Glial-derived Neuroinflammation induced with Amyloid-beta-peptide Plus Fibrinogen Injection in Rat Hippocampus

Abstract

Introduction: The present study has examined microglial and astrocyte activation in association with neuronal degeneration in an animal model using an injection of amyloid-beta peptide Aβ1-42 (Aβ42) plus fibrinogen into rat hippocampus. Methods: The combination of stimuli is suggested as a novel and potent perturbation to induce gliosis and the production of glial-derived neurotoxic factors in an animal model exhibiting a leaky BBB (blood-brain barrier). Specifically, Aβ42+fibrinogen stimulation elevated levels of COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) with a considerable extent of neuronal loss associated with microglia and astrocyte activation. Results: Treatment of injected rats with the broad spectrum anti-inflammatory agent, minocycline or the iNOS inhibitor, 1400W inhibited gliosis, reduced levels of COX-2 and iNOS, and demonstrated efficacy for neuroprotection. Conclusion: The findings suggest the utility of combining peptide plus fibrinogen as a potent and understudied neuroinflammatory stimulus for the induction of glial-derived neurotoxic factors in BBB-compromised AD brain.