Therapeutic targeting of microglia mediated oxidative stress after neurotrauma.

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.

Spinal cord injury chronically depresses glucose uptake in the rodent model.

The pathophysiology following spinal cord injury (SCI) progresses from its lesion epicenter resulting in cellular and systemic changes acutely, sub-acutely and chronically. The symptoms of the SCI depend upon the severity of the injury and its location in the spinal cord. However, there is lack of studies that have longitudinally assessed acute through chronic in vivo changes following SCI. In this combinatorial study we fill this gap by evaluating acute to chronic effects of moderate SCI in rats. We have used fluorodeoxyglucose (FDG) imaging with positron emission tomography (PET) as a marker to assess glucose metabolism, motor function, and immunohistochemistry to examine changes following moderate SCI. Our results demonstrate decreased FDG uptake at the injury site chronically at days 28 and 90 post injury compared to baseline. This alteration in glucose uptake was not restricted to the lesion site, showing depressed FDG uptake in non-injured areas (cervical spinal cord and cerebellum). The alteration in glucose uptake was correlated with reductions in neuronal cell viability and increases in glial cell activation at 90 days at the lesion site, as well as chronic impairments in motor function. These data demonstrate the chronic effects of SCI on glucose metabolism both within the lesion and distally within the spinal cord and brain.