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Refocusing the Brain: New Approaches in Neuroprotection Against Ischemic Injury

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Abstract

A new era for neuroprotective strategies is emerging in ischemia/reperfusion. This has forced to review the studies existing to date based in neuroprotection against oxidative stress, which have undoubtedly contributed to clarify the brain endogenous mechanisms, as well as to identify possible therapeutic targets or biomarkers in stroke and other neurological diseases. The efficacy of exogenous administration of neuroprotective compounds has been shown in different studies so far. However, something must be missing to get these treatments successfully applied in the clinical environment. Here, the mechanisms involved in neuronal protection against physiological level of ROS and the main neuroprotective signaling pathways induced by excitotoxic and ischemic stimuli are reviewed. Also, the endogenous ischemic tolerance in terms of brain self-protection mechanisms against subsequent cerebral ischemia is revisited to highlight how the preconditioning has emerged as a powerful tool to understand these phenomena. A better understanding of endogenous defense against exacerbated ROS and metabolism in nervous cells will therefore aid to design pharmacological antioxidants targeted specifically against oxidative damage induced by ischemic injury, but also might be very valuable for translational medicine.

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Acknowledgements

We are grateful to Prof. Bolaños for transmitting his enthusiasm for research; for his constant help in our professional development. We also thank A. Almeida for her commendable support. This publication was made possible by funding from the Instituto de Salud Carlos III (PI18/00103 and RD16/0019/0018); European Regional Development Fund (FEDER); Junta de Castilla y León (IES007P17; Escalera de Excelencia CLU-2017-03 Cofinanciado por el P.O. FEDER de Castilla y León 14-20); and HypoxiaNet (SAF2017-90794-REDT).

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  1. Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain

    Cristina Rodriguez, Jesús Agulla & María Delgado-Esteban

  2. Institute of Functional Biology and Genomics, University of Salamanca, CSIC, Salamanca, Spain

    Cristina Rodriguez, Jesús Agulla & María Delgado-Esteban

  3. Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca, Spain

    María Delgado-Esteban

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  1. Cristina Rodriguez
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  2. Jesús Agulla
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Correspondence to María Delgado-Esteban.

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Rodriguez, C., Agulla, J. & Delgado-Esteban, M. Refocusing the Brain: New Approaches in Neuroprotection Against Ischemic Injury. Neurochem Res 46, 51–63 (2021). https://doi.org/10.1007/s11064-020-03016-z

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