[Parthenolide inhibits neuroinflammation and promotes neurogenesis in the ischemic striatum following transient middle cerebral artery occlusion in the adult rat brain].
OBJECTIVE
The objective of this study was to test the hypothesis that parthenolide suppresses ischemia-induced neuroinflammation in the MCAO model of adult rat.


METHODS
MCAO rats were treated i.p. with parthenolide (500 microg/kg). Brain sections were analyzed for BrdU, BrdU-DCX, BrdU-Tuj-1, BrdU-MAP-2 and BrdU-GFAP staining. Total protein was extracted from ischemic striatum, and Western blot was used to determine TNF-alpha expression.


RESULTS
Cerebral ischemia increases expression of TNF-alpha in the ischemic striatum. Parthenolide suppressed the expression of TNF-alpha and enhances the proliferation of newborn cells in the ischemic striatum. The cell number of BrdU(+)-DCX(+), BrdU(+)-Tuj-1(+), and BrdU(+)-MAP-2(+) is increased in the ischemic striatum after parthenolide treatment at 3 d, 7 d or 28 d after MCAO. Furthermore, parthenolide depressed the cell number of BrdU(+)-GFAP(+) in the ischemic striatum at 3 d, 7 d and 28 d after MCAO.


CONCLUSIONS
Parthenolide inhibits neuroinflammation induced by cerebral ischemia and promotes neurogenesis in the ischemic striatum. Further study of the effects of parthenolide on inflammatory gene expression using model animal systems as described here are critical to elucidating their mechanisms of action.
Lei
Zhi-nian
ZN
Department of Human Anatomy, Southeast University, Nanjing 210009, China. zhinianlei@gmail.com
Zeng
Shui-lin
SL
Wang
Lei
L
Zhu
Jian-bao
JB
Li
Tao
T
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D000089662:Doublecortin Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007511:Ischemia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; C002669:parthenolide; D001973:Bromodeoxyuridine