Curcumin protects against stroke and increases levels of Notch intracellular domain.
OBJECTIVE
To investigate whether curcumin regulates Notch signaling to cause neuroprotection and neurogenesis after focal ischemia reperfusion injury.


METHODS
Focal ischemia reperfusion injury was modeled in rats by occluding the middle cerebral artery. These animals were given either curcumin (300 mg/kg) or corn oil (vehicle) by intraperitoneal injection starting 1 h after stroke and continuing for 7 d. In parallel, sham-operated control animals received vehicle. All animals were killed on day 12. The different treatment groups were compared in terms of neurobehavioral deficits, BrdU incorporation, and levels of doublecortin (DCX) and Notch intracellular domain (NICD) using immunohistochemistry, immunofluorescence and Western blotting.


RESULTS
Animals treated with curcumin showed significantly smaller neurobehavioral deficits than vehicle-treated animals after 3, 7, and 12 d of reperfusion (all p < 0.05). Tissue sections from curcumin-treated animals contained significantly greater numbers of BrdU-positive cells (p < 0.05) and BrdU/DCX-positive cells (p < 0.01), as well as significantly higher NICD levels (p < 0.01).


CONCLUSIONS
Curcumin may protect from focal cerebral ischemia reperfusion injury as well as stimulate neurogenesis by activating the Notch signaling pathway.
a Department of Neurology , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Shuang
S
Liu
a Department of Neurology , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Yungang
Y
Cao
a Department of Neurology , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Man
M
Qu
b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Zheng
Z
Zhang
b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Liang
L
Feng
b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Zusen
Z
Ye
b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Meijuan
M
Xiao
c Institute for Biological Sciences , National Research Council Canada , Ottawa , Canada.
Sheng T
ST
Hou
b Department of Neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Rongyuan
R
Zheng
a Department of Neurology , The Second Affiliated Hospital of Wenzhou Medical University , Wenzhou , China.
Zhao
Z
Han
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002552:Cerebral Ventricles / Q000166:cytology / Q000187:drug effects; D003474:Curcumin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D055495:Neurogenesis / Q000187:drug effects; D009460:Neurologic Examination; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D051880:Receptors, Notch; D001973:Bromodeoxyuridine; D003474:Curcumin
BrdU; Curcumin; Middle cerebral artery occlusion; Neurogenesis; Neuroprotection; Notch