Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury

Tanusree Sen, Nilkantha Sen

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is one of the major cause of morbidity and mortality and it affects more than 1.7 million people in the USA. A couple of regenerative pathways including activation of hypoxia-inducible transcription factor 1 alpha (HIF-1α) are initiated to reduce cellular damage following TBI; however endogenous activation of these pathways is not enough to provide neuroprotection after TBI. Thus we aimed to see whether sustained activation of HIF-1α can provide neuroprotection and neurorepair following TBI. We found that chronic treatment with dimethyloxaloylglycine (DMOG) markedly increases the expression level of HIF-1α and mRNA levels of its downstream proteins such as Vascular endothelial growth factor (VEGF), Phosphoinositide-dependent kinase-1 and 4 (PDK1, PDK4) and Erythropoietin (EPO). Treatment of DMOG activates a major cell survival protein kinase Akt and reduces both cell death and lesion volume following TBI. Moreover, administration of DMOG augments cluster of differentiation 31 (CD31) staining in pericontusional cortex after TBI, which suggests that DMOG stimulates angiogenesis after TBI. Treatment with DMOG also improves both memory and motor functions after TBI. Taken together our results suggest that sustained activation of HIF-1α provides significant neuroprotection following TBI.

Original languageEnglish (US)
Pages (from-to)79-88
Number of pages10
JournalNeuropharmacology
Volume107
DOIs
StatePublished - Aug 1 2016

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Hypoxia-Inducible Factor 1
Transcription Factors
Traumatic Brain Injury
Neuroprotection
1-Phosphatidylinositol 4-Kinase
Erythropoietin
Protein Kinases
Vascular Endothelial Growth Factor A
Cell Survival
Cell Death
Staining and Labeling
Morbidity
Messenger RNA

Keywords

  • Angiogenesis
  • Cell death
  • DMOG
  • HIF-1α
  • Lesion volume
  • Traumatic brain injury

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Treatment with an activator of hypoxia-inducible factor 1, DMOG provides neuroprotection after traumatic brain injury. / Sen, Tanusree; Sen, Nilkantha.

In: Neuropharmacology, Vol. 107, 01.08.2016, p. 79-88.

Research output: Contribution to journalArticle

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