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Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury.

ABSTRACT: 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.

SUBMITTER: Whitaker CM

PROVIDER: S-EPMC2530896 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury.

Whitaker Christopher M CM Beaumont Eric E Wells Michael J MJ Magnuson David S K DS Hetman Michal M Onifer Stephen M SM

Neuroscience letters 20080408 2

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 ...[more]

PMID: 18455876

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Project description:It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR?375?3p and miR?1?3p) and downregulated (miR?363?3p, miR?449a?5p and miR?3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR?375 and miR?1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR?363, miR?449a and miR?3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR?375?3p, miR?1?3p, miR?363?3p, miR?449a?5p and miR?3074.

Dataset Information

Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury.

Publications

Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury.

Similar Datasets

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