2-deficient mice than in wild-type animals. Lipocalin-2 deficiency also attenuated glial neurotoxicity in astrocyte/neuron cocultures after oxygen-glucose deprivation. Our results indicate LCN2 has a critical role in brain injury after ischemia/reperfusion, and that LCN2 may contribute to neuronal cell death in the ischemic brain by promoting neurotoxic glial activation, neuroinflammation, and BBB disruption.
1] Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea [2] Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Myungwon
M
Jin
1] Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea [2] Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Jong-Heon
JH
Kim
Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Eunha
E
Jang
Department of Physiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Young Mi
YM
Lee
1] Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea [2] Department of Physiology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Hyung
H
Soo Han
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Gyeongnam, Republic of Korea.
Dong Kyun
DK
Woo
Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Dong Ho
DH
Park
Department of Pharmacology, Chonnam National University Medical School, Gwangju, Republic of Korea.
Hyun
H
Kook
1] Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea [2] Department of Biomedical Sciences, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Kyoungho
K
Suk
D000209:Acute-Phase Proteins / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D003470:Culture Media; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000276:immunology*; D015513:Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D015427:Reperfusion Injury / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000209:Acute-Phase Proteins; D003470:Culture Media; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse