David Loane, PhD, is an Assistant Professor of Anesthesiology and Faculty Member at the Center for Shock, Trauma and Anesthesiology Research (STAR) at the University of Maryland School of Medicine, Baltimore, Maryland. Dr. Loane conducted his graduate studies at the Department of Pharmacology and MRC Center for Synaptic Plasticity, University of Bristol, England, and obtained his PhD in Neuroscience in 2005. He then pursued postdoctoral training with Dr. Marina Lynch at Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland, where he studied neuroinflammatory changes in the aged and Alzheimer's disease (AD) brain. In 2007 Dr. Loane was recruited to the Department of Neuroscience, Georgetown University Medical Center, Washington D.C., to perform further postdoctoral training on experimental models of traumatic brain injury (TBI) under the mentorship of Dr. Alan Faden. He joined the faculty of the University of Maryland School of Medicine in November 2009 and is currently Assistant Professor of Anesthesiology.
Dr. Loane's research program is focused on understanding common secondary injury pathways that link acute brain injury mechanisms with age-associated chronic neurodegenerative diseases such as AD. Neuroinflammation is a key secondary injury mechanism that contributes to chronic neurodegeneration and loss of neurological function after TBI. In response to CNS injury microglia become activated and acquire one of two functionally distinct activation phenotypes. In the "classical activation" or M1 state, microglia, in an effort to remove injured tissue or achieve pathogen destruction release pro-inflammatory cytokines and activate NADPH oxidase generating reactive oxygen species. However, excessive M1 transformation can lead to exacerbation of injury and progressive tissue destruction. In contrast, other microglia show an alternative ("alternative activation") phenotype or M2 state, which serves to dampen the inflammatory response and promote tissue repair and plasticity responses. Whether microglia differentiate into an M1 phenotype that contributes to secondary injury or into an M2 phenotype that promotes repair likely depends on the signals within the lesion microenvironment as well as systemic factors. Little is known about the relative effects and timing of M1 and M2 microglial activation phenotypes after TBI, or how aging may influence this balance. The goal of Dr. Loane's research is to examine the role of microglial activation phenotypes in response to TBI, and to develop novel therapeutic strategies to modulate microglial form and function in the acute and chronic periods of recovery after TBI.
Selected peer-review articles
Loane DJ, Pocivavsek A, Moussa CE-H, Thompson R, Matsuoka Y, Faden AI, Rebeck GW, Burns MP. APP secretases as therapeutic targets for traumatic brain injury. Nature Medicine. 2009 15 377-9. PMID 19287391.
Loane DJ, Deighan BF, Clarke RM, Griffin RJ, Lynch AM, Lynch MA. Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain. Neurobiology of Aging. 2009 30 920-31. PMID 17950491.
Loane DJ, Stoica BA, Pajoohesh-Ganji A, Byrnes KR, Faden AI. Activation of metabotropic glutamate receptor 5 (mGluR5) modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase. Journal of Biological Chemistry. 2009 284 15629-15639. PMID 19634772.
Loane DJ, Washington PM, Vardanian L, Pocivavsek A, Hoe HS, Duff KE, Cernak I, Rebeck GW, Faden AI, Burns MP. Modulation of ABCA1 by an LXR agonist reduces beta-amyloid levels and improves outcome after traumatic brain injury. Journal of Neurotrauma. 2011 28(2): 225-36. PMID 21975399.
Kabadi SV, Stoica BA, Byrnes KR, Hanscom M, Loane DJ, Faden AI. Selective CDK inhibitor limits neuroinflammation and progressive neurodegeneration after brain trauma. Journal of Cerebral Blood Flow and Metabolism. 2012 32(1):137-49. PMID 21829212.
Kabadi SV, Stoica BA, Loane DJ, Byrnes KR, Hanscom M, Cabatbat RM, Tan MT, Faden AI. Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury. Journal of Neurotrauma. 2012 29(5):813-27. PMID 21895533.
Kabadi SV, Stoica BA, Hanscom M, Loane DJ, Kharebava G, Murray MG II, Cabatbat RM, Faden AI. CR8, a Selective and Potent CDK Inhibitor, Provides Neuroprotection in Experimental Traumatic Brain Injury. Neurotherapeutics. 2012 9(2):405-21. PMID 22167461.
Byrnes KR*, Loane DJ*, Stoica BA, Zhang Z, Faden AI. Delayed mGluR5 activation reduces chronic inflammation and neurodegeneration after brain trauma. Journal of Neuroinflammation. 2012 9:43. (*co-first author) PMID 22426396.
Zhao Z, Loane DJ, Murray MG 2nd, Stoica BA, Faden AI. Comparing the predictive value of multiple cognitive, affective, and motor tasks after rodent traumatic brain injury. Journal of Neurotrauma. 2012 29(15):2475-89. PMID: 22924665.
Piao CS, Loane DJ, Stoica BA, Li S, Hanscom M, Cabatbat RM, Blomgren K, Faden AI. Combined inhibition of cell death induced by apoptosis inducing factor and caspases provides additive neuroprotection in experimental traumatic brain injury. Neurobiology of Disease. 2012 46(3):745-58. PMID 22426396.
Loane DJ, Stoica BA, Byrnes K, Jeong W, Faden AI. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. Journal of Neurotrauma. 2012 Nov 30. [Epub ahead of print] PMID: 23199080.
Kumar A, Stoica BA, Sabirzhanov B, Burns MP, Faden AI, Loane DJ. Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states. Neurobiology of Aging. 2012 Dec 27 [Epub ahead of print]. PMID: 23273602.
Reviews, commentaries and book chapters
Byrnes KR, Loane DJ, Faden AI. Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders. Neurotherapeutics. 2009 6(1):94-107. PMID: 19110202.
Loane DJ, Byrnes KR. Role of microglia in neurotrauma. Neurotherapeutics. 2010 7(4):366-77. PMID: 20880501.
Loane DJ, Faden AI. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends in Pharmacological Sciences. 2010 31(12):596-604. PMID: 21035878.
Loane DJ, Stoica BA, Faden AI. Metabotropic glutamate receptor-mediated signaling in neuroglia. Wiley Interdisciplinary Reviews Membrane Transport and Signaling. 2012 1(2):136-150. PMID: 22662309.
Kumar A, Loane DJ. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behavior and Immunity. 2012 26(8):1191-201. PMID: 22728326.
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