Intrathecal Administration of [Pyr1] apelin-13 Improves Functional Recovery in Rat Via Reducing Astrocytic Induced Inflammation in Ventral and Dorsal Spinal Cord
摘要
Astrocytes play a critical role in secondary neuroinflammation following spinal cord injury (SCI). Apelin, an endogenous neuroprotective peptide and ligand of the APJ receptor, has demonstrated anti-inflammatory effects in both the central and peripheral nervous systems. This study aimed to evaluate the effects of [Pyr1] apelin-13 on astrocyte-mediated inflammation in a rat model of SCI.
Materials and methodsAdult rats were randomly divided into 6 groups: intact, sham, SCI, SCI + vehicle (normal saline, 10 µL, intrathecally), and SCI+[Pyr1] apelin-13 (1 µg in 10 µl of normal saline) and SCI+[Pyr1] apelin-13 (5 µg in 10 µl of normal saline). SCI was induced using the clip-compression method. [Pyr1] apelin-13 or vehicle was administered intrathecally once daily for seven consecutive days, beginning on day 1 post-injury. Locomotor function was assessed over an 8-week period using the BBB scoring method. At the end of the study, spinal cord tissues were harvested for analysis of glial fibrillary acidic protein (GFAP) expression via immunohistochemistry and IL-10 levels via Western blot.
ResultsSCI significantly impaired locomotor function, upregulated GFAP expression, and downregulated IL-10 levels. Intrathecal administration of [Pyr1] apelin-13 (1 µg and 5 µg) significantly improved locomotor recovery, reduced GFAP expression, and increased IL-10 levels, with the 5 µg dose showing greater efficacy.
ConclusionThese findings suggest that [Pyr1] apelin-13 has anti-inflammatory and neuroprotective effects in SCI, likely through modulation of astrocytic activity and upregulation of IL-10. This peptide may represent a promising therapeutic agent for reducing neuroinflammation and improving functional outcomes following SCI.