**Author details**

*Neuroprotection - New Approaches and Prospects*

paradigm.

**5. Future directions**

and human disease [9].

cerebrovascular disease and cognitive decline.

fed a HFD as the ischemic periods became longer. During the OGTT, insulin levels were significantly lower in gerbils subjected to BCCAO than in sham-operated controls. In addition, insulin secretion decrease was elevated the most after 28 days of HFD in ischemic gerbils [57]. These interesting findings using a combination of rodent models suggest that ischemic damage is a risk factor for glucose homeostasis, which might be worsened by the experimental induction of MetS in a HFD

Scientific findings combining rodent models have shown that chronic MetS is associated with poor stroke outcomes following experimental cerebrovascular events [58] since HFD or the way of inducing MetS modulates ischemic mechanisms of brain damage [59]. Also, experimental CBF restriction seems to hamper glucose homeostasis, posing a risk factor for developing MetS. When artery occlusion models are followed by the experimental induction of metabolic dysfunction features, the resulting MetS might exacerbate previously ischemia-induced glucose deregulation [57]. Therefore, combining experimental models offers an interesting scientific paradigm for elucidating the complexity of pathophysiological mechanisms underlying chronic cerebrovascular disease. In terms of Zhao and Gong [28], differential clinical scenarios may coexist in chronic pathologies where risk factors rarely exist alone or may even exert a causative role in some patients while acting as a consequence in others. In this regard, experimental studies using the combined application of murine models could help to close the gap between rodent models

However, this complex translational perspective is still necessary for studying the interaction between MetS and CCH inducing neurodegeneration. Although brain microvascular dysfunction has been confirmed in several murine models of MetS, including HFD [60, 61], Zucker [62], and SHR rats [63], whether MetS causes cognitive impairment due to a decrease in CBF has not been fully addressed yet [64]. In addition, since protein misfolding is a hallmark of neurodegenerative diseases [65], dissecting the exact role of MetS in association with CCH in protein aggregation represents a relevant challenge in the field. Detailed studies on the time-dependent proteostatic changes after experimental MetS and CCH will shed light on the roles and mechanisms of these clinical conditions in the establishment of VCID and AD. Furthermore, these studies will contribute to testing proteinremodeling factors [12] as putative neuroprotective agents for the prevention of

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María I. Herrera1,2†\*, Juan P. Luaces2†, Lucas D. Udovin2 , Nicolás Toro-Urrego2 , Matilde Otero-Losada2† and Francisco Capani2,3,4†

1 Centro de Investigaciones en Psicología y Psicopedagogía, Facultad de Psicología y Psicopedagogía, Universidad Católica Argentina, Buenos Aires, Argentina

2 Instituto de Investigaciones Cardiológicas, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, ININCA, UBA-CONICET, Buenos Aires, Argentina

3 Facultad de Medicina, Universidad Católica Argentina, Buenos Aires, Argentina

4 Universidad Autónoma de Chile, Santiago de Chile, Chile

\*Address all correspondence to: ines\_herrera@uca.edu.ar

† Share authorship.

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
