Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury.
Traumatic human spinal cord injury (SCI) causes devastating and long-term hardships. These are due to the irreparable primary mechanical injury and secondary injury cascade. In particular, oligodendrocyte cell death, white matter axon damage, spared axon demyelination, and the ensuing dysfunction in action potential conduction lead to the initial deficits and impair functional recovery. For these reasons, and that oligodendrocyte and axon survival may be related, various neuroprotective strategies after spinal cord injury are being investigated. We previously demonstrated that oligodendrocytes in the adult rat epicenter ventrolateral funiculus (VLF) express 3'-5'-cyclic adenosine monophosphate-dependent phosphodiesterase 4 (PDE4) subtypes and that their death was attenuated up to 3 days after contusive cervical SCI when rolipram, a specific inhibitor of PDE4, was administered. Here, we report that (1) there are more oligodendrocyte somata in the adult rat epicenter VLF, (2) descending and ascending axonal conductivity in the VLF improves, and that (3) there are fewer hindlimb footfall errors during grid-walking at 5 weeks after contusive cervical SCI when rolipram is delivered for 2 weeks. This is the first demonstration of improved descending and ascending long-tract axonal conductivity across a SCI with this pharmacological approach. Since descending long-tract axonal conductivity did not return to normal, further evaluations of the pharmacokinetics and therapeutic window of rolipram as well as optimal combinations are necessary before consideration for neuroprotection in humans with SCI.
Beaumont
E
E
Kentucky Spinal Cord Injury Research Center, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
Whitaker
C M
CM
Burke
D A
DA
Hetman
M
M
Onifer
S M
SM
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D002574:Cervical Vertebrae; D005260:Female; D009413:Nerve Fibers, Myelinated / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D020889:Rolipram / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D016138:Walking
D018696:Neuroprotective Agents; D020889:Rolipram