High incidence of adverse cerebral blood flow responses to spreading depolarization in the aged ischemic rat brain

Menyhárt, Ákos; Makra, Péter; Szepes, Borbála É.; Tóth, Orsolya M.; Hertelendy, Péter; Bari, Ferenc; Farkas, Eszter

doi:10.1016/j.neurobiolaging.2015.08.014

Cited by 37 publications

(102 citation statements)

References 45 publications

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“…15 In addition, spontaneous SDs in the ischemic cortex of 2-year-old rats emerged less likely with respect to 9-month-old animals. 16 These findings urged us to determine at what exact age the threshold of SD elicitation starts to rise, especially in ischemic tissue.…”

Section: Electric Threshold To Elicit Spreading Depolarizationmentioning

confidence: 98%

“…13 On the other hand, the aging nervous tissue proves to be increasingly resistant to experimental SD elicitation, requiring rising concentration of K þ to trigger SD. 14,15 Similarly, the likelihood of spontaneous SD occurrence in the ischemic rat cortex decreases with age. 16 It is, however, uncertain at what age the threshold of SD elicitation starts to rise, especially in ischemic tissue.…”

Section: Introductionmentioning

confidence: 96%

“…6 We have recently demonstrated that the ischemic cerebral cortex of aged rats-in contrast with young adult ones-is excessively prone to the evolution of inverse neurovascular coupling with SD, 15 which is possibly responsible for the intensified expansion of ischemic damage in the aged brain. Yet, it remains to be shown whether the kinetics of the SD-associated CBF response varies during young adulthood.…”

Section: Introductionmentioning

confidence: 99%

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Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats

Hertelendy

Menyhárt

Makra

et al. 2016

J Cereb Blood Flow Metab

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Spreading depolarizations of long cumulative duration have been implicated in lesion development and progression in patients with stroke and traumatic brain injury. Spreading depolarizations evolve less likely in the aged brain, but it remains to be determined at what age the susceptibility to spreading depolarizations starts to decline, especially in ischemia. Spreading depolarizations were triggered by epidural electric stimulation prior and after ischemia induction in the cortex of 7-30 weeks old anesthetized rats (n ¼ 38). Cerebral ischemia was achieved by occlusion of both common carotid arteries. Spreading depolarization occurrence was confirmed by the acquisition of DC potential and electrocorticogram. Cerebral blood flow variations were recorded by laser-Doppler flowmetry. Dendritic spine density in the cortex was determined in Golgi-COX stained sections. Spreading depolarization initiation required increasingly greater electric charge with older age, a potential outcome of consolidation of cortical connections, indicated by altered dendritic spine distribution. The threshold of spreading depolarization elicitation increased with ischemia in all age groups, which may be caused by tissue acidosis and increased K þ conductance, among other factors. In conclusion, the brain appears to be the most susceptible to spreading depolarizations at adolescent age; therefore, spreading depolarizations may occur in young patients of ischemic or traumatic brain injury at the highest probability.

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Section: Electric Threshold To Elicit Spreading Depolarizationmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats

Hertelendy

Menyhárt

Makra

et al. 2016

J Cereb Blood Flow Metab

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“…The duration of SD itself has been proposed to determine the duration of SD-related hyperemia, because longer duration of the DC shift coincided with longer hyperemia [76]. Since the recovery of resting membrane potential and thus normal electrical activity of the nervous tissue requires the activity of the ATP-consuming Na + pump [32], the return of CBF to baseline after hyperemia may be postponed by the continuing energy need, reflected by the longer duration of the electric silence with SD.…”

Section: 4kinetics Of Spreading Depolarization and The Associated mentioning

confidence: 99%

“…In the ischemic brain, the CBF response to SD is more dominated by vasoconstrictive elements, leading to diminishing hyperemia and more prevalent hypoemia [33,76,77]. In the most severe form, the hypoemic element completely outweighs hyperemia, and turns into spreading ischemia [32].…”

Section: 4kinetics Of Spreading Depolarization and The Associated mentioning

confidence: 99%

Live, optical experimental neuroimaging reveals variations of the cerebral blood flow response to ischemic spreading depolarization

Bere¹

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CVN‐AD Alzheimer's mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls

Turner

Degan

Hoffmann

et al. 2021

Alzheimer's & Dementia

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We compared the efficacy of neurovascular coupling and substrate supply in cerebral cortex during severe metabolic challenges in transgenic Alzheimer's [CVN‐AD] and control [C57Bl/6] mice, to evaluate the hypothesis that metabolic insufficiency is a critical component of degeneration leading to dementia. We analyzed cerebral blood flow and metabolic responses to spreading depression (induced by K+ applied to the cortex) and anoxia across aging in CVN‐AD + C57Bl/6 genotypes. In the CVN‐AD genotype progression to histological and cognitive hallmarks of dementia is a stereotyped function of age. We correlated physiology and imaging of the cortex with the blood flow responses measured with laser doppler probes. The results show that spreading depression resulted in a hyperemic blood flow response that was dramatically reduced (24% in amplitude, 70% in area) in both middle‐aged and aged CVN‐AD mice compared to C57Bl/6 age‐matched controls. However, spreading depression amplitude and conduction velocity (≈6 mm/min) did not differ among groups. Anoxia (100% N2) showed significantly decreased (by 62%) reactive blood flow and autoregulation in aged AD‐CVN mice compared to aged control animals. Significantly reduced neurovascular coupling occurred prematurely with aging in CVN‐AD mice. Abbreviated physiological hyperemia and decreased resilience to anoxia may enhance early‐onset metabolic deficiency through decreased substrate supply to the brain. Metabolic deficiency may contribute significantly to the degeneration associated with dementia as a function of aging and regions of the brain involved.

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High incidence of adverse cerebral blood flow responses to spreading depolarization in the aged ischemic rat brain

Cited by 37 publications

References 45 publications

Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats

Advancing age and ischemia elevate the electric threshold to elicit spreading depolarization in the cerebral cortex of young adult rats

Live, optical experimental neuroimaging reveals variations of the cerebral blood flow response to ischemic spreading depolarization

CVN‐AD Alzheimer's mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls

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