Experimental neurology
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Experimental neurology · Oct 2019
Enhanced descending pain facilitation in acute traumatic brain injury.
Acute and persistent pain are recognized consequences of TBI that can enhance suffering and significantly impair rehabilitative efforts. Both experimental models and clinical studies suggest that TBI may result in an imbalance between descending pain facilitatory and inhibitory pathways. The aim of this study was to assess the role of enhanced descending serotonin-mediated pain facilitation in a rat TBI model using selective spinal serotonergic fiber depletion with 5, 7-dihydroxytryptamine (DHT). ⋯ Additional immunohistochemical analyses of the lumbar spinal cord at 7 DPI revealed a robust bilateral microglial response in the superficial dorsal horns that was significantly reduced with DHT treatment. Furthermore, serotonin depletion also prevented the TBI-induced bilateral increase in c-Fos positive cells within the Rexed laminae I and II of the dorsal horns. These results indicate that in the weeks following TBI, pain may be responsive to 5-HT3 receptor antagonists or other measures which rebalance descending pain modulation.
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Experimental neurology · Oct 2019
Depression-like behavior corresponds with cardiac changes in a rodent model of spinal cord injury.
In previous studies we have shown that approximately 1/3 of male Sprague Dawley rats develop symptoms of depression following a spinal cord injury (SCI). Using established behavioral tests to measure depression in rodents, we found that after SCI, subjects characterized as depressed had decreased sucrose preference, open field activity, social exploration, and burrowing behavior. As some of these tests of depression could be affected by the compromised motor function inherent to the SCI condition, the current study examined whether non-subjective, physiological differences in heart rate and heart rate variability were also associated with depression, as seen in humans. ⋯ There was no difference between not-depressed SCI and intact rats on this measure. Therefore, in addition to behavior, depressed and not-depressed rats differ on measures of physiological function that are associated with depression in humans. These physiological differences further validate the rodent model of depression after SCI.
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Experimental neurology · Oct 2019
ReviewDocosahexaenoic acid decreased neuroinflammation in rat pups after controlled cortical impact.
Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children, yet specific therapies to treat TBI are lacking. Therapies that decrease the inflammatory response and enhance a reparative immune action may decrease oxidative damage and improve outcomes after TBI. Docosahexaenoic acid (DHA) modulates the immune response to injury in many organs. ⋯ Little is known about DHA effects on neuroinflammation in the developing brain. Further, it is not known if DHA given after developmental TBI exerts neuroprotective effects. We hypothesized that acute DHA treatment would decrease oxidative stress and improve cognitive outcome, associated with decreased pro-inflammatory activation of microglia, the brain's resident macrophages.
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Experimental neurology · Oct 2019
The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal.
Various antitumor drugs, including paclitaxel, frequently cause chemotherapy-induced peripheral neuropathy (CIPN) that can be sustained even after therapy has been completed. The current work was designed to evaluate R-47, an α7 nAChR silent agonist, in our mouse model of CIPN. R-47 was administered to male C57BL/6J mice prior to and during paclitaxel treatment. ⋯ Moreover, R-47 does not increase NSCLC cell viability, colony formation, or proliferation, and does not interfere with paclitaxel-induced growth arrest, DNA fragmentation, or apoptosis. Most importantly, R-47 does not increase the growth of A549 tumors or interfere with the antitumor activity of paclitaxel in tumor-bearing mice. These studies suggest that R-47 could be a viable and efficacious approach for the prevention and treatment of CIPN that would not interfere with the antitumor activity of paclitaxel or promote lung tumor growth.