2015
DOI: 10.1038/jcbfm.2015.162
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Pharmacologically-Induced Neurovascular Uncoupling is Associated with Cognitive Impairment in Mice

Abstract: There is increasing evidence that vascular risk factors, including aging, hypertension, diabetes mellitus, and obesity, promote cognitive impairment; however, the underlying mechanisms remain obscure. Cerebral blood flow (CBF) is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism is known to be impaired in the aforementioned pathophysiologic conditions. To establish a direct relationship between impaired NVC and cognitive decline, we induced neurovascular uncoupling pharmacologic… Show more

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Cited by 113 publications
(158 citation statements)
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“…We posit that impaired functional hyperemia per se may play a significant causal role in irradiation-induced cognitive impairment. Experimental studies support this concept, demonstrating that pharmacologically induced selective neurovascular uncoupling in mice mimics important aspects of both age-related and WBI-induced cognitive impairment (Tarantini et al 2015). There are also studies extant linking impaired neurovascular coupling to gait dysfunction in the elderly (Sorond et al 2011).…”
Section: Discussionmentioning
confidence: 94%
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“…We posit that impaired functional hyperemia per se may play a significant causal role in irradiation-induced cognitive impairment. Experimental studies support this concept, demonstrating that pharmacologically induced selective neurovascular uncoupling in mice mimics important aspects of both age-related and WBI-induced cognitive impairment (Tarantini et al 2015). There are also studies extant linking impaired neurovascular coupling to gait dysfunction in the elderly (Sorond et al 2011).…”
Section: Discussionmentioning
confidence: 94%
“…Using the CatWalk system, the detection of paw print size and paw placement patterns during volunteer running on an illuminated glass walkway by a camera placed under the glass surface provides an automated analysis of gait function and the spatial and temporal aspects of inter-limb coordination (Tarantini et al 2015). Briefly, animals were trained to cross the walkway and then, in a dark and silent room (<20 lx of illumination), animals were tested in three consecutive runs.…”
Section: Analysis Of Gait Functionmentioning
confidence: 99%
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“…Functional hyperemia is not only responsible for increased delivery of oxygen and nutrients, it also enables effective washout of noxious substances, ensuring an optimal humoral microenvironment in the cerebral tissue. The cellular mechanisms underlying neurovascular coupling include synthesis of nitric oxide (NO) by activated neurons and/or endothelial of nitric oxide (NO) and astrocytic production of vasodilator eicosanoid metabolites, including epoxygenase-derived epoxyeicosatrienoic acids (EETs) and cyclooxygenase-derived prostaglandins (Chen et al 2014;Ma et al 1996;Peng et al 2002;Stobart et al 2013;Takano et al 2006;Tarantini et al 2015Tarantini et al , 2016Tarantini et al , 2017Toth et al 2014Toth et al , 2015aToth et al , b, 2017Tucsek et al 2014b;Ungvari et al 2017a;Zonta et al 2003). There is strong evidence that aging is associated with impairment of functional hyperemia (termed Bneurovascular uncoupling^) due to dysregulated release and/or increased degradation of NO, EETs, and prostaglandins (Stefanova et al 2013;Tarantini et al 2016;Topcuoglu et al 2009;Toth et al 2014).…”
Section: Introductionmentioning
confidence: 99%
“…Experimental studies in mouse models with pharmacological inhibition of the synthesis of NO, EETs, and prostaglandins confirm that a causal link exists between neurovascular dysfunction and cognitive impairment. In particular, pharmacologically induced neurovascular coupling was shown to result in impairment of spatial and recognition memory, mimicking the aging phenotype (Tarantini et al 2015).…”
Section: Introductionmentioning
confidence: 99%