Intranasal Administration of Chitosan-Nanoparticles Conjugated with Imipramine and its Effect on Stroke-Induced Secondary Neurodegeneration: A Research Protocol

Abstract

Introduction: Stroke is the second leading cause of death and the third leading cause of permanent disability worldwide. Notably, the recovery period post-stroke is crucial as there is a risk of stroke-induced secondary neurodegeneration. Stroke-induced secondary neurodegeneration is the inevitable loss of viable brain tissue at sites distal from the initial infarct. It shares similarities with neurodegenerative diseases and results in neurological deficits, further complicating stroke recovery. Intranasal administration of chitosan-nanoparticles conjugated with imipramine will be tested to determine if they elicit a synergistic effect in mitigating disease processes associated with stroke-induced secondary neurodegeneration. Methods: Treatment and testing will be conducted in 30 male Wistar rats aged 12 months. Stroke will be induced by occluding the middle cerebral artery. Rats will be divided into three groups of 10 and will receive an intranasal dose of either saline (Control, C), 20mg/kg of imipramine (Treatment 1, T1), or 20mg/kg of chitosan-nanoparticles conjugated with imipramine (Treatment 2, T2). Statistical analysis using analysis of variance will determine if chitosan-nanoparticles conjugated with imipramine can mitigate the effects of stroke-induced secondary neurodegeneration determined by the proposed tests. Results: T2 given 20mg/kg of chitosan-nanoparticles conjugated with imipramine is proposed to spend more time exploring the unfamiliar object in the novel object recognition test. Lesser evidence of Alzheimer’s disease in T2 is expected, as measured by the fludeoxyglucose positron emission tomography imaging. A higher serum brain-derived neurotrophic factor measured by an enzyme-linked immunosorbent assay is also expected to be present in T2. Discussion: It is anticipated that chitosan-nanoparticles conjugated with imipramine will exhibit a synergistic effect in mitigating disease processes accompanying stroke-induced secondary neurodegeneration because of properties associated with neuroplasticity and enhanced drug targeting efficacy. Conclusion: This research protocol aims to elucidate a novel treatment that can be applied to stroke recovery to mitigate stroke-induced secondary neurodegeneration, which tends to complicate this crucial period. Our proposal could have implications in the prognosis and management of stroke and post-stroke recovery, respectively, and inspire a framework for the discovery of novel post-stroke therapeutic interventions.