Neuroprotective effects of platinum nanoparticle-based microreactors in a pilocarpine-induced rat model of epilepsy

Epilepsy is a neurological disorder characterized by recurrent seizures resulting from excessive and synchronous electrical activity in the brain. Hyperexcitability leads to increased intracellular calcium, oxidative stress, and neuronal damage, promoting neurodegeneration and long-term reorganization of brain circuits. Approximately 30% of individuals diagnosed with epilepsy do not respond adequately to currently available pharmacological treatments, underscoring the need for alternative therapeutic strategies. Previous studies demonstrated that platinum nanoparticle (Pt-NP)-based microreactors can counteract excitotoxicity and associated oxidative stress in primary neuronal cultures, as well as attenuate both behavioral and neurobiological alterations accompanying bicuculline-induced seizures in a rat model. The present study aimed to further investigate in vivo the neuroprotective effects of these microreactors in a Status Epilepticus (SE) model induced by intrahippocampal administration of pilocarpine. Male Wistar rats received a preventive treatment (microinjection of microreactors) followed, seven days later, by seizure induction (microinjection of pilocarpine). Seizure activity was monitored for 120 min. Behavioral assessments were conducted between days 11-15 post-induction using the elevated plus maze, open field, novel object recognition, and splash tests. Subsequently, brain tissue was processed to evaluate inflammation, neurogenesis, neurodegeneration, and oxidative stress. Treatment with the microreactors reduced seizure susceptibility and prevented motor impairments and depressive-like behavior. Immunohistochemical and oxidative stress analyses further confirmed their neuroprotective and anti-inflammatory profile. Overall, these findings suggest that Pt-NP-based microreactors could reduce seizure risk, as well as prevent pilocarpine-induced behavioral and molecular impairments, highlighting their potential as a candidate for the development of next-generation therapies to prevent epileptogenesis and related comorbidities. SYNOPSIS: Astrocyte-inspired Pt-NP-based microreactors function as artificial cells to locally modulate the brain's biochemical microenvironment. By scavenging neurotoxic by-products, treatment with these microreactors prevents pilocarpine-induced behavioral alterations. The technology also averts pilocarpine-induced neuroinflammation, cell death, increased neurogenesis, and exacerbated oxidative stress, potentially representing a novel therapeutic approach to prevent epileptogenesis.