Lithium treatment mitigates white matter injury after intracerebral hemorrhage through brain-derived neurotrophic factor signaling in mice

Abstract

Intracerebral hemorrhage (ICH), a subtype of stroke with high morbidity and mortality, occurs mainly in the basal ganglia and causes white matter injury (WMI), resulting in severe motor dysfunction and poor prognosis in patients. The preservation of the white matter around the hematoma is crucial for motor function recovery, but there is currently no effective treatment for WMI following ICH. Lithium has been widely used for the treatment of bipolar disorder for decades. Although the protective effects of lithium on neurodegenerative diseases and cerebral trauma have been studied in recent years, whether it can be used to alleviate WMI after ICH remains to be researched. The results of this study revealed that ICH caused significant functional and pathological abnormalities in mice. After LiCl was administered to mice with ICH, behavioural performance and electrophysiological functions were improved and ICH-induced white matter pathological injury, including myelin sheath and axonal degeneration, was ameliorated. Furthermore, LiCl treatment decreased the death of mature oligodendrocytes (OLGs) in ICH mice, which may have been attributed to the enhanced expression of brain-derived neurotrophic factor (BDNF) regulated by the LiCl-induced inhibition of glycogen synthase kinase-3β (GSK-3β). The decreased death of OLGs was closely associated with decreased destruction of the myelin sheath and alleviated degradation of the axons. In summary, this study suggests that the protective effect of lithium on WMI after ICH might be related to an increased level of BDNF and that LiCl treatment may be a potential therapeutic method to palliate WMI after ICH.