MULTIPLE SCLEROSISPertussis toxin attenuates experimental autoimmune encephalomyelitis by upregulating neuronal vascular endothelial growth factorTang, Zhiweia,c,*; Yin, Jun-Xianga,*; Han, Pengchenga; Gan, Yana; Coons, Stephen W.b; Wang, Chongqianc; Maalouf, Marwana; Shi, JiongaAuthor Information Departments of aNeurology bNeuropathology, St. Joseph’s Hospital and Medical Center, Barrow Neurological Institute, Phoenix, Arizona, USA cDepartment of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China *Zhiwei Tang and Jun-Xiang Yin contributed equally to the writing of this article. Correspondence to Jiong Shi, MD, PhD, Department of Neurology, St. Joseph’s Hospital and Medical Center, Barrow Neurological Institute, 500 W Thomas Road, Phoenix, AZ 85013, USA Tel: +1 602 406 4032; fax: +1 602 798 0899; e-mail: [email protected] Received March 5, 2013 Accepted March 25, 2013 NeuroReport: June 19, 2013 - Volume 24 - Issue 9 - p 469-475 doi: 10.1097/WNR.0b013e3283619fc8 Buy Metrics Abstract We have reported earlier that pertussis toxin (PTx) attenuates the motor deficits in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. PTx protects neurons from inflammatory insults. Vascular endothelial growth factor (VEGF) is also neuroprotective. However, the effect of PTx on VEGF has never been studied. We investigated whether PTx modulates neuronal VEGF expression and how it affects the pathogenesis of EAE. EAE was induced by injecting myelin oligodendrocyte glycoprotein 35–55 peptides with adjuvants into C57BL/6 mice. Clinical scores of EAE were evaluated daily for 19 days. Brain and spinal cord samples were collected and assessed for inflammation and demyelination. VEGF, NeuN for neurons, and Caspase-3 for apoptosis were stained for localization using immunohistochemistry techniques, followed by western blot analysis for quantification. Primary neurons were cultured to assess the direct effect of PTx on neuronal VEGF expression. PTx treatment increases neuronal VEGF expression by up to ∼75% in vitro and ∼60% in vivo, preventing neurons from apoptosis. This leads to resolution in inflammation and remyelination and amendment in motor deficits. Our findings suggest that upregulation of endogenous neuronal VEGF by PTx protects motor deficits in EAE and it is a potential therapeutic option for multiple sclerosis. © 2013 Lippincott Williams & Wilkins, Inc.