TGN-020 ameliorates motor dysfunction post-spinal cord injury via enhancing astrocyte autophagy and mitigating inflammation by activating AQP4/PPAR-γ/mTOR pathway.

Spinal Cord Injury (SCI) is a severe condition that often leads to substantial neurological impairments. This study aimed to explore the role of Aquaporin-4 (AQP4) in regulating astrocyte autophagy and neuroinflammation post-SCI, as well as to evaluate the therapeutic potential of AQP4 inhibition using the specific inhibitor TGN-020. Using Western blot, CCK8 assays, immunofluorescence staining, histopathological assessments, and behavioral analyses, we investigated the effects of TGN-020 on SCI-induced alterations in autophagy, neuroinflammation, astrocyte proliferation, neuronal damage, and motor function recovery in both rat and astrocyte models.

miR‑222-3p reduces neuronal cell apoptosis and alleviates spinal cord injury by inhibiting Bbc3 and Bim.

Spinal cord injury (SCI) is a severe traumatic event, but without any established effective treatment because of the irreversible neuronal death. Here, we investigated the role of miR-222-3p in neuronal apoptosis following SCI. Rat SCI models and neuron hypoxia models were accordingly established.

Upregulation of TRPC6 inhibits astrocyte activation and proliferation after spinal cord injury in rats by suppressing AQP4 expression.

Aims: This work investigates the effects and mechanisms of inhibiting TRPC6 (a non-selective cation channel) downregulation on rat astrocyte activation and proliferation following spinal cord injury (SCI) by suppressing AQP4 expression. We used HYP9 (TRPC6-specific agonist) and TGN-020 (AQP4-specific inhibitor) to explore the relationship between TRPC6 and AQP4 and their probable protective effects on SCI.

Methods: In a rat SCI model, we randomly assigned female Sprague-Dawley rats into the following four groups: Sham, SCI, SCI+HYP9, and SCI+TGN-020.

Inhibition of ERK1/2 phosphorylation attenuates spinal cord injury induced astrocyte activation and inflammation through negatively regulating aquaporin-4 in rats.

The extracellular signal-regulated kinase (ERK) pathway has been reported to play a pivotal role in mediating spinal cord injury (SCI) progression. The present study aimed to investigate the effects of phosphorylated ERK1/2 (p-ERK1/2) inhibition on SCI-induced astrocyte activation and inflammation and its possible mechanism in rats. Here, female Sprague-Dawley rats were randomly assigned to four groups: (1) Sham group, (2) SCI group, (3) TGN-020 group (aquaporin-4, AQP4, blocking agent), (4) PD98059 group (ERK blocking agent).