Intravenous Immunoglobulin Protects Neurons Against Amyloid Beta-Peptide Toxicity: In Vitro and Murine Studies

Prompted by interest in its potential use for treatment of stroke and Alzheimer’s disease, a multinational team of investigators exposed cultured neurons with intravenous immunoglobulin (IVIG) to evaluate its effect on downstream signaling pathways involved in neuronal cell death. In vitro treatment of neurons with IVIG reduced both simulated ischemia- and amyloid beta peptide-induced caspase-3 cleavage and phosphorylation of the cell death-associated kinases p38MAPK, JNK and p65.

Additionally, amyloid beta peptide-induced accumulation of the lipid peroxidation product 4-HNE was attenuated in neurons treated with IVIG. IVIG treatment also upregulated the apoptotic protein Bc12 in cortical neurons under a combination of ischemia-like conditions and exposure to amyloid beta.

In a model of focal ischemic stroke, treatment of mice with IVIG was shown to reduce neuronal cell loss, apoptosis and infarct size, and improved functional outcome. Together, these results indicate that IVIG acts directly on neurons to protect them against ischemic stroke and amyloid beta-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bc12, the authors concluded.