JOURNAL ARTICLE

Valproate reduces CHOP levels and preserves oligodendrocytes and axons after spinal cord injury

C Penas, E Verdú, E Asensio-Pinilla, M S Guzmán-Lenis, M Herrando-Grabulosa, X Navarro, C Casas
Neuroscience 2011 March 31, 178: 33-44
21241777
Spinal cord injury (SCI) is a major cause of disability to which there are not yet effective treatments. We previously reported that degeneration of oligodendrocytes and neurons that occurs after SCI is associated with the development of endoplasmic reticulum (ER) stress and the progressive accumulation of the pro-apoptotic factor CHOP. Since following ER stress, the balance between the pro-survival chaperone BiP and CHOP drives the cell destiny, we aimed to find drugs that modulate this ratio in favour of the former. We found that valproate (VPA) induced a significant reduction of CHOP levels after ER stress in an organotypic-based culture of spinal cord in vitro. We then administered different doses of VPA to rats following spinal cord contusion, and found that the treatment caused a marked reduction of CHOP levels early after the lesion. In addition, VPA administration partially prevented cord tissue, myelin and axonal loss, and significantly increased the relative number of surviving oligodendrocytes in the damaged spinal cord. Besides, VPA-treated rats showed better recovery of the locomotor activity than vehicle-treated rats after SCI. Since VPA is a drug already in clinical use, these results open the avenue for its therapeutical use in SCI as well as in demyelinating disorders.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
21241777
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"