Neuroprotective Effects of Hydrogen Sulfide Against Early Brain Injury and Secondary Cognitive Deficits Following Subarachnoid Hemorrhage

Abstract

Although the neuroprotective effects of hydrogen sulfide (H S) have been demonstrated in several studies, whether H S protects against early brain injury (EBI) and secondary cognitive dysfunction in subarachnoid hemorrhage (SAH) model remains unknown. This study was undertaken to evaluate the influence of H S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H S donor, NaHS, was administered via an intraperitoneal injection at a dose of 5.6 mg/kg at 2 h, 6 h, 24 h, and 46 h after SAH in rat model. The results showed that NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation at 48 h after SAH. NaHS also promoted phospho-Akt and phospho-ERK levels. Furthermore, NaHS treatment significantly enhanced the levels of brain-derived neurotrophic factor (BDNF) and phospho-CREB. Importantly, NaHS administration improved learning and memory performance in the Morris water maze test at 7 days post-SAH in rats. These results demonstrated that NaHS, as an exogenous H S donor, could significantly alleviate the development of EBI and cognitive dysfunction induced by SAH via Akt/ERK-related antiapoptosis pathway, and upregulating BDNF-CREB expression.

Recombinant human brain-derived neurotrophic factor prevents neuronal apoptosis in a novel in vitro model of subarachnoid hemorrhage

“…BDNF polymorphisms predict a poor outcome in aneurysmal SAH patients 25. Moreover, BDNF was activated after cysteamine or N-acetyl serotonin derivative treatment in models of SAH 25,26. These data implicate the validity of our in vitro model, as well as the potential therapeutic effect of BDNF in SAH.…”

Neuroprotective Effects of a Smoothened Receptor Agonist against Early Brain Injury after Experimental Subarachnoid Hemorrhage in Rats

“…ERK phosphorylation also results in the phosphorylation of the pro-apoptotic Bim protein (McCubrey et al, 2007), and then prevents Bax activation. The previous studies reported that the phosphorylation of ERK was decreased in brain after SAH insult and increase of its expression was associated with ameliorating neuronal cell death (Lin et al, 2009; Li et al, 2016). In agreement with these studies, we found that SAH insult decreased p-ERK level, while treatment with PUR significantly enhanced ERK phosphorylation.…”

“…Experimental animals were subjected to SAH by double blood injection method according to previous study (Li et al, 2016). Firstly, deep anesthesia was induced under 3.5% isoflurane and maintained the anesthesia state at a concentration of 2.5%.…”

Functional and Molecular Insights of Hydrogen Sulfide Signaling and Protein Sulfhydration

“…NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl-2 ratio and suppression of caspase-3 activation after SAH [171]. …”