Hippocampal synaptic markers and cognitive recovery in spinal cord injury: the therapeutic potential of neural stem cell-laden carbon nanotube-based fiber scaffolds with liposomal hesperidin

Amirhossein Rabiei Rad , Tahere Mokhtari, Esmael Amirazodi, Amir Mahdi Molavi, Fatemeh Mortazavi Moghadam, Reza Kazemi Oskuee, Arman Abroumand Gholami

Abstract


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.

 

 


Keywords


Action potentials; Drug delivery systems; Memory; Neurogenesis; Stem cell therapy; Tissue engineering.

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References


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