title: VEGF protein associates to neurons in remote regions following cortical infarct.
abstract: Vascular endothelial growth factor (VEGF) is thought to contribute to both neuroprotection and angiogenesis after stroke. While increased expression of VEGF has been demonstrated in animal models after experimental ischemia, these studies have focused almost exclusively on the infarct and peri-infarct regions. The present study investigated the association of VEGF to neurons in remote cortical areas at three days after an infarct in primary motor cortex (M1). Although these remote areas are outside of the direct influence of the ischemic injury, remote plasticity has been implicated in recovery of function. For this study, intracortical microstimulation techniques identified primary and premotor cortical areas in a non-human primate. A focal ischemic infarct was induced in the M1 hand representation, and neurons and VEGF protein were identified using immunohistochemical procedures. Stereological techniques quantitatively assessed neuronal-VEGF association in the infarct and peri-infarct regions, M1 hindlimb, M1 orofacial, and ventral premotor hand representations, as well as non-motor control regions. The results indicate that VEGF protein significantly increased association to neurons in specific remote cortical areas outside of the infarct and peri-infarct regions. The increased association of VEGF to neurons was restricted to cortical areas that are functionally and/or behaviorally related to the area of infarct. There was no significant increase in M1 orofacial region or in non-motor control regions. We hypothesize that enhancement of neuronal VEGF in these functionally related remote cortical areas may be involved in recovery of function after stroke, through either neuroprotection or the induction of remote angiogenesis.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA. astowe@kumc.edu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Stowe
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Plautz
authors.forename: Ines
authors.initials: I
authors.lastname: Eisner-Janowicz
authors.forename: Shawn B
authors.initials: SB
authors.lastname: Frost
authors.forename: Scott
authors.initials: S
authors.lastname: Barbay
authors.forename: Elena V
authors.initials: EV
authors.lastname: Zoubina
authors.forename: Numa
authors.initials: N
authors.lastname: Dancause
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Nudo
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping; D002452:Cell Count; D004558:Electric Stimulation; D007091:Image Processing, Computer-Assisted; D008839:Microelectrodes; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012453:Saimiri; D020521:Stroke / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A