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Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways.


ABSTRACT: Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimer's disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell death in experimental models of stroke and Alzheimer's disease. Treatment of cultured neurons with IVIg reduced simulated ischemia- and amyloid ?peptide (A?)-induced caspase 3 cleavage, and phosphorylation of the cell death-associated kinases p38MAPK, c-Jun NH2 -terminal kinase and p65, in vitro. Additionally, A?-induced accumulation of the lipid peroxidation product 4-hydroxynonenal was attenuated in neurons treated with IVIg. IVIg treatment also up-regulated the anti-apoptotic protein, Bcl2 in cortical neurons under ischemia-like conditions and exposure to A?. Treatment of mice with IVIg reduced neuronal cell loss, apoptosis and infarct size, and improved functional outcome in a model of focal ischemic stroke. Together, these results indicate that IVIg acts directly on neurons to protect them against ischemic stroke and A?-induced neuronal apoptosis by inhibiting cell death pathways and by elevating levels of the anti-apoptotic protein Bcl2.

SUBMITTER: Widiapradja A 

PROVIDER: S-EPMC5146755 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Intravenous immunoglobulin protects neurons against amyloid beta-peptide toxicity and ischemic stroke by attenuating multiple cell death pathways.

Widiapradja Alexander A   Vegh Viktor V   Lok Ker Zhing KZ   Manzanero Silvia S   Thundyil John J   Gelderblom Mathias M   Cheng Yi-Lin YL   Pavlovski Dale D   Tang Sung-Chun SC   Jo Dong-Gyu DG   Magnus Tim T   Chan Sic L SL   Sobey Christopher G CG   Reutens David D   Basta Milan M   Mattson Mark P MP   Arumugam Thiruma V TV  

Journal of neurochemistry 20120427 2


Intravenous immunoglobulin (IVIg) preparations obtained by fractionating blood plasma, are increasingly being used increasingly as an effective therapeutic agent in treatment of several inflammatory diseases. Its use as a potential therapeutic agent for treatment of stroke and Alzheimer's disease has been proposed, but little is known about the neuroprotective mechanisms of IVIg. In this study, we investigated the effect of IVIg on downstream signaling pathways that are involved in neuronal cell  ...[more]

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