Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia.
OBJECTIVE
Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI).


METHODS
Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days.


RESULTS
The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially.


CONCLUSIONS
Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.
Lennmyr
F
F
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University Hospital, Uppsala, Sweden. fredrik.lennmyr@surgsci.uu.se
Ericsson
A
A
Gerwins
P
P
Ahlström
H
H
Terént
A
A
D000818:Animals; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D007093:Imidazoles / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases
D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580