Research Projects

(i) Rationale/ gaps in existing knowledge: The CNS's resident macrophages, known as microglia, are tasked with protecting the body against infections. Controlling the pro-inflammatory responses of microglial cells is considered a possible therapeutic approach to reduce aberrant inflammatory responses seen in neurodegenerative diseases because persistent or acute inflammation of microglia causes problems of the central nervous system. Therefore, there is a growing demand to create possible nanostructured anti-inflammatory and anti-oxidative drugs that are biocompatible and have precise delivery. (ii) Novelty: Mannose-mimic nanospheres may enhance neuroprotection and therapeutic results in the central nervous system by imitating the natural mannose binding characteristics. These nanospheres mainly affect active macrophages and microglia by increasing their affinity for CD206 receptors. Protecting against oxidative stress, the synthetic design may improve catalytic and antioxidant qualities. Additionally, the nanospheres improve bioavailability by more precisely targeting microglial cells. Their neuroprotective effects include increasing medication delivery, altering microglial phenotype, and directly scavenging reactive oxygen species, all of which may improve CNS function. (iii) Objectives: 1. To evaluate the biocompatibility, anti-inflammatory and anti-oxidant activity of MNSs loaded with edaravone in the in vitro models 2. To study the decomposition of the lipid membrane on the mannose nanospheres in releasing active components, and to evaluate the neuroprotective efficacy of edaravone by activation of M2 microglia. (iv) Methods: Using hydrothermal synthesis, we create the nanostructures to produce MNSs loaded with edaravone, which, according to the preliminary findings. We postulated that supplementing with edaravone might lessen the inflammatory reactions of activated microglial cells by inhibiting the HMGB1 pathway. BV-2 microglia will be pre-treated with varying doses of edaravone 1 h before LPS stimulation. Griess reagent will be used to measure the expression of nitric oxide (NO), and western blotting will be used to measure the expression of inducible nitric oxide synthase (iNOS). The release of inflammatory cytokines will be assessed using qRT-PCR and ELISA. HMGB1 expression inhibition will be examined by western blotting. (v) Expected outcome: Mannose nanospheres loaded with edaravone have the potential to treat neuroinflammation and microglial activation. They block NF-κB and MAPK signaling pathways, reducing the release of pro-inflammatory mediators. They produce mannose receptors on anti-inflammatory cells, improving microglial cell uptake. The nanospheres' down-regulation of HMGB1 signalling reduces TLR4 and NF-κB pathways, ROS generation, microglial activation, and neuroinflammation. This strategy may provide a targeted and effective way to reduce neuronal damage, manage neuroinflammation, and improve functional recovery.