Neuronal HIF-1α protein and VEGFR-2 immunoreactivity in functionally related motor areas following a focal M1 infarct

Ann M. Stowe, Erik J. Plautz, Phuong Nguyen, Shawn B. Frost, Ines Eisner-Janowicz, Scott Barbay, Numa Dancause, Anirban Sensarma, Michael D. Taylor, Elena V. Zoubina, Randolph J. Nudo

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Clinical and experimental data support a role for the intact cortex in recovery of function after stroke, particularly ipsilesional areas interconnected to the infarct. There is, however, little understanding of molecular events in the intact cortex, as most studies focus on the infarct and peri-infarct regions. This study investigated neuronal immunoreactivity for hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) in remote cortical areas 3 days after a focal ischemic infarct, as both HIF-1α and VEGFR-2 have been implicated in peri-infarct neuroprotection. For this study, intracortical microstimulation techniques defined primary motor (M1) and premotor areas in squirrel monkeys (genus Saimiri). An infarct was induced in the M1 hand representation, and immunohistochemical techniques identified neurons, HIF-1α and VEGFR-2. Stereologic techniques quantified the total neuronal populations and the neurons immunoreactive for HIF-1α or VEGFR-2. The results indicate that HIF-1α upregulation is confined to the infarct and peri-infarct regions. Increases in VEGFR-2 immunoreactivity occurred; however, in two remote regions: the ventral premotor hand representation and the M1 hindlimb representation. Neurons in these representations were previously shown to undergo significant increases in VEGF protein immunoreactivity, and comparison of the two data sets showed a significant correlation between levels of VEGF and VEGFR-2 immunoreactivity. Thus, while remote areas undergo a molecular response to the infarct, we hypothesize that there is a delay in the initiation of the response, which ultimately may increase the 'window of opportunity' for neuroprotective interventions in the intact cortex.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number3
StatePublished - Mar 2008


  • HIF-1α (hypoxia inducible factor-1α)
  • Neuron
  • Stereology
  • Stroke
  • VEGF (vascular endothelial growth factor)
  • VEGF receptor-2 (VEGFR-2)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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