Blood Brain Barrier Integrity

The blood brain barrier (BBB) is well-known for its capacity to limit access of the brain to the circulation. Our BBB research projects are focused on the three main areas. First, we are evaluating the peptide hormone ghrelin and VNS as anti-inflammatory strategies that protect from traumatic brain injury (TBI)-induced neurological deficits and breakdown of the BBB. Second, we are examining Ecrg4 as a mediator of microglia activation and neuroepithelial integrity in glioma and penetrating brain injury. Third, we are characterizing the mechanism and preclinical relevance of vascular normalization using genetic models or pharmacological inhibitors of focal adhesion kinase. In combination, these studies provide a integrated approach for the study of BBB integrity to better understand mechanisms that regulate immune and vascular homeostasis.

Publication Highlights

Lund CV, Nguyen MTN, Owens GC, Pakchoian AJ, Shaterian A, Kruse CA, Eliceiri BP. Reduced glioma infiltration in Src-deficient mice. J Neurooncol 2006 May; 78(1): 19-29. Epub 2006 Mar 22.

Bansal V, Costantini TW, Kroll L, Peterson CY, Loomis WH, Putnam JG, Eliceiri BP, Baird A, Coimbra R. Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis. J Neurotrauma 2009 Aug; 26(8): 1353-9. PMCID: PMC2989839

Gonzalez AM, Berlanga O, Leadbeater WE, Cooper-Charles L, Sims K, Logan A, Eliceiri B, Berry M, Baird A. The deployment of adenovirus-containing gene activated matrices onto severed axons after central nervous system injury leads to transgene expression in target neuronal cell bodies. J Gene Med 2009 Aug; 11(8): 679-88. 

Lee J, Lund-Smith C, Borboa A, Gonzalez AM, Baird A, Eliceiri BP. Glioma-induced remodeling of the neurovascular unit. Brain Res 2009 Sep 8; 1288: 125-34. PMCID: PMC2735571.

Bansal V, Ryu SK, Blow C, Costantini T, Loomis W, Eliceiri BP, Baird A, Wolf P, Coimbra R. The Hormone Ghrelin Prevents Traumatic Brain Injury Induced Intestinal Dysfunction. J Neurotrauma 2010 Dec; 27(12): 2255-60. PMCID: PMC3304249.

Lee J, Borboa A, Chun HB, Baird A, Eliceiri BP. Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma. Cancer Res 2010 Dec 15; 70(24): 10131-40. PMCID: PMC3059220.

Johanson C, Stopa E, Baird A, Sharma H. Traumatic brain injury and recovery mechanisms: peptide modulation of periventricular neurogenic regions by the choroid plexus-CSF nexus. J Neural Transm 2011 Jan; 118(1): 115-33. PMCID: PMC3026679.

Gonzalez AM, Leadbeater WE, Burg M, Sims K, Terasaki T, Johanson CE, Stopa EG, Eliceiri BP, Baird A. Targeting choroid plexus epithelia and ventricular ependyma for drug delivery to the central nervous system. BMC Neurosci 2011 Jan 7; 12: 4. PMCID: PMC3025905

Lee J, Borboa AK, Baird A, Eliceiri BP. Non-invasive quantification of brain tumor-induced astrogliosis. BMC Neurosci 2011 Jan 19; 12(1): 9. PMCID: PMC3033849.

Podvin S, Gonzalez AM, Miller MC, Dang X, Botfield H, Donahue JE, Kurabi A, Boissaud-Cooke M, Rossi R, Leadbeater WE, Johanson CE, Coimbra R, Stopa EG, Eliceiri BP, Baird A. Esophageal cancer related gene-4 is a choroid plexus-derived injury response gene: evidence for a biphasic response in early and late brain injury. PLoS One 2011; 6(9): e24609. PMCID: PMC3173480.

Gonzalez AM, Podvin S, Lin SY, Miller MC, Botfield H, Leadbeater WE, Roberton A, Dang X, Knowling SE, Cardenas-Galindo E, Donahue JE, Stopa EG, Johanson CE, Coimbra R, Eliceiri BP, Baird A. Ecrg4 expression and its product augurin in the choroid plexus: impact on fetal brain development, cerebrospinal fluid homeostasis and neuroprogenitor cell response to CNS injury. Fluids Barriers CNS 2011 Jan 18; 8(1): 6. PMCID PMC3042980.

Lopez N, Krzyzaniak M, Chelsea B, Ortiz-Pomales Y, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Ghrelin prevents disruption of the blood brain barrier after traumatic brain injury. Journal of Neurotrauma 2012 Jan 20; 29(2): 385-93. Epub 2011 Oct 26.

Lopez NE, Krzyzaniak MJ, Costantini TW, Putnam J, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Vagal nerve stimulation decreases blood-brain barrier disruption after traumatic brain injury. J Trauma Acute Care Surg 2012 Jun; 72(6): 1562-6.

Lee J, Baird A, Eliceiri BP. Vascular normalization in cerebral angiogenesis: friend or foe? Methods Mol Biol 2014; 1135: 25-34.