Hippocampus is more susceptible to hypoxic injury: has the Rosetta Stone of regional variation in neurovascular coupling been deciphered?

Zhang, Huawei; Roman, Richard J.; Fan, Fan

doi:10.1007/s11357-021-00449-4

Cited by 35 publications

(23 citation statements)

References 29 publications

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“…It has also been shown that neurovascular coupling and oxygenation are lower in the hippocampus than in the cortex under pathological conditions such as stroke. It is suggested that the hippocampus is more susceptible to hypoxic injury in the presence of neurovascular coupling damage [ 8 ]. The pathological features of the hippocampus and cortex are different and correlated during ischemic injury.…”

Section: Introductionmentioning

confidence: 99%

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

Jiang

Jiao

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (t-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated.

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Section: Introductionmentioning

confidence: 99%

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

Jiang

Jiao

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Another possible explanation is that the effect of hypoxia on hippocampal neurons could be complex. While the hippocampus is more susceptible to acute hypoxic injury (Zhang et al, 2022 ), chronic intermittent hypobaric hypoxia could restore hippocampal function and may serve as a potential treatment for epilepsy-induced cognitive impairments (Sun et al, 2020 ). Taken together, the outcome of brain hypoxia may depend on the type, severity, exposure duration, and frequency of hypoxia (Burtscher et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Hippocampal adaptation to high altitude: a neuroanatomic profile of hippocampal subfields in Tibetans and acclimatized Han Chinese residents

Zhang

Ji²,

Li³

et al. 2022

Front. Neuroanat.

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The hippocampus is highly plastic and vulnerable to hypoxia. However, it is unknown whether and how it adapts to chronic hypobaric hypoxia in humans. With a unique sample of Tibetans and acclimatized Han Chinese individuals residing on the Tibetan plateau, we aimed to build a neuroanatomic profile of the altitude-adapted hippocampus by measuring the volumetric differences in the whole hippocampus and its subfields. High-resolution T1-weighted magnetic resonance imaging was performed in healthy Tibetans (TH, n = 72) and healthy Han Chinese individuals living at an altitude of more than 3,500 m (HH, n = 27). In addition, healthy Han Chinese individuals living on a plain (HP, n = 72) were recruited as a sea-level reference group. Whereas the total hippocampal volume did not show a significant difference across groups when corrected for age, sex, and total intracranial volume, subfield-level differences within the hippocampus were found. Post hoc analyses revealed that Tibetans had larger core hippocampal subfields (bilateral CA3, right CA4, right dentate gyrus); a larger right hippocampus–amygdala transition area; and smaller bilateral presubiculum, right subiculum, and bilateral fimbria, than Han Chinese subjects (HH and/or HP). The hippocampus and all its subfields were found to be slightly and non-significantly smaller in HH subjects than in HP subjects. As a primary explorational study, our data suggested that while the overall hippocampal volume did not change, the core hippocampus of Tibetans may have an effect of adaptation to chronic hypobaric hypoxia. However, this adaptation may have required generations rather than mere decades to accumulate in the population.

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“…This is likely compounded by the fact that the hippocampus is one of the most susceptible brain regions to hypoxic and ischemic injury. 26,27 Thus, maintenance of appropriate hippocampal perfusion, including basal blood flow and activity-dependent changes in blood flow is critical to preserving healthy memory and cognitive function.…”

Section: The Vascular Supply Of the Hippocampusmentioning

confidence: 99%

Hippocampal Vascular Supply and Its Role in Vascular Cognitive Impairment

Johnson

2023

Stroke

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The incidence of age-related dementia is increasing as the world population ages and due to lack of effective treatments for dementia. Vascular contributions to cognitive impairment and dementia are increasing as the prevalence of pathologies associated with cerebrovascular disease rise, including chronic hypertension, diabetes, and ischemic stroke. The hippocampus is a bilateral deep brain structure that is central to learning, memory, and cognitive function and highly susceptible to hypoxic/ischemic injury. Compared with cortical brain regions such as the somatosensory cortex, less is known about the function of the hippocampal vasculature that is critical in maintaining neurocognitive health. This review focuses on the hippocampal vascular supply, presenting what is known about hippocampal hemodynamics and blood-brain barrier function during health and disease, and discusses evidence that supports its contribution to vascular cognitive impairment and dementia. Understanding vascular-mediated hippocampal injury that contributes to memory dysfunction during healthy aging and cerebrovascular disease is essential to develop effective treatments to slow cognitive decline. The hippocampus and its vasculature may represent one such therapeutic target to mitigate the dementia epidemic.

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Hippocampus is more susceptible to hypoxic injury: has the Rosetta Stone of regional variation in neurovascular coupling been deciphered?

Cited by 35 publications

References 29 publications

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

Hippocampal adaptation to high altitude: a neuroanatomic profile of hippocampal subfields in Tibetans and acclimatized Han Chinese residents

Hippocampal Vascular Supply and Its Role in Vascular Cognitive Impairment

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