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I n t e r n a t i o n a l C o n f e r e n c e o n
Neurological Disorders,
Stroke and CNS
October 22-23 , 2018
Athens , Greece
Journal of Neurology and Neuroscience
ISSN: 2171-6625
Stroke and CNS 2018
I
n ischemic stroke, vascular occlusion and energy deficit rapidly induce tissue infarct. Cell damage propagates to surrounding
tissues for several hours. This therapeutic window provides time to save neuronal cells in penumbra. To determine proteins
involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression profile in 2 mm ring around
photothrombotic infarct core induced in rat cerebral cortex by local laser irradiation after rose bengal administration. Histological
and ultrastructural studies showed edema and degeneration of neurons, glia and capillaries, which decreased gradually across
penumbra. Expression profile of 224 signalling proteins, 1, 4 or 24 hours after photothrombotic infarct comparing with untreated
contralateral cortex was studied with antibody microarrays. Diverse cellular subsystems were involved in penumbra response.
Proteomic analysis showed concerted upregulation of diverse proteins that initiate, regulate and execute apoptosis (Par4, E2F1,
p75, p38, JNK, p53, GADD153, GAD65/67, NMDAR2a, c-myc, Bcl-10, AIF, SMAC/DIABLO, PSR, caspases 3, 6 and 7). Different
anti-apoptotic (Bcl-x, p63, p21WAF-1, MDM2, ERK5, MKP-1, NEDD8) and signalling proteins that regulate cell metabolism,
functions and survival (calmodulin, CaMKIIα, CaMKIV, ERK1/2, MAKAPK2, PKCα, PKCβ, PKCμ, RAF1, protein phosphatase 1α,
ATF2, estrogen and EGF receptors) were simultaneously overexpressed. Bidirectional changes in adhesion and cytoskeleton
proteins were associated with penumbra destruction or remodelling. Proteins that regulate actin cytoskeleton (cofilin,
actopaxin, p120CTN, α-catenin, p35, myosin Va, pFAK) were up-regulated, whereas others (ezrin, tropomyosin, spectrin (α+β),
βIV-tubulin, polyglutamated β-tubulin, cytokeratins 7 and 19) were downregulated. Downregulation of syntaxin, AP2β/γ, and
adaptin β1/2 indicated impairment of vesicular transport and synaptic processes. Downregulation of Cdk6, Cdc7 kinase, Trf1,
and topoisomerase-1 showed suppression of proliferation. APP, nicastrin and β-amyloid were upregulated. These data provide
integral view on neurodegeneration or neuroprotection processes in penumbra. Some of these proteins may be potential targets
for anti-stroke therapy.
auzd@yandex.ruExpression of signaling proteins in ischemic
penumbra after photothrombotic stroke
J Neurol Neurosci 2018, Volume: 9
DOI: 10.21767/2171-6625-C3-015
Anatoly Uzdensky and Svetlana Demyanenk
Laboratory of Molecular Neurobiology, Southern Federal University, Rostov-on-Don, 344090,
Russia