Age-related reduction of cerebral ischemic preconditioning: myth or reality?

Della-Morte, David; Cacciatore, Francesco; Salsano, Elisa; Pirozzi, Gilda; Genio, Maria Teresa Del; D'Antonio, Iole; Palmirotta, Raffaele; Guadagni, Fiorella; Rundek, Tatjana; Abete, Pasquale

doi:10.2147/cia.s47462

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…The other strategy is neuroprotection targeting various components of the cascade during ischemic insult, which is supported by preclinical data for many agents (Fisher, 2011; Dirnagl and Endres, 2014; Fisher and Saver, 2015). Unfortunately, all prior drug development of neuroprotective agents has been unsuccessful, no neuroprotective drug demonstrated unequivocal efficacy in clinical trials (Fisher, 2006; Hossmann, 2006; Della-Morte et al, 2013).…”

Section: Translational Potential Of Ginseng and Ginsenosides In Strokmentioning

confidence: 99%

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

et al. 2019

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Stroke is one of the leading causes of death and long-term disability worldwide. However, effective therapeutic approaches are still limited. The disruption of blood supply triggers complicated temporal and spatial events involving hemodynamic, biochemical, and neurophysiologic changes, eventually leading to pathological disturbance and diverse clinical symptoms. Ginseng ( Panax ginseng ), a popular herb distributed in East Asia, has been extensively used as medicinal and nutritional supplements for a variety of disorders worldwide. In recent years, ginseng has displayed attractive beneficial effects in distinct neurological disorders including stroke, involving multiple protective mechanisms. In this article, we reviewed the literature on ginseng studies in the experimental stroke field, particularly focusing on the in vivo evidence on the preventive or therapeutic efficacy and mechanisms of ginseng and ginsenosides in various stroke models of mice and rats. We also summarized the efficacy and underlying mechanisms of ginseng and ginsenosides on short- and long-term stroke outcomes.

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Section: Translational Potential Of Ginseng and Ginsenosides In Strokmentioning

confidence: 99%

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

et al. 2019

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“…Aging leads to loss of viability, an increase in vulnerability, and a progressive decrease in the endogenous mechanisms of defense. IPC is one of the most important endogenous protective mechanism against ischemia, but it decreases with aging [98]. An in-vivo study using young and aged rats (4 and 24 months) subjected to IPC (3-min ischemia) followed by 10-min ischemia, through the assessments of histology and the immunoreactivity of N-methyl-D-aspartic acid receptor 1 and caspase-3 active peptide in the hippocampal CA1 region performed 8 days after full ischemia, clearly demonstrated that the degree of cerebral protection against ischemia was reduced in the aged and preconditioned rats compared with the young rat [99].…”

Section: Age-related Differences Of Pkcs In Brainmentioning

confidence: 99%

“…Mechanisms to explain the age-related reduction of cerebral IPC may be multiple and include the physiological reduction in neurons, mitochondrial dysfunction, increase in oxidative stress, and alterations in hormonal profiles [98]. PKCs and their isoforms have been linked to IPC pathways of protection.…”

Section: Age-related Differences Of Pkcs In Brainmentioning

confidence: 99%

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Pastore

Pacifici

Dave

et al. 2019

IJMS

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Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s Disease (AD) and cerebral ischemia. Specifically ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as ψεReceptor for Activated C-Kinase (ψεRACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of δPKC and γPKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.

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“…These two phases of IT brought about by preconditioning possibly work by diverse mechanisms and in varied time frames in different tissues of the brain [12]. Factors that may affect the scope of CPC include age, gender, and strain of the animals used as models for cerebral ischemia [11,13].…”

Section: Understanding Cerebral Preconditioningmentioning

confidence: 99%

Cerebral Ischemic Preconditioning: the Road So Far…

Sangwan

Sharma

et al. 2015

Mol Neurobiol

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Cerebral preconditioning constitutes the brain's adaptation to lethal ischemia when first exposed to mild doses of a subtoxic stressor. The phenomenon of preconditioning has been largely studied in the heart, and data from in vivo and in vitro models from past 2-3 decades have provided sufficient evidence that similar machinery exists in the brain as well. Since preconditioning results in a transient protective phenotype labeled as ischemic tolerance, it can open many doors in the medical warfare against stroke, a debilitating cerebrovascular disorder that kills or cripples thousands of people worldwide every year. Preconditioning can be induced by a variety of stimuli from hypoxia to pharmacological anesthetics, and each, in turn, induces tolerance by activating a multitude of proteins, enzymes, receptors, transcription factors, and other biomolecules eventually leading to genomic reprogramming. The intracellular signaling pathways and molecular cascades behind preconditioning are extensively being investigated, and several first-rate papers have come out in the last few years centered on the topic of cerebral ischemic tolerance. However, translating the experimental knowledge into the clinical scaffold still evades practicality and faces several challenges. Of the various preconditioning strategies, remote ischemic preconditioning and pharmacological preconditioning appears to be more clinically relevant for the management of ischemic stroke. In this review, we discuss current developments in the field of cerebral preconditioning and then examine the potential of various preconditioning agents to confer neuroprotection in the brain.

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Age-related reduction of cerebral ischemic preconditioning: myth or reality?

Cited by 12 publications

References 58 publications

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Cerebral Ischemic Preconditioning: the Road So Far…

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