ABSTRACT
The COVID-19 Health System Response Monitor presents findings from a systematic approach to collect and synthesise up-to-date information on Singapore’s policy response to the COVID-19 outbreak. This publication is part of the APO’s COVID-19 HSRM series which presents detailed information on country-specific responses to COVID-19, to facilitate easy comparisons of health systems and public health, and policy responses to COVID-19. It also aims to strengthen evidence on the global response to the pandemic and allow for easy comparison of activities at national and sub-national levels. The series is updated to reflect changes in the health systems and policies to the COVID-19 response.
Subject(s)
COVID-19 , JapanABSTRACT
Methamphetamine (METH)-induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. The aims of the present study conducted in the mouse brain repetitively treated with METH were to (1) examine the redox status using the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethylpiperidine-1-oxyl (MCP) and (2) non-invasively visualize the brain redox status with electron paramagnetic resonance (EPR) imaging. The rate of reduction of MCP was measured from a series of temporal EPR images of mouse heads, and this rate was used to construct a two-dimensional map of rate constants called a "redox map." The obtained redox map clearly illustrated the change in redox balance in the METH-treated mouse brain that is a known result of oxidative damage. Biochemical assays also showed that the level of thiobarbituric acid-reactive substance, an index of lipid peroxidation, was increased in mouse brains by METH. The enhanced reduction in MCP observed in mouse brains was remarkably suppressed by treatment with the dopamine synthase inhibitor, α-methyl-p-tyrosine, suggesting that enhancement of the reduction reaction of MCP resulted from enzymatic reduction in the mitochondrial respiratory chain. Furthermore, magnetic resonance imaging (MRI) of METH-treated mice using a blood-brain barrier (BBB)-impermeable paramagnetic contrast agent revealed BBB dysfunction after treatment with METH for 7 days. MRI also indicated that the impaired BBB recovered after withdrawal of METH. EPR imaging and MRI are useful tools not only for following changes in the redox status and BBB dysfunction in mouse brains repeatedly administered METH, but also for tracing the drug effect after withdrawal of METH.