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
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.