Issue release date: 12.11.2024
2Dalian Medical University, Dalian, Liaoning, China
3Third Military Medical University (Army Medical University), Southwest Hospital, Department of Neurosurgery, Chongqing, China DOI : 10.5137/1019-5149.JTN.27986-19.3 AIM: To determine whether melatonin (MLT) mitigates white matter (WM) injury by attenuating NOD-like receptor family pyrin domain-containing 3 (NLRP3)-associated oligodendrocyte apoptosis after subarachnoid hemorrhage (SAH).
MATERIAL and METHODS: SAH model C57BL/6J mice were created using an endovascular perforation technique. The mice were injected intraperitoneally with MLT at doses of 50 mg/kg, 150 mg/kg and 300 mg/kg. The animals were evaluated for neurological outcomes according to neurological score, brain water content, myelin degradation, amyloid precursor protein (APP) accumulation, apoptosis, and levels of NLRP3, caspase-1, interleukin-1?, Bcl-2, and Bcl-2-interacting mediator of cell death (Bim) expression after SAH.
RESULTS: MLT at a dose of 50 mg/kg improved neurological score, alleviated brain edema, and reduced WM injury. In addition, loss of myelin basic protein (MBP) and accumulation of APP, and expression in the ipsilateral/left hemisphere were found after SAH, and were reversed by MLT treatment. NLRP3 signal activation was found in microglia and apoptosis in oligodendrocytes were observed after SAH. MLT reduced oligodendrocyte apoptosis by regulating Bim and Bcl-2.
CONCLUSION: Results of this study indicated that MLT exerts a WM-protective effect in SAH pathophysiology, possibly by attenuating apoptosis in oligodendrocytes.
Keywords : Subarachnoid hemorrhage, White matter, Oligodendrocyte, Melatonin, Apoptosis, Mice