MR image-guided investigation of regional signal transducers and activators of transcription-1 activation in a rat model of focal cerebral ischemia.
OBJECTIVE
STAT-1 is a member of a family of proteins called signal transducers and activators of transcription (STATs), and recent studies have shown its involvement in the induction of apoptosis. There is limited information on the role of STAT-1 following stroke. In this study we use MRI measurements of cerebral perfusion and bioenergetic status to target measurements of regional STAT-1 activity.


METHODS
Rats were subjected to 60 or 90 min of middle cerebral artery occlusion with and without reperfusion. MRI maps of the apparent diffusion coefficient of water and cerebral blood flow were acquired throughout the study. After the ischemia or reperfusion period, the brain was excised and samples were analyzed by Western blots using anti-phospho-STAT1 and anti-Fas antibodies. Regions were selected for analysis according to their MRI characteristics.


RESULTS
Transcriptional factor STAT-1 was enhanced in the lesion core and, to a lesser extent, in the lesion periphery, following ischemia and reperfusion. This level of activity was greater than for ischemia alone. Western blots demonstrated STAT-1 phosphorylation on tyrosine 701 and not serine 727 after ischemia and 3 h of reperfusion. Enhanced expression of the apoptotic death receptor Fas was confirmed after ischemia followed by reperfusion.


CONCLUSIONS
This study demonstrates that focal ischemia of the rat brain can induce STAT-1 activation, particularly following a period of reperfusion. The activation occurs not only in the lesion core, but also in the lesion periphery, as identified using MRI. STAT-1 may play an important role in the induction of cell death following stroke.
West
D A
DA
Royal College of Surgeons Unit of Biophysics, Institute of Child Health, University College London, London WC1N 1EH, UK.
Valentim
L M
LM
Lythgoe
M F
MF
Stephanou
A
A
Proctor
E
E
van der Weerd
L
L
Ordidge
R J
RJ
Latchman
D S
DS
Gadian
D G
DG
D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D015534:Trans-Activators; D019014:fas Receptor; D014443:Tyrosine