Brown, Craig - University of Victoria - Division of Medical Sciences

个人简介

Dr. Brown's neurobiology lab employs in vivo microscopic imaging technologies such as two-photon microscopy and functional imaging of neuronal and hemodynamic activity that allow the visualization of neuronal structures deep within the living brain or the processing of sensory information in real-time. Focal ischemic stroke leads to a long-lasting increase in vascular permeability in the peri-infarct cortex of young adult and aged mice. 1. Whole-brain image showing Evans blue dye extravasation around the cerebral infarct 3 h after initiating photothrombosis. 2. Representative confocal image showing the halo of Evans blue fluorescence around the cerebral infarct. This halo of diffuse fluorescence usually extends 300–500 micrometers from the infarct border, which we refer to as ‘‘peri-infarct’’ (PI) cortex. Note that cortical areas more distant to the infarct exhibit little to no fluorescence. 3. A toluidine blue stained section showing the infarct core (above right) and peri-infarct region (below right) 72 h after stroke in an aged mouse. The vessels inside the infarct core were either plugged or unrecognizable. Open perfused microvessels were evident in the peri-infarct zone (below right). Close inspection reveals vacuolated endothelium and swollen astrocyte endfeet. 4. Electron microscopic images of capillaries in sham (left), and in the peri-infarct zone of 3 h (middle) and 72 h post-stroke cortical regions. High magnification views of the details of the endothelium reveal intact tight junctions (black arrows) and an increase in vesicles (arrowheads) within the endothelium. Vacuole formation in the endothelium was typical of capillaries in the peri-infarct zone.

研究领域

A central goal of Dr. Brown's research program is to use these experimental approaches to characterize the neurobiological mechanisms that allow the cerebral cortex to develop normally and change throughout life in response to new experiences (eg. learning, drug exposure) or pathology such as stroke or diabetes.

近期论文

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Reeson P, Jeffery A, Brown CE. 2016. Illuminating the effects of stroke on the diabetic brain: Insights from imaging neural and vascular networks in experimental animal models. Diabetes 65:1779-1788. Nahirney, P.C., P. Reeson and C. E. Brown. 2016. Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice. Journal of Cerebral Blood Flow and Metabolism 36(2): 413-25. Reeson P, Tennant KA, Gerrow K, Wang J, Weiser S, Thompson K, Lockhart K.L, Nahirney PC and Brown CE**. 2015. Delayed inhibition of VEGF signaling attenuates blood brain barrier breakdown and improves stroke recovery in a co-morbidity dependent manner. Journal of Neuroscience 35(13):5128-5143. Taylor S, Trudeau D, Arnold B, Wang J, Gerrow K, Summerfeldt K, Holmes A, Zamani A, Brocardo P and Brown CE**. 2015. VEGF can protect against blood barrier dysfunction, dendritic spine loss and spatial memory deficits in an experimental model of diabetes. Neurobiology of Disease 78:1-11. Seto A, Taylor S, Trudeau D, Swan I, Leung J, Reeson P, Delaney KR, Brown CE. 2014. Induction of ischemic stroke in awake freely moving mice reveals that isoflurane anesthesia can mask the benefits of a neuroprotection therapy. Frontiers in Neuroenergetics Apr 3;6:1. Tennant K and Brown CE. 2013. Diabetes augments in vivo microvascular blood flow dynamics after stroke. Journal of Neuroscience 33(49):19194-19204. Sweetnam D and Brown CE. 2013. Stroke induces long-lasting deficits in the temporal fidelity of sensory processing in the somatosensory cortex. Journal of Cerebral Blood Flow and Metabolism 33(1):91-96. Sweetnam D, Holme A, Tennant KA, Zamani A, Walle M, Jone P, Wong C, Brown CE.* 2012. Diabetes impairs cortical plasticity and functional recovery following ischemic stroke. Journal of Neuroscience 32(15):5132-5143. Full text PDF Brown CE, Sweetnam D, Beange M, Nahirnery PC, Nashmi R. 2012. Alpha 4 nicotinic acetylcholine receptors modulate experience-based cortical depression in the adult somatosensory cortex. Journal of Neuroscience 32(4):1207-1219. Full Text PDF Brown CE, Boyd JD and Murphy TH. 2010. Longitudinal in vivo imaging reveals balanced and branch specific dendritic remodeling of mature cortical pyramidal neurons after stroke. Journal of Cerebral Blood Flow and Metabolism 30(4):783-91. Brown CE, Aminoltejari K, Erb H, Winship IR and Murphy TH. 2009. In vivo voltage sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. Journal of Neuroscience 29:1719-1734. Dahlhaus R, Hines RM, Eadie B, Kannangara T, Hines DJ, Brown CE, Christie BR, El-Husseini A. 2009. Over expression of the cell adhesion protein Neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus. Hippocampus 20(2):305-22. Brown CE and Murphy TH. 2008. Livin' on the edge: Imaging dendritic spine turnover in the peri-infarct zone during ischemic stroke and recovery. The Neuroscientist 14:139-146. Brown CE, Wong C and Murphy TH. 2008. Rapid morphological plasticity of peri-infarct dendritic spines after focal ischemic stroke. Stroke 39:1286-1291. Liu RR, Brown CE, Murphy TH. 2007. Differential regulation of cell proliferation in neurogenic zones in mice lacking cystine transport by xCT. Biochemical Biophysical Research Communications 364:528-533. Brown CE, Li P, Boyd JD, Delaney KR and Murphy TH. 2007. Extensive turnover of dendritic spines and vascular remodelling in cortical tissues recovering from stroke. Journal of Neuroscience 27:4101-4109. Flynn C, Brown CE, Galasso SL, McIntyre DC, Teskey GC, Dyck RH. 2007. Zincergic innervation of the forebrain distinguishes epilepsy- prone from epilepsy-resistant rat strains. Neuroscience 144:1409-1414. Brown CE and Dyck RH. 2005. Modulation of synaptic zinc in barrel cortex by whisker stimulation. Neuroscience 134:355-359. Brown CE and Dyck RH. 2005. Retrograde tracing of the subset of afferent connections in mouse barrel cortex provided by zincergic neurons. Journal of Comparative Neurology 486:48-60. Brown CE and Dyck RH. 2004. Distribution of zincergic neurons in the mouse forebrain. Journal of Comparative Neurology 479:156-167. Schuurmans C, Armant O, Nieto M, Stenman JM, Britz O, Klenin N, Seibt J, Brown C, Tang H, Cunningham JM, Dyck R, Walsh C, Campbell K, Polleux F, Guillemot F. 2004. Sequential phases of neocortical fate specification involve Neurogenin-dependent and independent pathways. EMBO Journal 23:2892-2902. Brown CE and Dyck RH. 2003. An improved method for visualizing the cell bodies of zincergic neurons. Journal of Neuroscience Methods 129:41-47. Brown CE and Dyck RH. 2003. Experience-dependent regulation of synaptic zinc is impaired in the cortex of aged mice. Neuroscience 119:795-801. Brown CE, Seif I, De Maeyer E, Dyck RH. 2003. Altered zincergic innervation of the developing primary somatosensory cortex in monoamine-oxidase A knockout mice. Developmental Brain Research 142:19-29. Brown CE and Dyck RH. 2002. Rapid, experience-dependent changes in levels of synaptic zinc in primary somatosensory cortex of the adult mouse. Journal of Neuroscience 22:2617-2625.