RGD Reference Report - Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat. - Rat Genome Database

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Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat.

Authors: Markosyan, Vage  Safiullov, Zufar  Izmailov, Andrei  Fadeev, Filip  Sokolov, Mikhail  Kuznetsov, Maksim  Trofimov, Dmitry  Kim, Evgeny  Kundakchyan, Grayr  Gibadullin, Airat  Salafutdinov, Ilnur  Nurullin, Leniz  Bashirov, Farid  Islamov, Rustem 
Citation: Markosyan V, etal., Int J Mol Sci. 2020 Sep 18;21(18). pii: ijms21186858. doi: 10.3390/ijms21186858.
RGD ID: 40924633
Pubmed: PMID:32962079   (View Abstract at PubMed)
PMCID: PMC7558841   (View Article at PubMed Central)
DOI: DOI:10.3390/ijms21186858   (Journal Full-text)

Currently, the main fundamental and clinical interest for stroke therapy is focused on developing a neuroprotective treatment of a penumbra region within the therapeutic window. The development of treatments for ischemic stroke in at-risk patients is of particular interest. Preventive gene therapy may significantly reduce the negative consequences of ischemia-induced brain injury. In the present study, we suggest the approach of preventive gene therapy for stroke. Adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and neural cell adhesion molecule (NCAM) or gene engineered umbilical cord blood mononuclear cells (UCB-MC) overexpressing recombinant VEGF, GDNF, and NCAM were intrathecally injected before distal occlusion of the middle cerebral artery in rats. Post-ischemic brain recovery was investigated 21 days after stroke modelling. Morphometric and immunofluorescent analysis revealed a reduction of infarction volume accompanied with a lower number of apoptotic cells and decreased expression of Hsp70 in the peri-infarct region in gene-treated animals. The lower immunopositive areas for astrocytes and microglial cells markers, higher number of oligodendrocytes and increased expression of synaptic proteins suggest the inhibition of astrogliosis, supporting the corresponding myelination and functional recovery of neurons in animals receiving preventive gene therapy. In this study, for the first time, we provide evidence of the beneficial effects of preventive triple gene therapy by an adenoviral- or UCB-MC-mediated intrathecal simultaneous delivery combination of vegf165, gdnf, and ncam1 on the preservation and recovery of the brain in rats with subsequent modelling of stroke.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NCAM1Humanmiddle cerebral artery infarction treatmentIMP  RGD 
Ncam1Ratmiddle cerebral artery infarction treatmentISONCAM1 (Homo sapiens) RGD 
Ncam1Mousemiddle cerebral artery infarction treatmentISONCAM1 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ncam1  (neural cell adhesion molecule 1)

Genes (Mus musculus)
Ncam1  (neural cell adhesion molecule 1)

Genes (Homo sapiens)
NCAM1  (neural cell adhesion molecule 1)


Additional Information