The attenuation of vasospasm by using a sod mimetic after experimental subarachnoidal haemorrhage in rats.
BACKGROUND
Delayed cerebral vasoconstriction and brain ischemia, are critical problems in the management of a patient affected by rupture of an intracranial aneurysm. Overexpression of Cu-Zn superoxide dismutase (Cu-Zn SOD) can reduce the extent of cerebral vasospasm. We, therefore investigated if vasospasm, can be prevented by a novel, stable, and cell permeable SOD mimetic, MnTBAP [Mn(III) tetrakis (4-benzoic acid) porphyrin] which permeates the biological membranes and scavenges superoxide anions and peroxynitrite.


METHODS
28 rats (225-250 g) were divided equally into four groups: group 1: control; group 2: SAH only; group 3: SAH plus placebo; and group 4: SAH plus MnTBAP. We used a double haemorrhage method to produce SAH. Starting six hours after SAH, 5 mg/kg MnTBAP (Calbiochem, Darmstadt-Germany; Cat. No 475870)) or an equal volume of 0.9% saline (37 degrees C) was administered by intraperitoneal injection twice daily for 5 days to groups 4 and 3 respectively. MnTBAP or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed on the fifth day. Brain sections at the level of the pons were examined by light microscopy. Planimetric measurements were made for the cross-sectional areas of the lumen and the vessel wall (intima plus media) of the basilar artery by a micrometer.


RESULTS
Administration of MnTBAP significantly attenuated the vasoconstriction of the basilar artery in group 4 compared with the groups 2 and 3 (p<0.001).


CONCLUSIONS
These results suggest that this SOD mimetic (MnTBAP) attenuates delayed cerebral vasoconstriction following experimental SAH and that superoxide anions have a role in the pathogenesis of vasospasm after SAH.
Aladag
M A
MA
Department of Neurosurgery, Medical School of Inonu University, Turgut Ozal Medical Center, 44069 Malatya, Turkey. marifaladag@hotmail.com
Turkoz
Y
Y
Sahna
E
E
Parlakpinar
H
H
Gul
M
M
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D040761:Biomimetic Materials / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D013997:Time Factors; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D016166:Free Radical Scavengers; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013482:Superoxide Dismutase