Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury.
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.
Whitaker
Christopher M
CM
Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
Beaumont
Eric
E
Wells
Michael J
MJ
Magnuson
David S K
DS
Hetman
Michal
M
Onifer
Stephen M
SM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002574:Cervical Vertebrae; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology* / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology
D039481:CD11b Antigen; C509295:ITGAM protein, human; D007527:Isoenzymes; D018696:Neuroprotective Agents; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human; D020889:Rolipram