Early inhibition of TNFα increases 6-hydroxydopamine-induced striatal degeneration

Carmelina Gemma, Briony Catlow, Michael Cole, Charles Hudson, Amy Samec, Nishan Shah, Jennifer Vila, Adam Bachstetter, Paula C. Bickford

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Evidence suggests that tumor necrosis factor alpha (TNF) is a leading cause of dopaminergic neuronal cell death. TNF also, however, has neuroprotective effects. Thus, TNF might have a dual role following injury: immediate release after injury is protective, whereas chronic increases are detrimental. In the present study, 6-hydroxydopamine was used to lesion the dorsal striatum in male Fisher 344 rats at 2 different time points. Group 1 received a daily injection of TNFα antisense oligodeoxyribonucleotide (ODN) or control on days 1 through 7 post-lesion. Group 2 received a daily injection of TNF antisense ODN or control on days 5 through 15 post-lesion. Rats were killed on the day following the last injection of TNF antisense ODN. Injection of TNF antisense ODN on days 1 through 7 increased the area of the tyrosine-hydroxylase-negative zone ipsilateral to the injection when compared to controls. In contrast, when inhibition of TNF was delayed, the area of tyrosine hydroxylase loss was significantly reduced. These findings suggest that TNF release is neuroprotective in the early stages of injury but becomes neurotoxic when chronically induced.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalBrain Research
Issue number1
StatePublished - May 25 2007

Bibliographical note

Funding Information:
This work was supported by the Veterans Administration Research Service and Parkinson's Disease Foundation/National Parkinson's Disease joint program.


  • 6-Hydroxydopamine
  • Cytokines
  • Microglia
  • Neuroinflammation
  • Parkinson's disease
  • Tumor necrosis factor

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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