Hydrogen Sulfide Reduces Cognitive Impairment in Rats After Subarachnoid Hemorrhage by Ameliorating Neuroinflammation Mediated by the TLR4/NF-κB Pathway in Microglia

Abstract

Background and Aims: Cognitive impairment is one of the major complications of subarachnoid hemorrhage (SAH) and is closely associated with neuroinflammation. Hydrogen sulfide (H 2 S) has been shown to have an anti-inflammatory effect and reduce cognitive impairment in neurodegenerative diseases, but its effects in SAH have been little studied. This study aimed to investigate the effects of H 2 S on cognitive impairment after SAH and the possible underlying mechanisms. Methods: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into three groups: a sham group, a SAH group, and a SAH + NaHS (an H 2 S donor) group. The endovascular perforation technique was used to establish the experimental SAH model. NaHS was administered intraperitoneally. An active avoidance test (AAT) was performed to investigate cognitive function. The expression of TNF-α, toll-like receptor 4 (TLR4), and NF-κB p65 in the hippocampus was measured by Western blot and immunohistochemistry. The types of cells expressing TNF-α were detected by double immunofluorescence staining. Results: Compared to that in the sham group, the learning and memory ability of rats in the SAH group was damaged. Furthermore, the expression of TNF-α, TLR4, and NF-κB p65 in the hippocampus was elevated in the SAH group (p < 0.05). TNF-α was mainly expressed in activated microglia, which was consistent with the expression of TLR4. Treatment with NaHS significantly decreased the cognitive impairment of rats after SAH and simultaneously reduced the expression of TNF-α, TLR4, and NF-κB p65 and alleviated the nuclear translocation of NF-κB p65 (p < 0.05). Conclusions: The neuroinflammation reaction in microglia contributes to cognitive impairment after SAH. H 2 S reduced the cognitive impairment of rats after SAH by ameliorating neuroinflammation in microglia, potentially via the TLR4/NF-κB pathway.

Role of hydrogen sulfide in subarachnoid hemorrhage

“…75 Toll-like receptor 4 (TLR4) is widely expressed on the surface of glial cells, such as microglia, astrocytes, and oligodendrocytes in the CNS, and it plays an important role in the inflammatory response once activated by hemoglobin and its derivatives after SAH. [76][77][78] Duan et al 79 reported that NaHS treatment potentially alleviates neuroinflammation in microglia via the TLR4/ NF-κB pathway. To summarize, there is evidence that H 2 S alleviates neuroinflammation after SAH, but there are few reports on the underlying mechanism, and more in-depth studies should be conducted.…”

Unraveling Pathophysiological Link Between Mitophagy Pathway and Vascular Dementia

“…Researchers have used ischemic rodent models, including chronic and focal hypoperfusion, subarachnoid hemorrhage, and cerebral ischemia-reperfusion, to understand vascular changes related to cognitive impairment (30)(31)(32)(33). These models can be used to elucidate the pathophysiology of VaD.…”

Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations—A Short Overview

“…On the other hand, curcumin, a herbal extract from the roots of Curcuma longa, apparently mitigates inflammation by inhibiting the TLR4 axis, thereby polarizing microglia towards the M2 phenotype [ 66 ]. In a similar study, hydrogen sulfide reduced neuroinflammation by inhibiting TLR4/NF- κ B signaling in microglia, although its effects on vasospasm were not investigated [ 67 ]. Apigenin might suppress TLR4 activation, thereby restricting microglia-mediated apoptosis and inflammation while protecting against BBB disruption [ 68 ].…”