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Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke

Cheng, Xiaowen LU ; Boza-Serrano, Antonio LU ; Turesson, Michelle Foldschak; Deierborg, Tomas LU ; Ekblad, Eva LU and Voss, Ulrikke LU (2016) In Scientific Reports 6.
Abstract

In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3 +/+, but not in galectin-3 mice. In vitro we show that serum from galectin-3 +/+, but not from galectin-3 mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4 mice were unaffected. Further purified galectin-3 (10 6 M)... (More)

In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3 +/+, but not in galectin-3 mice. In vitro we show that serum from galectin-3 +/+, but not from galectin-3 mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4 mice were unaffected. Further purified galectin-3 (10 6 M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3 +/+ pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84986880504
  • wos:000391987700001
ISSN
2045-2322
DOI
10.1038/srep32893
language
English
LU publication?
yes
id
fa96fa73-ec97-4ce6-92cc-c08c236ee883
date added to LUP
2016-11-04 14:19:50
date last changed
2017-09-18 11:29:24
@article{fa96fa73-ec97-4ce6-92cc-c08c236ee883,
  abstract     = {<p>In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3 +/+, but not in galectin-3 mice. In vitro we show that serum from galectin-3 +/+, but not from galectin-3 mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4 mice were unaffected. Further purified galectin-3 (10 6 M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3 +/+ pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.</p>},
  articleno    = {32893},
  author       = {Cheng, Xiaowen and Boza-Serrano, Antonio and Turesson, Michelle Foldschak and Deierborg, Tomas and Ekblad, Eva and Voss, Ulrikke},
  issn         = {2045-2322},
  language     = {eng},
  month        = {09},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke},
  url          = {http://dx.doi.org/10.1038/srep32893},
  volume       = {6},
  year         = {2016},
}