Candice M. Brown, PhD
PO Box 9128
108 Biomedical Road
Morgantown, WV 26506
The long-term research objective of my laboratory is to understand the neuroendocrine and neuroimmune mechanisms that control brain endothelial cell and blood-brain barrier responses to systemic inflammation. My research program addresses how prior acute systemic infections influence stroke severity and accelerate cognitive decline in mouse models of sepsis, ischemic stroke, and Alzheimer’s disease. Our studies will provide insights into how sex differences shape innate inflammatory responses that, in turn, enhance neurological dysfunction and promote neurodegenerative disease.
- Sex differences in brain responses to acute systemic inflammation in sepsis, stroke, and Alzheimer's disease
- Mechanisms that preserve blood-brain barrier integrity and protect cerebral function in brain microvascular endothelial cells
- Brain and peripheral arginine metabolism in stroke and Alzheimer’s disease
Techniques and animal models include
Mouse models of acute and chronic inflammation
- Sepsis - cecal ligation and puncture
- schemic stroke - permanent and transient middle cerebral artery occlusion
- Transgenic models of Alzheimer’s disease and vascular dementias
- Brain endothelial cell primary cultures and hCMEC/D3 cells
- Astrocyte and microglia primary cultures
Histology and microscopy
- Alkaline phosphatase histochemistry and cerebral microvessel analysis
- Fluorescence and confocal microscopy
- LAESI: Laser ablation electrospray ionization
- Nwafor DC, Brichacek AL, Ali A, Brown CM. (2021). Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells. Int J Mol Sci. 22(10):5257.
- Quintana DD, Anantula Y, Garcia JA, Engler-Chiurazzi EB, Sarkar SN, Corbin DR, Brown CM, Simpkins JW. (2021). Microvascular degeneration occurs before plaque onset and progresses with age in 3xTg AD mice. Neurobiol Aging. 105:115-128.
- Kim SJ, Russell AE, Wang W, Gemoets DE, Sarkar SN, Simpkins JW, Brown CM. (2021). miR-146a Dysregulates Energy Metabolism During Neuroinflammation. J Neuroimmune Pharmacol.
- Weil ZM, Karelina K, Whitehead B, Velazquez-Cruz R, Oliverio R, Pinti M, Nwafor DC, Nicholson S, Fitzgerald JA, Hollander J, Brown CM, Zhang N, DeVries AC. (2021). Mild traumatic brain injury increases vulnerability to cerebral ischemia in mice. Exp Neurol. 342:113765.
- Russell AE, Cavendish JZ, Rai A, Vannoy M, Dakhlallah AH, Hu H, Ren X, Amer A, Brown CM, Marsh CB, Simpkins JW, Dakhlallah D. (2021). Intermittent Lipopolysaccharide Exposure Significantly Increases Cortical Infarct Size and Impairs Autophagy. ASN Neuro. 13:1759091421991769.
- Nwafor DC, Chakraborty S, Jun S, Brichacek AL, Dransfeld M, Gemoets DE, Dakhlallah D, Brown CM. (2021). Disruption of metabolic, sleep, and sensorimotor functional outcomes in a female transgenic mouse model of Alzheimer's disease. Behav Brain Res. 398:112983.
- Nwafor DC, Brown CM. (2021). A novel role for tissue-nonspecific alkaline phosphatase at the blood-brain barrier during sepsis. Neural Regen Res. 16(1):99-100.
- Saralkar P, Mdzinarishvili A, Arsiwala TA, Lee YK, Sullivan PG, Pinti MV, Hollander JM, Kelley EE, Ren X, Hu H, Simpkins J, Brown C, Hazlehurst LE, Huber JD, Geldenhuys WJ. (2021). The Mitochondrial mitoNEET Ligand NL-1 Is Protective in a Murine Model of Transient Cerebral Ischemic Stroke. Pharm Res. 38(5):803-817.
- NE Husseini, C Bushnell, CM Brown, D Attix, NS Rost, GP Samsa, CA Colton, LB Goldstein. (2020) Vascular cellular adhesion molecule-1 (VCAM-1) and memory impairment in African-Americans after small vessel-type stroke.J Stroke Cerebrovasc Dis. 29(4):104646.
- DD Quintana, JA Garcia, Y Anantula, SL Rellick, EB Engler-Chiurazzi, SN Sarkar, CM Brown, JW Simpkins. (2020). Amyloid-β causes mitochondrial dysfunction via a Ca2+-driven upregulation of oxidative phosphorylation and superoxide production in cerebrovascular endothelial cells. J Alzheimers Dis. 75(1):119-138.
- DC Nwafor, S Chakraborty, AL Brichacek, S Jun, CA Gambill, W Wang, EB Engler-Chiurazzi, D Dakhlallah, AB Pinkerton, JL Millán, SA Benkovic, CM Brown. (2020). Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis. Brain, behavior, and immunity 84, 115-131
- AL Brichacek, SA Benkovic, S Chakraborty, DC Nwafor, W Wang, S Jun, D Dakhlallah, WJ Geldenhuys, AB Pinkerton, JL Millán, CM Brown. (2019). Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis. Scientific Reports 9 (1), 1-19.
- DA Dakhlallah, J Wisler, M Gencheva, CM Brown, ER Leatherman, K Singh, K Brundage, T Karsies, A Dakhlallah, KW Witwer, CK Sen, TD Eubank, CB Marsh. (2019). Circulating extracellular vesicle content reveals de novo DNA methyltransferase expression as a molecular method to predict septic shock. Journal of Extracellular Vesicles 8 (1), 1669881.
- DD Quintana, SE Lewis, Y Anantula, JA Garcia, SN Sarkar, JZ Cavendish, CM Brown, JW Simpkins. (2019). The cerebral angiome: High resolution MicroCT imaging of the whole brain cerebrovasculature in female and male mice. NeuroImage 202, 116109.
- D Nwafor, C Gambill, A Brichacek, E Engler-Chiurazzi, S Benkovic, CM Brown. (2019). Polymicrobisl infection exacerbates neuroinflamation and worsens Alzheimer's-associated memory loss in a female Alzheimer's Disease transgenic mice model. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 15 (7) P544-P545.
- D Dakhlallah, CM Brown (2019). Sepsis extracellular vesicles as epigenetic mediators of systematic communication in murine: Alzheimer model. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 15 (7), P1035.
- DC Nwafor, AL Brichacek, AS Mohammad, J Griffith, BP Lucke-Wold, SA Benkovic, WJ Geldenhuys, PR Lockman, CM Brown. (2019). Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment. J Cent Nerv Syst Dis 11, 1179573519840652.
- AL Brichacek, CA Gambill, S Kenney, DC Nwafor, H Hu, X Ren, Stanley A Benkovic, CM Brown. (2019). Abstract TP117: Experimental Stroke Induces Chronic Gut Dysbiosis in Male C57BL/6J Mice. Stroke 50 (Suppl_1), ATP117-ATP117.
- Brichacek AL, Brown CM (2018). Alkaline phosphatase: a potential biomarker for stroke and implications for treatment.. Metab Brain Dis.
- Geldenhuys WJ, Benkovic SA, Lin L, Yonutas HM, Crish SD, Sullivan PG, Darvesh AS, Brown CM, Richardson JR. MitoNEET (CISD1) knockout mice show signs of striatal mitochondrial dysfunction and a Parkinson’s Disease phenotype. ACS Chem Neurosci [Epub ahead of print].
- Engler-Chiurazzi EB, Brown CM, Povroznik J, Simpkins JW. Estrogens as neuroprotectants: estrogenic actions in the context of cognitive aging and brain injury. Prog Neurobiol. 2017 Oct; 157: 188-211.
- Hall JL, Ryan JJ, Bray BE, Brown C, Lanfear D, et al. Merging electronic health record data and genomics for cardiovascular research: A science advisory from the American Heart Association. Circ Cardiovasc Genet. 2016 Mar 14; 9(2): 193-202.
- Brown CM, Bushnell CD, Samsa G, Goldstein LB, Colton CA. Chronic systemic immune dysfunction in African-Americans with small vessel-type ischemic stroke. (2015) Transl Stroke Res. 6: 430-436.
- Kan MJ, Lee JE, Wilson JG, Everhart AL, Brown CM, Hoofnagle AN, Jansen M, Vitek MP, Gunn MD, Colton CA. Arginine deprivation and immune suppression in a mouse model of Alzheimer's disease. (2015) J Neurosci. 35: 5969-5982.
- Vachharajani V, Liu TF, Brown CM, Wang X, Buehler N, Wells JD, Yoza BK, McCall CM. SIRT1 inhibition during hypoinflammatory phenotype phase of sepsis enhances immunity and improves outcome. (2014) J Leuk Biol. 96: 785-796.
- Liu TF, Brown CM, El-Gazzar M, McPhail L, Millet P, Rao A, Vachharajani VT, Yoza BK, McCall CE. (2012) Fueling the flame: bioenergy coordinates metabolism and inflammation. J Leuk. Biol. May 9, 2012, epub.
- C.M. Brown, J.O. Becker, P.M. Wise, and A.N. Hoofnagle. (2011). Simultaneous detection of six L-arginine metabolites in human and mouse plasmausing hydrophilic-interaction chromatography and electrospray-tandem mass spectrometry. Clin. Chem. 57:701-709.
- Brown CM, Mulcahey TA, Filipek NC, Wise PM (2010). Production of proinflammatory cytokines and chemokines during neuroinflammation: novel roles for estrogen receptors alpha and beta. Endocrinology 151:4916-4925.