VEGF protein associates to neurons in remote regions following cortical infarct

• Published in: Journal of cerebral blood flow and metabolism 2007-01, Vol.27 (1), p.76-85
• Main Authors: Stowe, Ann M, Plautz, Erik J, Eisner-Janowicz, Ines, Frost, Shawn B, Barbay, Scott, Zoubina, Elena V, Dancause, Numa, Taylor, Michael D, Nudo, Randolph J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain Infarction - metabolism; Brain Infarction - pathology; Brain Mapping; Cardiovascular system; Cell Count; Electric Stimulation; Image Processing, Computer-Assisted; Medical sciences; Microelectrodes; Neurology; Neurons - metabolism; Neurons - pathology; Orthopedic surgery; Pharmacology. Drug treatments; Primates; Saimiri; Stroke - metabolism; Stroke - pathology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Up-Regulation - physiology; Vascular diseases and vascular malformations of the nervous system; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - metabolism; Vasodilator agents. Cerebral vasodilators
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600320

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.