Kim, Jae-Hong Kang, Ri Jin Hyeon, Seung Jae Ryu, Hoon Joo, Hyejin Bu, Youngmin Kim, Jong-Heon Suk, Kyoungho 2024-01-19T10:00:41Z 2024-01-19T10:00:41Z 2023-01-03 2023-04 1933-7213 https://pubs.kist.re.kr/handle/201004/113891 Reactive glial cells are hallmarks of brain injury. However, whether these cells contribute to secondary inflammatory pathology and neurological deficits remains poorly understood. Lipocalin-2 (LCN2) has inflammatory and neurotoxic effects in various disease models; however, its pathogenic role in traumatic brain injury remains unknown. The aim of the present study was to investigate the expression of LCN2 and its role in neuroinflammation following brain injury. LCN2 expression was high in the mouse brain after controlled cortical impact (CCI) and photothrombotic stroke (PTS) injury. Brain levels of LCN2 mRNA and protein were also significantly higher in patients with chronic traumatic encephalopathy (CTE) than in normal subjects. RT-PCR and immunofluorescence analyses revealed that astrocytes were the major cellular source of LCN2 in the injured brain. Lcn2 deficiency or intracisternal injection of an LCN2 neutralizing antibody reduced CCI- and PTS-induced brain lesions, behavioral deficits, and neuroinflammation. Mechanistically, in cultured glial cells, recombinant LCN2 protein enhanced scratch injury-induced proinflammatory cytokine gene expression and inhibited Gdnf gene expression, whereas Lcn2 deficiency exerted opposite effects. Together, our results from CTE patients, rodent brain injury models, and cultured glial cells suggest that LCN2 mediates secondary damage response to traumatic and ischemic brain injury by promoting neuroinflammation and suppressing the expression of neurotropic factors. English Elsevier BV Lipocalin-2 Is a Key Regulator of Neuroinflammation in Secondary Traumatic and Ischemic Brain Injury Article 10.1007/s13311-022-01333-5 1 Neurotherapeutics, v.30, no.3, pp.803 - 821 Neurotherapeutics 30 3 803 821 N scie scopus 000898473300001 2-s2.0-85143701316 Clinical Neurology Neurosciences Pharmacology & Pharmacy Neurosciences & Neurology Pharmacology & Pharmacy Article GELATINASE-ASSOCIATED LIPOCALIN NEUROTROPHIC FACTOR UP-REGULATION PSYCHIATRIC-DISORDERS DOPAMINERGIC-NEURONS PERIPHERAL-NERVE UNITED-STATES MICROGLIA ACTIVATION GDNF Astrocyte Microglia Neuroinflammation Lipocalin-2 Traumatic brain injury