Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.

Spinal cord injury (SCI) induces a cascade of processes that may further expand the damage (secondary injury) or, alternatively, may be part of a safeguard response. Here we show that after a moderate-severe contusive SCI in rats there is a significant and very early increase in the spinal cord cont...

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Autores principales:	Angel Arevalo-Martin, Daniel Garcia-Ovejero, Yolanda Sierra-Palomares, Beatriz Paniagua-Torija, Ines Gonzalez-Gil, Silvia Ortega-Gutierrez, Eduardo Molina-Holgado
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/344bb135cc804e69a00299347a630684
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spelling	oai:doaj.org-article:344bb135cc804e69a00299347a6306842021-11-18T08:09:00ZEarly endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.1932-620310.1371/journal.pone.0049057https://doaj.org/article/344bb135cc804e69a00299347a6306842012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23152849/?tool=EBIhttps://doaj.org/toc/1932-6203Spinal cord injury (SCI) induces a cascade of processes that may further expand the damage (secondary injury) or, alternatively, may be part of a safeguard response. Here we show that after a moderate-severe contusive SCI in rats there is a significant and very early increase in the spinal cord content of the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA). Since 2-AG and AEA act through CB1 and CB2 cannabinoid receptors, we administered at 20 minutes after lesion a single injection of their respective antagonists AM281 and AM630 alone or in combination to block the effects of this early endocannabinoid accumulation. We observed that AM281, AM630 or AM281 plus AM630 administration impairs the spontaneous motor recovery of rats according to the Basso-Beattie-Bresnahan (BBB) locomotor scale. However, blockade of CB1, CB2 or both receptors produced different effects at the histopathological level. Thus, AM630 administration results at 90 days after lesion in increased MHC-II expression by spinal cord microglia/monocytes and reduced number of serotoninergic fibres in lumbar spinal cord (below the lesion). AM281 exerted the same effects but also increased oedema volume estimated by MRI. Co-administration of AM281 and AM630 produced the effects observed with the administration of either AM281 or AM630 and also reduced white matter and myelin preservation and enhanced microgliosis in the epicentre. Overall, our results suggest that the endocannabinoids acting through CB1 and CB2 receptors are part of an early neuroprotective response triggered after SCI that is involved in the spontaneous recovery after an incomplete lesion.Angel Arevalo-MartinDaniel Garcia-OvejeroYolanda Sierra-PalomaresBeatriz Paniagua-TorijaInes Gonzalez-GilSilvia Ortega-GutierrezEduardo Molina-HolgadoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49057 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angel Arevalo-Martin Daniel Garcia-Ovejero Yolanda Sierra-Palomares Beatriz Paniagua-Torija Ines Gonzalez-Gil Silvia Ortega-Gutierrez Eduardo Molina-Holgado Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
description	Spinal cord injury (SCI) induces a cascade of processes that may further expand the damage (secondary injury) or, alternatively, may be part of a safeguard response. Here we show that after a moderate-severe contusive SCI in rats there is a significant and very early increase in the spinal cord content of the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (anandamide, AEA). Since 2-AG and AEA act through CB1 and CB2 cannabinoid receptors, we administered at 20 minutes after lesion a single injection of their respective antagonists AM281 and AM630 alone or in combination to block the effects of this early endocannabinoid accumulation. We observed that AM281, AM630 or AM281 plus AM630 administration impairs the spontaneous motor recovery of rats according to the Basso-Beattie-Bresnahan (BBB) locomotor scale. However, blockade of CB1, CB2 or both receptors produced different effects at the histopathological level. Thus, AM630 administration results at 90 days after lesion in increased MHC-II expression by spinal cord microglia/monocytes and reduced number of serotoninergic fibres in lumbar spinal cord (below the lesion). AM281 exerted the same effects but also increased oedema volume estimated by MRI. Co-administration of AM281 and AM630 produced the effects observed with the administration of either AM281 or AM630 and also reduced white matter and myelin preservation and enhanced microgliosis in the epicentre. Overall, our results suggest that the endocannabinoids acting through CB1 and CB2 receptors are part of an early neuroprotective response triggered after SCI that is involved in the spontaneous recovery after an incomplete lesion.
format	article
author	Angel Arevalo-Martin Daniel Garcia-Ovejero Yolanda Sierra-Palomares Beatriz Paniagua-Torija Ines Gonzalez-Gil Silvia Ortega-Gutierrez Eduardo Molina-Holgado
author_facet	Angel Arevalo-Martin Daniel Garcia-Ovejero Yolanda Sierra-Palomares Beatriz Paniagua-Torija Ines Gonzalez-Gil Silvia Ortega-Gutierrez Eduardo Molina-Holgado
author_sort	Angel Arevalo-Martin
title	Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
title_short	Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
title_full	Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
title_fullStr	Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
title_full_unstemmed	Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
title_sort	early endogenous activation of cb1 and cb2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/344bb135cc804e69a00299347a630684
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Early endogenous activation of CB1 and CB2 receptors after spinal cord injury is a protective response involved in spontaneous recovery.

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