Intravenous Immunoglobulin Treatment Preserves and Protects Primary Rat Hippocampal Neurons and Primary Human Brain Cultures Against Oxidative Insults

Author(s): Debomoy K. Lahiri, Balmiki Ray

Journal Name: Current Alzheimer Research

Volume 11 , Issue 7 , 2014

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Alzheimer’s disease (AD) is characterized by deleterious accumulation of amyloid-β (Aβ) peptide into senile plaque, neurofibrillary tangles formed from hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral cortex. The deposition of Aβ-loaded plaques results in microglial activation and subsequent production of reactive oxygen species (ROS), including free radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons against ROS may provide therapeutic values for the treatment or prevention of AD. In the present study, our goal was to test whether intravenous immunoglobulin (IVIG) treatment could preserve as well as protect neurons from oxidative damage. We report that treatment with IVIG protects neuronal viability and synaptic proteins in primary rat hippocampal neurons. Further, we demonstrate the tolerability of IVIG treatment in the primary human fetal mixed brain cultures. Indeed, a high dose (20mg/ml) of IVIG treatment was well-tolerated by primary human brain cultures that exhibit a normal neuronal phenotype. We also observed a potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in these human fetal brain cultures. These results indicate that IVIG treatment has great potential to preserve and protect primary human neuronal-enriched cultures and to potentially rescue dying neurons from oxidative insults. Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology.

Keywords: Aging, brain, hippocampal neuron, human neuron, immunoglobulin, neuroprotection, neuropreservation, neurorescue, oxidative stress, synapse, synaptic protein.

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Article Details

Year: 2014
Published on: 11 August, 2014
Page: [645 - 654]
Pages: 10
DOI: 10.2174/1567205011666140812113851
Price: $65

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