Activation of MAP kinase (ERK-1/ERK-2), tyrosine kinase and VEGF in the human brain following acute ischaemic stroke

Citation
M. Slevin et al., Activation of MAP kinase (ERK-1/ERK-2), tyrosine kinase and VEGF in the human brain following acute ischaemic stroke, NEUROREPORT, 11(12), 2000, pp. 2759-2764
Citations number
27
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROREPORT
ISSN journal
09594965 → ACNP
Volume
11
Issue
12
Year of publication
2000
Pages
2759 - 2764
Database
ISI
SICI code
0959-4965(20000821)11:12<2759:AOMK(T>2.0.ZU;2-1
Abstract
We examined expression of vascular endothelial growth factor (VEGF), phosph orylation of mitogen activated protein kinase (MAP) kinase (ERK1 and ERK2) and tyrosine phosphorylation in 19 patients (aged 58-90 years; mean 75) who died 1-44 days after acute ischaemic stroke. in the grey matter penumbra, 13 of 19 patients showed an increase in MAP kinase tyrosine phosphorylation (ERK1; 2.0- to 8-fold, ERK2; 2.2- to 11-fold) compared with normal contral ateral tissue. in almost all cases, ERK-2 phosphorylation was higher than E RK1. Of these 13 patients, 11 also showed a general increase in tyrosine ki nase phosphorylation, and eight expressed increased levels of VEGF protein (2.5- to 5-fold). In tissue examined directly from the infarct core, activa tion of the above proteins was not observed in the, majority of patients. I n the white matter, seven of 19 patients (penumbra), and nine of 19 patient s (stroke) had an increase in MAP kinase tyrosine phosphorylation (ERK1; 2. 0- to 4.6-fold and ERK-2; 2.3- to 5.4-fold respectively) compared with norm al contralateral tissue. There was no relationship between activation of MA P kinase and expression of VEGF. Examination of phosphorylated MAP kinase b y immunohistochemistry revealed an increase in immunoreactivity in neurones , astroglial cells, reactive microglia and endothelial cells in areas surro unding infarcts, especially in areas with the highest density of microvesse ls. In conclusion, chronic activation of tyrosine phosphorylated events, in particular redistribution and phosphorylation of MAP kinase (ERK1/ERK2) oc curs consistently in the grey matter penumbra of brain tissue following isc haemic stroke, and may be associated with increase in expression of VEGF. T hese signal transduction events could be important determinants of the exte nt of neuronal survival and/or angiogenic activity in the recovering brain tissue. NeuroReport 11:2759-2764 (C) 2000 Lippincott Williams & Wilkins.