Neuroprotection by Vitamin C Against Ethanol-Induced Neuroinflammation Associated Neurodegeneration in the Developing Rat Brain

CNS Neurol Disord Drug Targets. 2016;15(3):360-70. doi: 10.2174/1871527315666151110130139.


Ethanol induces oxidative stress and its exposure during early developmental age causes neuronal cell death which leads to several neurological disorders. We previously reported that vitamin C can protect against ethanol-induced apoptotic cell death in the developing rat brain. Here, we extended our study to understand the therapeutic efficacy of vitamin C against ethanol-induced oxidative stress, neuroinflammation mediated neurodegeneration in postnatal day 7 (PND7) rat. A single episode of ethanol (5g/kg) subcutaneous administration to postnatal day 7 rat significantly induced the production of reactive oxygen species (ROS), and activated both microglia and astrocytes followed by the induction of different apoptotic markers. On the other hand, due to its free radical scavenging properties, vitamin C treatment significantly reduced the production of reactive oxygen species, suppressed both activated microglia and astrocytes and reversed other changes including elevated level of Bax/Bcl-2 ratio, cytochrome c and different caspases such as caspase-9 and caspase-3 induced by ethanol in developing rat brain. Moreover, vitamin C treatment also reduced ethanol-induced activation of Poly [ADP-Ribose] Polymerase 1(PARP-1) and neurodegeneration as evident from Flouro-Jade-B and Nissl stainined neuronal cell death in PND7 rat brain. These findings suggest that vitamin C mitigated ethanol-induced oxidative stress, neuroinflammation and apoptotic neuronal loss and may be beneficial against ethanol damaging effects in brain development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Ascorbic Acid / pharmacology*
  • Ascorbic Acid / therapeutic use*
  • Brain / drug effects*
  • Brain / growth & development
  • CREB-Binding Protein / metabolism
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Encephalitis / chemically induced
  • Encephalitis / prevention & control*
  • Ethanol / toxicity
  • Fluoresceins / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Neurodegenerative Diseases / chemically induced
  • Neurodegenerative Diseases / prevention & control*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Fluoresceins
  • Glial Fibrillary Acidic Protein
  • Neuroprotective Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • fluoro jade
  • Ethanol
  • CREB-Binding Protein
  • Poly (ADP-Ribose) Polymerase-1
  • Caspase 3
  • Ascorbic Acid