TY - JOUR
T1 - Neuronal HIF-1α protein and VEGFR-2 immunoreactivity in functionally related motor areas following a focal M1 infarct
AU - Stowe, Ann M.
AU - Plautz, Erik J.
AU - Nguyen, Phuong
AU - Frost, Shawn B.
AU - Eisner-Janowicz, Ines
AU - Barbay, Scott
AU - Dancause, Numa
AU - Sensarma, Anirban
AU - Taylor, Michael D.
AU - Zoubina, Elena V.
AU - Nudo, Randolph J.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - HIF-1α (hypoxia inducible factor-1α)
KW - Neuron
KW - Stereology
KW - Stroke
KW - VEGF (vascular endothelial growth factor)
KW - VEGF receptor-2 (VEGFR-2)
UR - http://www.scopus.com/inward/record.url?scp=39749199403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39749199403&partnerID=8YFLogxK
U2 - 10.1038/sj.jcbfm.9600560
DO - 10.1038/sj.jcbfm.9600560
M3 - Article
C2 - 17895908
AN - SCOPUS:39749199403
SN - 0271-678X
VL - 28
SP - 612
EP - 620
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 3
ER -