Rolipram, a phosphodiesterase type IV inhibitor, exacerbates periventricular white matter lesions in rat pups

Ying Chao Chang, Chao Ching Huang, Pi Lien Hung, Hsiu Mei Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Periventricular white matter injury is the leading cause of cerebral palsy in premature infants for which no effective treatments are available. Our previous studies have demonstrated that pharmacological activation of the cAMP response element-binding protein (CREB) signaling pathway, before hypoxic-ischemia protected against neuronal injury in neonatal rats. We examined whether rolipram, a phosphodiesterase type IV inhibitor, treatment after hypoxic-ischemia is protective against white matter injury in neonatal rats. Rats were exposed to hypoxia-ischemia (HI) on P7 and then treated with daily injections of various doses of rolipram (P7-P11). Immunohistochemical staining for myelin basic protein, ED1, glial fibrillary acidic protein, CREB and O1 were examined on P11. We found that the periventricular white matter and deep cortical lesions were exacerbated by rolipram administration after HI injury. The lesions in the rolipram-treated group also showed increased astrogliosis and increased CREB phosphorylation in the activated microglia and astrocytes. Furthermore, the rolipram-posttreated HI group had markedly depleted preoligodendrocytes in the ipsilateral hemisphere, which may be related to decreased preoligodendrocytes proliferation after rolipram treatment per se. These data suggest that rolipram treatment after hypoxic-ischemia is not protective; in contrast, rolipram may exacerbate hypoxic-ischemic white matter injury in neonatal rat brains.

Original languageEnglish
Pages (from-to)234-239
Number of pages6
JournalPediatric Research
Volume64
Issue number3
DOIs
Publication statusPublished - Sep 2008
Externally publishedYes

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Type 4 Cyclic Nucleotide Phosphodiesterase
Rolipram
Phosphodiesterase Inhibitors
Ischemia
Cyclic AMP Response Element-Binding Protein
Wounds and Injuries
Myelin Basic Protein
White Matter
Glial Fibrillary Acidic Protein
Microglia
Cerebral Palsy
Therapeutics
Premature Infants
Astrocytes
Phosphorylation
Pharmacology
Staining and Labeling
Injections

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Rolipram, a phosphodiesterase type IV inhibitor, exacerbates periventricular white matter lesions in rat pups. / Chang, Ying Chao; Huang, Chao Ching; Hung, Pi Lien; Huang, Hsiu Mei.

In: Pediatric Research, Vol. 64, No. 3, 09.2008, p. 234-239.

Research output: Contribution to journalArticle

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