N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage☆

Abstract 

Background

This study investigated the ability of NAC to prevent cerebral vasospasm in a rabbit model of SAH.

Methods

Twenty-one, male New Zealand white rabbits were randomly divided into 3 groups of 7 rabbits each: group 1 (control), group 2 (SAH only), group 3 (SAH + NAC treatment). NAC (150 mg/kg, single dose, IP) was administered just before SAH and continued until 72 hours after SAH in group 3.

Animals were killed 72 hours after SAH. Tissue MDA levels, SOD, and GSH-Px activities were measured, and basilar artery cross-sectional areas, arterial wall thickness, and endothelial apoptosis in a cross section of basillary artery were determined in all groups.

Results

Intraperitoneal administration of NAC was found to be markedly effective against developing a cerebral vasospasm following a SAH in rabbits. It could significantly reduce elevated lipid peroxidation and increase the level of tissue GSH-Px and SOD enzymatic activities. Also, NAC treatment was found to be effective in increasing the luminal area and reducing wall thickness of the basilar artery. The morphology of arteries in the NAC treatment group was well protected. NAC markedly reduced apoptotic index and protects the endothelial integrity.

Conclusions

This study demonstrates, for the first time, that NAC treatment attenuates cerebral vasospasm in a rabbit SAH model. NAC treatment has significant neuroprotective effect and markedly prevents cerebral vasospasm after SAH. In conclusion, the NAC treatment might be beneficial in preventing cerebral vasospasm after SAH, thus showing potential for clinical implications.

Abbreviations: CSF, Cerebrospinal fluid, GSH, Glutathione, GSH-Px, GSH peroxidase, GSSG, oxidized GSH, GR, GSH reductase, INT, 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazolium chloride, MDA, Malondialdehyde, NAC, N-acetylcysteine, PBS, Phosphate-buffered saline, SAH, Subarachnoid hemorrhage, SOD, Superoxide dismutase, TdT, Terminal deoxynucleotidyl transferase, XOD, Xanthine oxidase

Keywords: N-acetylcysteine, Subarachnoid hemorrhage, Vasospasm, Rabbit