TRPC3 Mediates Neurological Dysfunction after Intracerebral Hemorrhage in Mice

Intracerebral hemorrhage (ICH) is a lethal stroke subtype characterized by secondary injury resulting from pathological intracellular Ca²⁺ signaling. Bioactive molecules such as ATP and thrombin activate multiple receptor subtypes. Thus, targeting a common downstream molecular mechanism may be more effective than inhibiting individual receptors. One potential candidate is transient receptor potential canonical 3 (TRPC3), a Ca²⁺-permeable nonselective cation channel activated via Gq/phospholipase C signaling. However, its role in ICH remains unclear. Thus, this study aimed to investigate the role of TRPC3 in neurological dysfunction after ICH by using TRPC3 knockout (KO) mice and astrocyte-specific knockdown approaches. The TRPC3-KO mice exhibited significantly lower neurological deficit scores and performed better on the rotarod test than the wild-type mice at 1 and 3 d after ICH, suggesting that TRPC3 plays a critical role in functional impairment. However, the astrocyte-specific knockdown of TRPC3 using an adeno-associated virus vector did not significantly improve neurological dysfunction. These results indicate that TRPC3 contributes to neurological dysfunction after ICH, but that its pathological role cannot be explained by astrocytic TRPC3 alone, indicating the involvement of multiple cell types. In conclusion, TRPC3 is a key channel involved in neurological dysfunction after ICH, suggesting that targeting TRPC3 may provide a new therapeutic strategy for attenuation of neurological dysfunction after ICH.