Chun, Heejung Lim, Jiwoon Park, Ki Duk Lee, C. Justin 2024-01-19T13:00:30Z 2024-01-19T13:00:30Z 2022-01-25 2022-02 0894-1491 https://pubs.kist.re.kr/handle/201004/115778 Reactive astrocytes manifest molecular, structural, and functional alterations under various pathological conditions. We have previously demonstrated that the reactive astrocytes of the stab wound injury model (STAB) display aberrant cellular gamma-aminobutyric acid (GABA) content and tonic GABA release, whereas the active astrocytes under enriched environment (EE) express high levels of proBDNF. However, the role of monoamine oxidase B (MAO-B) in reactive astrogliosis and hypertrophy still remains unknown. Here, we investigate the role of MAO-B, a GABA-producing enzyme, in reactive astrogliosis in STAB. We observed that the genetic removal of MAO-B significantly reduced the hypertrophy, scar formation, and GABA production of reactive astrocytes, whereas the MAO-B overexpression under glial fibrillary acidic protein (GFAP) promoter enhanced the levels of GFAP and GABA. Furthermore, we found that one of the by-products of the MAO-B action, H2O2, but not GABA, was sufficient and necessary for the hypertrophy of reactive astrocytes. Notably, we identified two potent pharmacological tools to attenuate scar-forming astrogliosis-the recently developed reversible MAO-B inhibitor, KDS2010, and an H2O2 scavenger, crisdesalazine (AAD-2004). Our results implicate that inhibiting MAO-B activity has dual beneficial effects in preventing astrogliosis and scar-formation under brain injury, and that the MAO-B/H2O2 pathway can be a useful therapeutic target with a high clinical potential. English John Wiley & Sons Inc. Inhibition of monoamine oxidase B prevents reactive astrogliosis and scar formation in stab wound injury model Article 10.1002/glia.24110 1 GLIA, v.70, no.2, pp.354 - 367 GLIA 70 2 354 367 N scie scopus 000712409900001 2-s2.0-85118227145 Neurosciences Neurosciences & Neurology Article ASTROCYTES GABA PTEN brain injury glial scar H2O2 MAO-B reactive astrocytes