Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm.

Abstract

The exact underlying pathogenic mechanisms and effective preventive or therapeutic interventions for cerebral vasospasm remain obscure. The thioredoxin (Trx) system performs important functions in the central nervous system including neurotrophic and neuroprotective actions. There is no study directly investigating the effects of subarachnoid hemorrhage (SAH) induced cerebral vasospasm on the Trx system in the literature. Sixteen male New Zealand rabbits were randomly divided into two groups of eight rabbits each: a control group and a SAH group. The control group, (n = 8) was a sham surgery group in which SAH was not induced. In the SAH group, (n = 8), the SAH protocol was used to induce cerebral vasospasm. The brain and brainstem were removed and each brainstem was cut coronally into two pieces: an anterior part that contains basilar artery and a dorsal part that contains brainstem tissue. The brainstem tissue thioredoxin-1(Trx1), thioredoxin-2 (Trx2), thioredoxin reductase (TrxR), thioredoxin reductase-1 (TrxR1), thioredoxin-interacting protein (TXNIP) levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde levels (MDA) and tumor necrosis factor alpha (TNF-alpha) levels were investigated for determining the oxidative-antioxidative status of the related brain tissues. Basilar artery segments were investigated for cross-sectional area and wall thickness measurements. SAH statistically significantly reduced the tissue levels of Trx1 (p < 0.01) and TrxR (p < 0.01). Trx2 levels were not significantly altered after SAH (p > 0.05). SAH significantly reduced the expression of TrxR1 (p < 0.01) and significantly increased the expression of TXNIP (p < 0.01) when compared with controls. TOS levels and MDA levels significantly increased after SAH (p < 0.01) and TAS levels significantly reduced after SAH (p < 0.01). TNF-alpha levels significantly increased after SAH (p < 0.01). SAH-induced cerebral vasospasm significantly (p < 0.05) increased the wall thickness and reduced the mean cross-sectional area of the basilar artery (p < 0.05). The Trx system seems to be negatively affected by the simultaneously interrelated enzymatic alterations during cerebral vasospasm.