Proteomic analysis of global protein expression changes in the endothelin-1 rat model for cerebral ischemia: rescue effect of mild hypothermia.
Mild hypothermia is a promising neuroprotective therapy in stroke management. However, little is known about its effects on the global protein expression patterns in brain regions affected by ischemic stroke. We investigated protein expression changes associated with the neuroprotective effects of hypothermia via a functional proteomics approach through the analysis of the core (striatum) and the penumbra (cortex) after an ischemic insult in rats induced by endothelin-1 (Et-1). Functional outcome, infarct volume and related global protein expression changes were assessed 24h after the insult using two-dimensional difference gel electrophoresis. Mild hypothermia, induced 20 min after endothelin-1 infusion, improved the neurological outcome, reflected by a 36% reduction in infarct volume and a significantly better neurological deficit score. Hypothermia was typically associated with opposite protein expression changes inthe cortex to those induced by stroke under normothermic conditions, but not in the striatum. The main cellular processes rescued by hypothermia and potentially involved in the protection of the cortex are cellular assembly and organization, followed by cell signaling, thereby confirming that hypothermia is neuroprotective through multiple molecular and cellular pathways.
Department of Pharmaceutical Chemistry and Drug Analysis, Centre for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: Tine.Zgavc@vub.ac.be.
Tine
T
Zgavc
Tjing-Tjing
TT
Hu
Babs
B
Van de Plas
Mathieu
M
Vinken
An-Gaëlle
AG
Ceulemans
Said
S
Hachimi-Idrissi
Sophie
S
Sarre
Yvette
Y
Michotte
Lutgarde
L
Arckens
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000008:administration & dosage*; D007036:Hypothermia, Induced; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D057825:Two-Dimensional Difference Gel Electrophoresis
D019332:Endothelin-1; D009419:Nerve Tissue Proteins
2 dimensional difference gel electrophoresis; 2-D DIGE; 3-cholamidopropyl dimethylammonio 1 propanesulfonate; ACN; ANOVA; AP; BBB; BVA; CHAPS; Cerebral ischemia; DTT; Endothelin-1; Et-1; FA; H; HPLC; Hypothermia; IEF; IPA; IPG; MCA; MS; N; NDS; Proteomics; S; SDS; TBS; Tris buffered saline; acetonitrile; analysis of variance; anterior–posterior; biological variation analysis; blood brain barrier; dithiothreitol; endothelin-1; formic acid; high performance liquid chromatography; hypothermic; i.p.; immobilized pH gradient; ingenuity pathway analysis; intraperitoneal; isoelectric focusing; mass spectrometry; middle cerebral arterie; neurological deficit score; normothermic; recombinant tissue plasminogen activator; rt-PA; sham; sodium dodecyl sulfate