Αρχειοθήκη ιστολογίου

Τετάρτη 6 Σεπτεμβρίου 2017

Constitutive activity of 5-HT2c receptors is present following incomplete spinal cord injury but is not modified after chronic SSRI or baclofen treatment

Following spinal cord injury (SCI), reflexes become hyperexcitable, leading to debilitating muscle spasms and compromised motor function. Previous work has described adaptations in spinal systems that might underlie this hyperexcitability, including an increase in constitutively active 5-HT2C receptors in spinal motoneurons. That work, however, examined adaptations following complete transection SCI, whereas SCI in humans is usually anatomically and functionally incomplete. We therefore evaluated whether constitutive activity of 5-HT2C receptors contributes to reflex hyperexcitability in an incomplete compression model of SCI and to spasms in vitro and in vivo. Our results confirm that 5-HT2C receptor constitutive activity contributes to reflex excitability following incomplete SCI. We also evaluated whether constitutive activity could be altered by manipulating neural activity levels following SCI, testing the hypothesis that it reflects homeostatic processes acting to maintain spinal excitability. We decreased neural activity following SCI by administering baclofen and increased activity by administering the SSRI fluoxetine. We found that drug administration produced minimal alterations in in vivo locomotor function or reflex excitability. Similarly, we found that neither baclofen nor fluoxetine altered the contribution of constitutively active 5-HT2C receptors to reflexes following SCI, although the contribution of 5-HT2C receptors to reflex activity was altered following SSRIs. These results confirm the importance of constitutively activity in 5-HT2C receptors to spinal hyperexcitability following SCI in the clinically relevant case of incomplete SCI, but suggest that this activity is not driven by homeostatic processes that act to maintain overall levels of spinal excitability.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2xQm3zh

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