Therapeutic targeting of microglia mediated oxidative stress after neurotrauma

Abstract

Inflammation is a primary component of the central nervous system injury response. Traumatic brain and spinal cord injury are characterized by a pronounced microglial response to damage, including alterations in microglial morphology and increased production of reactive oxygen species (ROS). The acute activity of microglia may be beneficial to recovery, but continued inflammation and ROS production is deleterious to the health and function of other cells. Microglial nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), mitochondria, and changes in iron levels are three of the most common sources of ROS. All three play a significant role in post-traumatic brain and spinal cord injury ROS production and the resultant oxidative stress. This review will evaluate the current state of therapeutics used to target these avenues of microglia-mediated oxidative stress after injury and suggest avenues for future research.

Keywords: NADPH oxidase; iron; microglia; mitochondria; oxidative stress; spinal cord injury; traumatic brain injury.

FIGURE 1

Microglia mediated oxidative stress leads to neurotoxicity.

FIGURE 2

Oxidative stress in microglia. Microglia can produce reactive oxygen species (ROS) through NOX2, mitochondrial oxidative phosphorylation, and the Fenton reaction with iron. ROS act as signaling molecules to mediate pathways pivotal in microglial functions.

FIGURE 3

Reactive oxygen species in microglia. NOX2, the primary reactive oxygen species (ROS)-generating enzyme in microglia, produces superoxide. Superoxide dismutase then catalyzes the dismutation of superoxide to produce hydrogen peroxide. Iron reacts with hydrogen peroxide, generating hydroxyl radicals.