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Soluble Glycoprotein 130Fc Reduces Controlled Cortical Impact-Induced Cognitive Deficits in Rats

Year: 2025

Type: article

Abstract: Traumatic brain injury (TBI) can lead to cognitive dysfunction, with underlying mechanisms poorly understood. Interleukin (IL)-6, particularly via soluble IL-6 receptor (sIL-6R) trans-signaling, can exacerbate neurodegeneration. Soluble glycoprotein (sgp)130 inhibits this pathway, reducing neuroinflammation and improving cognition in a mouse TBI model. In this study, we evaluated sgp130Fc on cognitive recovery and neural damage using a severe controlled cortical impact (CCI) injury model in rats. Male rats ( N = 37) underwent CCI (6-mm flat-tip impactor; 4.0 m/sec; 2.8 mm deformation) or sham procedures and received sgp130Fc (10 mg/kg) or vehicle (VEH) intraperitoneally every 3 days starting 1 day post-injury (dpi). Motor function (beam walk and balance; 1–7 dpi), and spatial learning and memory (Morris water maze [MWM], 14–19 dpi) were assessed using a repeated measures analysis of variance followed by a Tukey’s post hoc analysis. Lesion volume was assessed (21 dpi) using a two-tailed t -test. CCI rats exhibited transient motor deficits not influenced by sgp130Fc. CCI + VEH rats had longer latencies and path lengths to the submerged platform versus shams ( p < 0.05). On 18 dpi, CCI + sgp130Fc rats had shorter latencies ( p = 0.04) and path lengths ( p = 0.02) versus CCI + VEH rats. CCI + VEH rats displayed more inefficient swim strategies than CCI + sgp130Fc rats. CCI + VEH, but not CCI + sgp130Fc rats, had significantly worse performance on the MWM visible platform trials, particularly with respect to path length, suggesting, along with the swim strategy data, possible benefit with spatial navigation when the platform is utilized as a proximal cue. sgp130Fc did not significantly reduce lesion volume. These findings support sgp130Fc as a potential therapeutic for cognitive recovery following TBI.

Source: Neurotrauma Reports

DOI: 10.1177/2689288x251377032