Impact Of Polycaprolactone/Carbon Nanotube Scaffold Enriched With Liposomal Ellagic Acid On Hippocampal Synaptogenesis Following Spinal Cord Injury

Objective(s): Impairments in memory and cognition are significant secondary effects of spinal cord injury (SCI) affecting the hippocampus. This study aimed to investigate the impact of implanting a polycaprolactone/functionalized multiwall carbon nanotube (PCL/f-MWCNT) scaffold combined with ellagic acid-loaded liposomes (EA@lip) on neurological recovery and hippocampal deficits following SCI.Methods: Twenty-four female Wistar rats were randomly divided into four groups (n=۶): Ctrl- group (laminectomy without SCI), Ctrl+ group (SCI), PCL/CNT group (implantation of PCL/f-MWCNT scaffold), and PCL/CNT/EA group (implantation of PCL/f-MWCNT/EA@lip scaffold). The injury model involved dorsal hemisection at the T۹ level. Characterization of EA@lip, achieved through a remote loading method, was performed using transmission electron microscopy and dynamic light scattering. Additionally, the morphology of PCL/f-MWCNT fibers was examined via field-emission scanning electron microscopy (FE-SEM). Behavioral assessments were conducted to evaluate the neurobehavioral performance of the animals. After four weeks, excitatory postsynaptic potentials were recorded from the CA۱ region of the hippocampus. The mRNA levels of amyloid beta precursor protein (APP), cyclic nucleotide phosphodiesterase (CNP), glutamate ionotropic receptor kainate type subunit ۲ (GRIK۲), and syntaxin-binding protein ۱ (Munc ۱۸-۱) in the hippocampus were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results: The results indicated that the implantation of the PCL/CNT scaffold, with or without EA@lip, enhanced hippocampal action potentials, as evidenced by increased slope and amplitude of fEPSP compared to the Ctrl+ group. RT-qPCR analysis revealed that CNP and Munc ۱۸-۱ expression levels were elevated, while APP and GRIK۲ expression levels decreased in the groups receiving PCL/CNT with or without EA@lip, relative to the injury group. Furthermore, treatment with PCL/CNT/EA@lip significantly improved behavioral performance compared to the Ctrl+ and PCL/CNT groups.Conclusion: This study demonstrated that the implantation of the PCL/f-MWCNT/EA@lip scaffold enhances functional recovery and modifies the expression of memory-related genes in the hippocampus following injury

کلیدواژه ها:

Action potentials ، Drug delivery systems ، Tissue engineering ، Memory ، Neurogenesis.