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Background and purpose: Spinal cord injury (SCI) causes motor and cognitive impairments, with secondary hippocampal damage contributing to memory deficits. This study examined the effects of neural stem cell (NSC)-laden polyurethane/functionalized multiwalled carbon nanotube (PU/f-MWCNT) scaffolds coated with liposomal hesperidin (Hsd@lip) on hippocampal synaptic integrity, neuroinflammation, and memory in a rat model of dorsal hemisection SCI. Experimental approach: Electrospun PU/f-MWCNT scaffolds were prepared and loaded with NSCs, Hsd@lip, or both. Wistar rats (n = 15/group) were assigned to untreated SCI, scaffold+Hsd@lip (PCH), scaffold+NSC (PCN), or scaffold+NSC+Hsd@lip (PCHN). Four weeks post-implantation, hippocampal synaptic plasticity, oxidative stress, neuronal survival, and memory performance were evaluated using electrophysiology, biochemical assays, histology, and behavioral tests. Findings/Results: The scaffolds were uniform, bead-free fibers with an average diameter of 174.7 ± 63.5 nm. Hsd@lip coating formed a thin, non-aggregated layer that maintained scaffold porosity. Cell seeding demonstrated good NSC adhesion and spreading, supporting the scaffold's biocompatibility. Compared to the SCI group, animals treated with PCHN exhibited a significant reduction in MDA levels and decreased AChE activity, and increased thiol content. Doublecortin expression markedly increased, while NF-κB levels and dark neuron counts significantly reduced. Furthermore, cognitive function improved. Conclusion and implications: These findings highlight the potential of NSC-laden PU/f-MWCNT scaffolds coated with Hsd@lip to mitigate hippocampal damage, restore synaptic integrity, and improve cognitive function following SCI. This multimodal approach offers a promising therapeutic strategy for addressing the cognitive sequelae of SCI.
Rad et al. (Mon,) studied this question.