The intravenous targeted nanopeptide, CAQK, is neuroprotective and improves motor function after spinal cord injury in rats

BACKGROUND: CAQK is a homing peptide that targets sites of central nervous system injury and has previously demonstrated functional benefits in traumatic brain injury models. We recently demonstrated its localization to spinal cord injury (SCI) after intravenous administration and hypothesized that it could enhance motor recovery after SCI. METHODS: Twelve female Sprague-Dawley rats underwent C5 right-sided spinal cord hemicontusion. Animals were randomized to receive intravenous CAQK (2.5 mg/kg) or saline daily for 7 days, beginning 1 hour postinjury. Motor performance was assessed using the Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale, a scale from 0 to 9, with 9 being normal function. IBB score was assessed at five time points over 8 weeks, followed by histological analysis. An in vitro neuroprotection assay was also conducted to evaluate the neuroprotective effects of CAQK at various doses. RESULTS: All animals exhibited motor deficits immediately after injury. Compared with saline controls, CAQK-treated rats demonstrated significantly improved motor recovery at 1, 2, 5, and 8 weeks postinjury (week 8: IBB = 7 vs. 3; p = 0.01). Histologic analysis showed significantly reduced astroglial activation in the CAQK group (GFAP: treated = 0.1±0.01 vs. untreated = 0.7±0.2; p = 0.002) and increased axonal preservation (NFM: treated = 0.3±0.06 vs. untreated = 0.1±0.06; p = 0.03). In vitro, CAQK significantly enhanced neuronal network complexity compared with saline ( p < 0.05). CONCLUSIONS: CAQK treatment significantly improved motor outcomes compared with saline-only treatment. Ex vivo analysis of spinal cord tissue showed enhanced tissue recovery in CAQK-treated rats. In vitro, neuroprotection was evident in cells treated with CAQK. Overall, these findings support CAQK’s potential as a targeted therapeutic candidate for SCI. ( J Trauma Acute Care Surg 2026;00:000–000.