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Gene Therapy for Cognitive Recovering After Ischemic Stroke

  • Johanna Gutierrez-Vargas
  • Rafael Posada-Duque
  • Gloria Patricia Cardona-GómezEmail author
Chapter
  • 771 Downloads
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Cerebrovascular accident (CVA) is the second leading cause of death in the world and the first cause of disability in adults, being a 34% of affected people younger than 65 years old. Which is an important consequence by sedentary lifestyle and a high intake of fats and sugars. One of the major shortcomings of current therapeutical approach is the lack of comorbidity studies, intervention time (less than 4.5 h) and the short time of protection or follow-up study, which unprotect for long-term sequelae in the patients. Gene therapy has been shown to be a very useful tool for the treatment of neurodegenerative diseases; specifically in cerebral ischemia there are few experimental studies, which are mentioned in this chapter. The most of them have a pretreatment approach, which does not facilitate the clinical translation, therefore, a major challenge of gene therapy is that it to be implemented as post-injury therapy, which is supported by our results using shRNAmiR carried out in adeno associated viral vector, preventing and reversing neurodegeneration, neurovascular unit uncoupling and cognitive impairment, which could be relevant in the field of translational medicine.

Keywords

Stroke Neurodegeneration Cognitive impairment Dementia Gene therapy RNA interference Translational medicine 

Abbreviations

AAV

Adeno associated viral vectors

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

BDNF

Brain-derived neurotrophic factor

CDK5

Cyclin-dependent kinase 5

CVA

Cerebrovascular accident

Glu

Glutamate

HMG-CoA

3-Hydroxy-3-methylglutaryl coenzyme A

LTD

Long term depression

LTP

Long term potentiation

MCAO

Middle cerebral artery occlusion

NFTs

Neurofibrillary tangles

NMDA

N-Methyl-D-aspartic acid

PD

Parkinson’s disease

RNAi

RNA interference

Rosc

Roscovitine

rt-PA

Recombinant tissue plasminogen activator

shRNAs

Short hairpin RNAs

TEER

Transendothelial resistance

WHO

World Health Organization

Notes

Acknowledgement

We are grateful to the Cellular and Molecular Neurobiology Area, Antioquia Neuroscience Group (GNA), University of Antioquia for constructive academic discussion. This research was supported by projects of Colciencias (code # 111551928905, # 111554531400) (GPC-G) and CODI # 2014-970 of the University of Antioquia, Republic Bank # 3494.

Statement of Conflict of Interest: The authors declare no conflict of interest.

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Authors and Affiliations

  • Johanna Gutierrez-Vargas
    • 1
  • Rafael Posada-Duque
    • 1
  • Gloria Patricia Cardona-Gómez
    • 1
    Email author
  1. 1.Cellular and Molecular Neurobiology Area, Group of Neuroscience, Faculty of MedicineSede de Investigación Universitaria (SIU), University of AntioquiaMedellínColombia

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