Inhibition of apoptotic cell death by ghrelin improves functional recovery after spinal cord injury

Jee Y. Lee, Hyunju Chung, Young S. Yoo, Young Jun Oh, Tae H. Oh, Seungjoon Park, Tae Y. Yune

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Spinal cord injury (SCI) induces massive cell death, leading to permanent neurological disability. No satisfactory treatment is currently available. Ghrelin, a gastric hormone, is known to stimulate GH release from the hypothalamus and pituitary gland. Here, we report that ghrelin administration improves functional recovery after SCI in part by inhibiting apoptosis of neurons and oligodendrocytes. Ghrelin was not detected in normal, uninjured spinal cords, but spinal cord neurons and oligodendrocytes expressed the ghrelin receptor. Ghrelin significantly inhibited apoptotic cell death of neurons and oligodendrocytes, release of mitochondrial cytochrome c, and activation of caspase-3 after moderate contusion SCI. Ghrelin also significantly increased the level of phosphorylated ERK but decreased the level of phosphorylated p38MAPK. In addition, ghrelin increased the level of ERK-dependent brain-derived neurotrophic factor expression and decreased the level of pronerve growth factor expression. Furthermore, the neuroprotective effects of ghrelin were mediated through the ghrelin receptor. Finally, ghrelin significantly improved functional recovery and reduced the size of the lesion volume and the loss of axons and myelin after injury. These results suggest that ghrelin may represent a potential therapeutic agent after acute SCI in humans.

Original languageEnglish
Pages (from-to)3815-3826
Number of pages12
JournalEndocrinology
Volume151
Issue number8
DOIs
Publication statusPublished - 2010 Aug 1

Fingerprint

Ghrelin
Spinal Cord Injuries
Cell Death
Oligodendroglia
Ghrelin Receptor
Neurons
Spinal Cord
Contusions
Brain-Derived Neurotrophic Factor
Neuroprotective Agents
Pituitary Gland
Myelin Sheath
Cytochromes c
Caspase 3
Hypothalamus
Axons
Intercellular Signaling Peptides and Proteins
Stomach
Hormones
Apoptosis

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Lee, Jee Y. ; Chung, Hyunju ; Yoo, Young S. ; Oh, Young Jun ; Oh, Tae H. ; Park, Seungjoon ; Yune, Tae Y. / Inhibition of apoptotic cell death by ghrelin improves functional recovery after spinal cord injury. In: Endocrinology. 2010 ; Vol. 151, No. 8. pp. 3815-3826.
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Inhibition of apoptotic cell death by ghrelin improves functional recovery after spinal cord injury. / Lee, Jee Y.; Chung, Hyunju; Yoo, Young S.; Oh, Young Jun; Oh, Tae H.; Park, Seungjoon; Yune, Tae Y.

In: Endocrinology, Vol. 151, No. 8, 01.08.2010, p. 3815-3826.

Research output: Contribution to journalArticle

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