TY - JOUR
T1 - Trefoil Factor 3 as an Endocrine Neuroprotective Factor from the Liver in Experimental Cerebral Ischemia/Reperfusion Injury
AU - Liu, Shu Q.
AU - Roberts, Derek
AU - Zhang, Brian
AU - Ren, Yupeng
AU - Zhang, Li Qun
AU - Wu, Yu H.
PY - 2013/10/18
Y1 - 2013/10/18
N2 - Cerebral ischemia, while causing neuronal injury, can activate innate neuroprotective mechanisms, minimizing neuronal death. In this report, we demonstrate that experimental cerebral ischemia/reperfusion injury in the mouse causes upregulation of the secretory protein trefoil factor 3 (TFF3) in the hepatocyte in association with an increase in serum TFF3. Partial hepatectomy (~60% liver resection) immediately following cerebral injury significantly lowered the serum level of TFF3, suggesting a contribution of the liver to the elevation of serum TFF3. Compared to wild-type mice, TFF3-/- mice exhibited a significantly higher activity of caspase 3 and level of cell death in the ischemic cerebral lesion, a larger fraction of cerebral infarcts, and a smaller fraction of the injured cerebral hemisphere, accompanied by severer forelimb motor deficits. Intravenous administration of recombinant TFF3 reversed changes in cerebral injury and forelimb motor function due to TFF3 deficiency. These observations suggest an endocrine neuroprotective mechanism involving TFF3 from the liver in experimental cerebral ischemia/reperfusion injury.
AB - Cerebral ischemia, while causing neuronal injury, can activate innate neuroprotective mechanisms, minimizing neuronal death. In this report, we demonstrate that experimental cerebral ischemia/reperfusion injury in the mouse causes upregulation of the secretory protein trefoil factor 3 (TFF3) in the hepatocyte in association with an increase in serum TFF3. Partial hepatectomy (~60% liver resection) immediately following cerebral injury significantly lowered the serum level of TFF3, suggesting a contribution of the liver to the elevation of serum TFF3. Compared to wild-type mice, TFF3-/- mice exhibited a significantly higher activity of caspase 3 and level of cell death in the ischemic cerebral lesion, a larger fraction of cerebral infarcts, and a smaller fraction of the injured cerebral hemisphere, accompanied by severer forelimb motor deficits. Intravenous administration of recombinant TFF3 reversed changes in cerebral injury and forelimb motor function due to TFF3 deficiency. These observations suggest an endocrine neuroprotective mechanism involving TFF3 from the liver in experimental cerebral ischemia/reperfusion injury.
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U2 - 10.1371/journal.pone.0077732
DO - 10.1371/journal.pone.0077732
M3 - Article
C2 - 24204940
AN - SCOPUS:84885746397
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 10
M1 - e77732
ER -