Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage

Abstract

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4%. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative. Key words: subarachnoid hemorrhage, vasospasm, N-acetylcysteine.Efeito da N-acetilcisteína sobre o vasoespasmo na hemorragia subaracnóidea RESUMO O vasoespasmo arterial encefálico continua sendo uma complicação extremamente grave que acomete pacientes com hemorragia subaracnóidea (HSA) por ruptura de aneurismas. O arsenal terapêutico atual ainda, em muitos casos, é insuficiente e a busca de novas alternativas terapêuticas torna-se necessária. Neste estudo, avaliamos a ação da N-acetilcisteína (NAC) sobre o vasoespasmo arterial encefálico em um modelo experimental. Foram utilizados 24 ratos wistar divididos em 4 grupos:HSA+Placebo. O modelo experimental utilizado foi o da dupla injeção subaracnóidea de sangue autólogo. A dose proposta da NAC foi de 250 mg/kg/dia por via intraperitoneal. Foi analisada a área interna da artéria basilar para avaliação da ação da NAC. O modelo experimental mostrou-se excelente com mortalidade de 4%. A mensuração da área interna da artéria basilar do grupo HSA demonstrou diminuição significativa em relação ao grupo controle (p=0,009). A administração da NAC reduziu significativamente

Neuroprotective Agents in the Intensive Care Unit

“…NAC can cross BBB, depending on the route of administration and the dosage of the drug [ 148 ]. The decrease of cerebral vasospasm is reported in a human patients and animal models with Subarachnoid hemorrhage after administration of NAC [ 148 , 153 , 154 ]. The beneficial effect of NAC has been reported in acute ischemic and hemorrhagic stroke and TBI in rodents [ 149 , 152 – 155 ].…”

Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications

“…Given its role as the principal upstream mediator of NOS-2 expression in SAH, NF-κB seems an obvious target. Several compounds demonstrating preclinical benefit in SAH including the hormone estradiol[ 137 ] and the antioxidant N-acetyl cysteine[ 138 139 ] exploit this mechanism to block NOS-2 upregulation. However, one potential problem with NF-κB blockade is timing.…”

Pharmacologic Management of Subarachnoid Hemorrhage

“…6-mercaptopurine (6-mp) has been demonstrated to suppress the production of serum IL-1, IL-6, TNF-α, and CSF ET-1 in a SAH rat model dose-dependently (Pereira Filho Nde et al, 2010). This action is proposed to mediate the differentiation and metabolism of hematopoietic cells and glia after SAH .…”

“…The protective effect of N-acetylcysteine (NAC), a sulfhydryl-containing moiety markedly reversed SAH-induced neurological deficit and brain oedema in a wister rat model (Pereira Filho Nde et al, 2010). NAC works to upregulate copper/zinc-superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activity and decrease malondialdehyde (MDA) content after SAH (Guney et al, 2010).…”