Propofol Limits Microglial Activation after Experimental Brain Trauma through Inhibition of Nicotinamide Adenine Dinucleotide Phosphate Oxidase

Abstract

The neuroprotective effects of propofol after TBI appear to be mediated, in part, through the inhibition of NADPH oxidase.

Repeated Mild Traumatic Brain Injury Causes Chronic Neuroinflammation, Changes in Hippocampal Synaptic Plasticity, and Associated Cognitive Deficits

“…We next used the object exploration and discrimination trials of NOR task to assess recognition memory function 13,18,22 and found that repeated mTBI resulted in significant cognitive impairments when compared with sham rats (Po0.01) and single mTBI rats (Po0.05, Figure 3D). Rats with a single mTBI had a significantly impaired discrimination index compared with sham rats (Po0.05).…”

“…The estimated number of surviving neurons in each field was divided by the volume of the region of interest to obtain the cellular density expressed in counts/mm 3 . For stereological assessment of microglial activation, sections were stained and processed as described previously; 13,18 briefly, 60-mm sections were stained with Iba-1 (1:1,000; #019-19741 Wako Chemicals, Richmond, VA, USA) overnight, incubated with biotinylated anti-rabbit immunoglobulin G antibody (Vector Laboratories, Burlingame, CA, USA) for 2 hours. Sections processed with avidin-biotin-horseradish peroxidase for 1 hour (Vectastain elite ABC kit, Vector Laboratories), and then reacted with 3,30-diaminobenzidine (Vector Laboratories) for color development.…”

“…The apparatus is a rectangular open field (60 Â 24 Â 46 cm) with two adjacent circular zones, as previously described. 13,18 Zones were designated as 'familiar object' and 'novel object' zones using Any-Maze video tracking system. On PID 20, all animals were placed in the apparatus for 5 minutes each without objects present for habituation.…”

“…Stereoinvestigator software was used to count and classify the number of microglia in each of the three microglial morphologic phenotypes (ramified, hypertrophic, and bushy) at PID 28 days using the optical fractionator method of unbiased stereology as previously described. 13,18 Sections were analyzed using a Leica DM4000B microscope with an optical dissector size of 50 mm by 50 mm in the x and y-axis, respectively and a dissector height of 10 mm and guard-zone height of 4 mm from the top of the section. Microglial phenotypic classification was based on the length and thickness of the projections, the number of branches and the size of the cell body as previously described.…”

Preclinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

“…A comprehensive literature search provides a spectrum of contradicting outcomes in the context of motor function relative to cortical injury in the rat LFP model. Selected LFP studies have shown a correlation between a reduction in cortical lesion volume and motor function improvement (Luo et al, 2013;Otani et al, 2007). In contrast, other studies have shown improved motor behavior with no decrease in cortical lesion volume (Lippert-Gruener et al, 2007).…”