Brain research bulletin · 2026
Needle-knife attenuates excessive autophagy and ferroptosis in post-stroke spastic hemiplegia: Association with SDC1/NRF2/SLC7A11/GPX4 pathway.
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Wang Yinyu, Zhou Qingyan, Yang Shuo, Liu Minghui
Аннотация
OBJECTIVE: The aim of this study is to explore the molecular mechanism of needle-knife in inhibiting ferroptosis and excessive activation of autophagy, reducing nerve injury and improving motor function in post-stroke spastic hemiplegia (PSSH) rats.
METHODS: A rat model of PSSH was established using middle cerebral artery occlusion (MCAO). Neurological function and motor performance were evaluated using modified Ashworth Scale (mASS), Modified Ashworth Scale (MAS) and balance beam test. TTC staining, Nissl staining and transmission electron microscopy were used to detect the cerebral infarction area and neuronal injury. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), glutathione (GSH) and ferrous ion (Fe²⁺) were measured by ELISA. Protein expressions of SDC1, nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), GPX4 and autophagy-related proteins (LC3, p62, Beclin1) were determined by immunohistochemistry (IHC) or Western blotting (WB).
RESULTS: Compared with the sham group, the cerebral infarction area of rats in MCAO and Erastin groups increased, the neuronal damage was obvious and the mitochondrial structure was disordered. The levels of ROS, MDA and Fe²⁺ in the infarct area were significantly increased (P < 0.05), and the levels of GSH and GPX4 were decreased (P < 0.05). At the same time, the expressions of SDC1, NRF2, SLC7A11 and GPX4 in the infarction area were decreased (P < 0.05), the autophagy-related proteins LC3II/I and Beclin1 were increased (P < 0.05), and P62 was decreased (P < 0.05). Compared with the MCAO group, the needle knife treatment could improve the nerve damage in PSSH rats, restore their motor functions, and rescue the aforementioned molecular levels (P < 0.05). Compared with the needle knife group, the ferroptosis activator (Erastin), NRF2 inhibitor (ML385), and autophagy activator (rapamycin) significantly reversed the therapeutic effect of the needle knife (P < 0.05).
CONCLUSIONS: Needle-knife alleviates ferroptosis and inhibits excessive autophagy in PSSH rats, and the underlying mechanism may be potentially related to the upregulation of SDC1 and the NRF2/SLC7A11/GPX4 pathway.
METHODS: A rat model of PSSH was established using middle cerebral artery occlusion (MCAO). Neurological function and motor performance were evaluated using modified Ashworth Scale (mASS), Modified Ashworth Scale (MAS) and balance beam test. TTC staining, Nissl staining and transmission electron microscopy were used to detect the cerebral infarction area and neuronal injury. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), glutathione (GSH) and ferrous ion (Fe²⁺) were measured by ELISA. Protein expressions of SDC1, nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), GPX4 and autophagy-related proteins (LC3, p62, Beclin1) were determined by immunohistochemistry (IHC) or Western blotting (WB).
RESULTS: Compared with the sham group, the cerebral infarction area of rats in MCAO and Erastin groups increased, the neuronal damage was obvious and the mitochondrial structure was disordered. The levels of ROS, MDA and Fe²⁺ in the infarct area were significantly increased (P < 0.05), and the levels of GSH and GPX4 were decreased (P < 0.05). At the same time, the expressions of SDC1, NRF2, SLC7A11 and GPX4 in the infarction area were decreased (P < 0.05), the autophagy-related proteins LC3II/I and Beclin1 were increased (P < 0.05), and P62 was decreased (P < 0.05). Compared with the MCAO group, the needle knife treatment could improve the nerve damage in PSSH rats, restore their motor functions, and rescue the aforementioned molecular levels (P < 0.05). Compared with the needle knife group, the ferroptosis activator (Erastin), NRF2 inhibitor (ML385), and autophagy activator (rapamycin) significantly reversed the therapeutic effect of the needle knife (P < 0.05).
CONCLUSIONS: Needle-knife alleviates ferroptosis and inhibits excessive autophagy in PSSH rats, and the underlying mechanism may be potentially related to the upregulation of SDC1 and the NRF2/SLC7A11/GPX4 pathway.