Spontaneous subarachnoid hemorrhage (SAH), which results from the rupture of intracranial aneurysms, is a prevalent acute cerebrovascular condition [1]. SAH poses a significant menace to worldwide public health, with a pre-hospital mortality rate ranging from 22% to 26% [2]. Additionally, a considerable proportion of SAH survivors, approximately fifty percent, experience enduring neurological impairment [3]. Despite the effectiveness of surgery in preventing rebleeding, the clinical prognosis of patients with SAH has not been significantly improved [4,5]. Consequently, it is imperative to thoroughly examine the key mechanisms underlying neurological damage following SAH and identify potential intervention therapies to ameliorate such injuries. The release of hemoglobin (Hb) from lysed erythrocytes has been identified as the primary catalyst for neuronal damage following SAH. The significant presence of iron ions derived from Hb creates a hemorrhagic microenvironment within the subarachnoid space. These surplus iron ions predominantly accumulate in nerve cells via the transferrin-transferrin receptor transport system, which subsequently undergoes the Fenton reaction. This reaction leads to the interaction between iron ions and hydrogen peroxide, resulting in the formation of excessive amounts of highly toxic hydroxyl groups and reactive oxygen species (ROS). Ultimately, this process induces neuronal ferroptosis [6,7]. Furthermore, neuroinflammation serves as another significant factor contributing to neuronal injury [8,9]. Specifically, damage-associated molecular patterns (DAMPs) originating from Hb play a crucial role in activating microglia through Toll-like receptor 4 (TLR4), subsequently leading to the release of inflammatory factors [10,11]. These inflammatory factors, further stimulated by iron ion-induced ROS [12,13], result in impairment of the blood-brain barrier, cerebral vasospasm, and programmed neuronal death [11,14,15].

Notably, hydrogen has emerged as an ideal therapeutic gas with potent antioxidative stress properties and has been successfully employed in various clinical applications in the central nervous system (CNS) [[16], [17], [18], [19]]. Our preliminary experiments demonstrated the neuroprotective effects of hydrogen in SAH, as it effectively suppressed oxidative stress [20,21], which has been reaffirmed by groups from Japan and the United States [22,23]. However, the mechanism through which hydrogen inhibits neuronal death remains unclear. Further studies are required to elucidate the involvement of hydrogen in the regulation of oxidative stress-induced ferroptosis in SAH. Hence, the primary objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH by examining its inhibitory effects on ferroptosis and neuroinflammation.