IL-32γ Plays a Neuroprotective Role after Acute Stroke in Middle Cerebral Artery Occlusion Mouse Model

Abstract

Stroke is the second leading cause of death and a major cause of long-term disability worldwide. Within minutes of onset, cerebral ischemia triggers a cascade of pathophysiological events that ultimately result in irreversible tissue damage. Post-ischemic inflammation plays a critical role in cerebral ischemia-reperfusion injury, characterized by the elevated release of cytokines and chemokines. Interleukin (IL)-32 is known to induce several cytokines, particularly pro-inflammatory ones such as IL-6, tumor necrosis factor (TNF)-α, and IL-1β. Targeting inflammatory pathways are of great interest in stroke research. In this study, we investigated the role of IL-32γ in a middle cerebral artery occlusion (MCAO) model using transgenic (TG) mice expressing human IL-32γ. Compared to wild-type (WT) mice, IL-32γ TG mice exhibited a significantly reduced infarct volume after MCAO. Accompanying the decreased brain tissue damage, the levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β were markedly lower in IL-32γ TG mice than in WT controls. These findings suggest that IL-32γ attenuates the inflammatory response in ischemic brain injury. Specifically, IL-32γ reduced the expression of pro-inflammatory cytokines and the number of apoptotic cells following ischemic insult. In conclusion, our results demonstrate that IL-32γ protects the neuroinflammatory response in brain injury and may serve as a potential neuroprotective therapeutic target.

Keywords

stroke / IL-32γ / proinflammatory cytokine / IL-32γ TG / middle cerebral artery occlusion

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