Galectin-1-secreting neural stem cells elicit long-term neuroprotection against ischemic brain injury.

Abstract

Galectin-1 (gal-1), a special lectin with high affinity to β-galactosides, is implicated in protection against ischemic brain injury. The present study investigated transplantation of gal-1-secreting neural stem cell (s-NSC) into ischemic brains and identified the mechanisms underlying protection. To accomplish this goal, secretory gal-1 was stably overexpressed in NE-4C neural stem cells. Transient cerebral ischemia was induced in mice by middle cerebral artery occlusion for 60 minutes and s-NSCs were injected into the striatum and cortex within 2 hours post-ischemia. Brain infarct volume and neurological performance were assessed up to 28 days post-ischemia. s-NSC transplantation reduced infarct volume, improved sensorimotor and cognitive functions, and provided more robust neuroprotection than non-engineered NSCs or gal-1-overexpressing (but non-secreting) NSCs. White matter injury was also ameliorated in s-NSC-treated stroke mice. Gal-1 modulated microglial function in vitro, by attenuating secretion of pro-inflammatory cytokines (TNF-α and nitric oxide) in response to LPS stimulation and enhancing production of anti-inflammatory cytokines (IL-10 and TGF-β). Gal-1 also shifted microglia/macrophage polarization toward the beneficial M2 phenotype in vivo by reducing CD16 expression and increasing CD206 expression. In sum, s-NSC transplantation confers robust neuroprotection against cerebral ischemia, probably by alleviating white matter injury and modulating microglial/macrophage function.

• Authors: Jiayin Wang, Jinchao Xia, Feng Zhang, Yejie Shi, Yun Wu, Hongjian Pu, Anthony K F Liou, Rehana K Leak, Xinguang Yu, Ling Chen, Jun Chen
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 9621 (Apr 10 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 25858671 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytokines
• Galectin 1
• Nitric Oxide

Topics

• Animals
• Behavior, Animal
• Brain Ischemia (immunology, metabolism, pathology, therapy)
• Cell Survival
• Cerebral Infarction (pathology, therapy)
• Corpus Callosum (pathology)
• Corpus Striatum (pathology)
• Cytokines (biosynthesis)
• Galectin 1 (metabolism)
• Macrophages (metabolism)
• Mice
• Microglia (metabolism)
• Neural Stem Cells (metabolism)
• Nitric Oxide (metabolism)
• Phagocytosis
• Phenotype
• Psychomotor Performance
• Stem Cell Transplantation
• Time Factors
• White Matter (pathology)