?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F27497%2F&rft.title=Understanding+the+neuropathogenesis+of+Rift+Valley+Fever+using+in+vitro+and+in+vivo+models&rft.creator=Kujawa%2C+Michael&rft.description=Rift+Valley+Fever+Virus+(RFVF)+is+a+mosquito-borne+pathogen+found+primarily+within+Africa+that+is+capable+of+causing+both+human+and+animal+illness.++In+humans%2C+RVFV+can+cause+different+clinical+diseases%2C+with+encephalitis+being+one+of+the+more+severe+outcomes.++In+order+to+study+the+neuropathogenic+mechanisms+of+RVFV%2C+our+laboratory+developed+the+Lewis+rat+model.++When+exposed+to+RVFV+via+the+aerosol+route%2C+Lewis+rats+develop+a+uniformly+lethal+encephalitic+disease+with+neurological+symptoms.++The+goal+of+this+research+study+is+to+compare+in+vitro+brain+cell+culture+systems+to+the+in+vivo+brain+environment+of+rats+infected+with+RVFV%2C+further+define+the+systemic+(serum)+and+regional+(CNS)+cytokine+dysregulation+that+occurs+in+infected+rats%2C+and+explore+the+neuropathogenesis+using+an+animal+model.++The+results+presented+here+demonstrate+that+SH-SY5Y+neuronal+cells+and+HBMEC+cells+were+as+permissive+for+viral+replication+as+Vero+E6+and+BHK-21+cells%2C+two+cell+lines+that+are+defective+in+the+antiviral+response.++The+high+permissivity+of+these+cells+for+RVFV+replication+suggests+both+cell+types+may+be+targeted+in+vivo+and+play+a+role+in+disease+progression.++Cytokines+produced+from+SH-SY5Y+and+HBMEC+cells+in+vitro+are+similar+to+the+cytokine+storm+produced+in+infected+rats+during+the+encephalitic+stage+of+disease.++MMP-9+may+be+a+potential+factor+in+compromising+brain+vasculature%2C+and+current+studies+are+continuing+to+evaluate+the+effect+of+virus+infection+on+blood+brain+barrier+integrity.++Experiments+examining+the+blood+brain+barrier+integrity+in+infected+rats+suggest+that+virus+arrives+in+the+CNS+via+the+olfactory+bulb+prior+to+breakdown+of+the+blood+brain+barrier.++Taken+together%2C+the+neuropathological+route+of+infection+appears+to+enter+through+the+olfactory+epithelium+early+after+exposure+and+progresses+directly+into+the+brain+tissue.++The+public+health+significance+of+this+project+is+supported+by+the+creation+of+a+novel+Rift+Valley+Fever+in+vitro+neuronal+model%2C+as+well+as+the+exploration+of+the+neuropathogenesis+during+infection+that+has+previously+been+unknown.&rft.date=2016-06-29&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F27497%2F1%2FMichael_Kujawa_Thesis_2016_Final.pdf&rft.identifier=++Kujawa%2C+Michael++(2016)+Understanding+the+neuropathogenesis+of+Rift+Valley+Fever+using+in+vitro+and+in+vivo+models.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++