Journal
NEUROSCIENCE LETTERS
Volume 438, Issue 2, Pages 200-204Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.03.087
Keywords
cAMP; phosphodiesterase 4; white matter; APC; OX-42; microglia
Categories
Funding
- NCRR NIH HHS [P20 RR015576, P20 RR015576-019002, P20 RR015576-059003, P20 RR015576-050005, P20 RR015576-03S19002, P20 RR015576-049002, P20 RR015576-039002, P20 RR015576-029002, RR15576] Funding Source: Medline
- NINDS NIH HHS [R01 NS040411, R01 NS047341, NS40411, R01 NS040411-02, NS047341, R01 NS040411-03, R01 NS040411-01, R01 NS047341-05, R01 NS040411-05, R01 NS040411-04] Funding Source: Medline
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Rolipram, an inhibitor of phosphodiesterase 4 (PDE4) proteins that hydrolyze cAMP, increases axonal regeneration following spinal cord injury (SCI). Recent evidence indicate that rolipram also protects against a multitude of apoptotic signals, many of which are implicated in secondary cell death post-SCI. In the present study, we used immunohistochemistry and morphometry to determine potential spinal cord targets of rolipram and to test its protective potential in rats undergoing cervical spinal cord contusive injury. We found that 3 PDE4 subtypes (PDE4A, B, D) were expressed by spinal cord oligodendrocytes. OX-42 immunopositive microglia only expressed the PDE4B subtype. Oligodendrocyte somata were quantified within the cervical ventrolateral funiculus, a white matter region critical for locomotion, at varying time points after SCI in rats receiving rolipram or vehicle treatments. We show that rolipram. significantly attenuated oligodendrocyte death at 24 h post-SCI continuing through 72 h, the longest time point examined. These results demonstrate for the first time that spinal cord glial cells express PDE4 subtypes and that the PDE4 inhibitor rolipram, protects oligodendrocytes from secondary cell death following contusive SCI. They also indicate that further investigations into neuroprotection and axonal regeneration with rolipram are warranted for treating SCI. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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