Citicoline inhibits MAP kinase signalling pathways after focal cerebral ischaemia.
The link between membrane phospholipids and different intracellular signal transduction pathways affected by cerebral ischaemia is unclear. CDP-choline, a major neuronal membrane lipid precursor and its intracellular target proteins and transcription factors were studied to further understand its role in ischaemic stroke. Cerebral ischaemia was produced by distal, permanent occlusion of the middle cerebral artery (MCAO) in the rat. Animals receiving 500 mg/kg of CDP-choline in 0.5 ml of 0.9% saline, intraperitoneally, 24 h and 1 h before MCAO and 23 h after MCAO demonstrated a notable reduction in the phosphorylation of MAP-kinase family members, ERK1/2 and MEK1/2, as well as Elk-1 transcription factor, compared with control animals treated with 0.5 ml of 0.9% saline. Immunohistochemistry showed a particular reduction in immunoreactivity in glia. The effects of CDP-choline on intracellular mechanisms of signal transduction, suggests that this molecule may play a key role in recovery after ischaemic stroke.
Krupinski
J
J
Cardiovascular Research Center, IIBB/CSIC-HSCSP-UAB, St.pau hospital, Barcelona, Spain.
Slevin
M
M
Badimon
L
L
D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline; D020928:Mitogen-Activated Protein Kinases