Protective Effects of Estrogen via Nanoparticle Delivery to Attenuate Myelin Loss and Neuronal Death after Spinal Cord Injury.

Spinal cord injury (SCI) is associated with devastating neurological deficits affecting more than 11,000 Americans each year. Although several therapeutic agents have been proposed and tested, no FDA-approved pharmacotherapy is available for SCI treatment. We have recently demonstrated that estrogen (E2) acts as an antioxidant and anti-inflammatory agent, attenuating gliosis in SCI. We have also demonstrated that nanoparticle-mediated focal delivery of E2 to the injured spinal cord decreases lesion size, reactive gliosis, and glial scar formation. The current study tested in vitro effects of E2 on reactive oxygen species (ROS) and calpain activity in microglia, astroglia, macrophages, and fibroblasts, which are believed to participate in the inflammatory events and glial scar formation after SCI. E2 treatment decreased ROS production and calpain activity in these glial cells, macrophages, and fibroblast cells in vitro. This study also tested the efficacy of fast- and slow-release nanoparticle-E2 constructs in a rat model of SCI. Focal delivery of E2 via nanoparticles increased tissue distribution of E2 over time, attenuated cell death, and improved myelin preservation in injured spinal cord. Specifically, the fast-release nanoparticle-E2 construct reduced the Bax/Bcl-2 ratio in injured spinal cord tissues, and the slow-release nanoparticle-E2 construct prevented gliosis and penumbral demyelination distal to the lesion site. These data suggest this novel E2 delivery strategy to the lesion site may decrease inflammation and improve functional outcomes following SCI.

Thirst as an ingestive behavior: A brief review on physiology and assessment.

BACKGROUND: Thirst is a sensation normally aroused by a lack of water and associated with a desire to drink more fluid. AIM: The aims of this brief review are twofold: (a) to summarize the thirst mechanism in how it is initiated and diminished, and (b) to describe techniques to assess human thirst accurately in a variety of situations. DISCUSSION: Thirst is maintained via a feedback-controlled mechanism, regulated by central and peripheral factors, as well as social and psychological cues. Most studies of thirst have focused on the initiation of water intake and the neural mechanisms responsible for this vital behavior. Less attention has been paid to the stimuli and mechanisms that terminate a bout of drinking and limit fluid ingestion, such as oropharyngeal and gastric signals, coupled with osmotic sensations. Thirst perception is typically assessed by subjective ratings using a variety of questionnaires, rankings, or visual analog scales. However, the appropriate perceptual tool may not always be used for the correct assessment of thirst perception. CONCLUSIONS: In considering the many factors involved in thirst arousal and inhibition, similar questions need to be considered for the correct assessment of this ingestive behavior.