Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway

• Published in: Phytotherapy research 2024-06, Vol.38 (6), p.2669-2686
• Main Authors: Ghaffari, Neda, Mokhtari, Tahmineh, Adabi, Mahdi, Ebrahimi, Babak, Kamali, Morteza, Gholaminejhad, Morteza, Hassanzadeh, Gholamreza
• Format: Article
• Language: English
• Subjects: Animals; Bovine serum albumin; Cell migration; Curcumin; Curcumin - pharmacology; Delayed-Action Preparations - pharmacology; Disease Models, Animal; Gene expression; Glial fibrillary acidic protein; Inflammasomes; Inflammasomes - drug effects; Inflammasomes - metabolism; Inflammation; Male; Nanoparticles; Nanoparticles - chemistry; Nestin; Neural stem cells; Neurogenesis; Neurogenesis - drug effects; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Rats; Rats, Sprague-Dawley; Recovery; Recovery of function; Recovery of Function - drug effects; Regeneration; Regeneration (physiology); Scaffolds; Serum albumin; Serum Albumin, Bovine - chemistry; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - therapy; Stem cells; Tissue engineering; Tissue Scaffolds - chemistry
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.8179

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.