Cerebral venous congestion exacerbates cerebral microhemorrhages in mice

Nyúl‐Tóth, Ádám; Fülöp, Gábor; Tarantini, Stefano; Kiss, Tamás; Ahire, Chetan; Faakye, Janet; Ungvari, Anna; Tóth, Péter; Tóth, Attila; Csiszár, Anna; Ungvári, Zoltán

doi:10.1007/s11357-021-00504-0

Cited by 17 publications

(15 citation statements)

References 80 publications

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“…Postcapillary venules drain the blood from the capillary bed to the big veins. The aging of the venous system is related to cognitive impairment (Molnár et al, 2021;Nyul-Toth et al, 2022). Each PA supplies a distinct region of the cerebral cortex, which is the "bottleneck" to control downstream CBF (Nishimura et al, 2007).…”

Section: Cerebrovascular Architecturementioning

confidence: 99%

Impact of impaired cerebral blood flow autoregulation on cognitive impairment

et al. 2022

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Although the causes of cognitive impairment are multifactorial, emerging evidence indicates that cerebrovascular dysfunction plays an essential role in dementia. One of the most critical aspects of cerebrovascular dysfunction is autoregulation of cerebral blood flow (CBF), mainly mediated by the myogenic response, which is often impaired in dementia individuals with comorbidities, such as diabetes and hypertension. However, many unsolved questions remain. How do cerebrovascular networks coordinately modulate CBF autoregulation in health and disease? Does poor CBF autoregulation have an impact on cognitive impairment, and what are the underlying mechanisms? This review summarizes the cerebral vascular structure and myogenic (a three-phase model), metabolic (O2, CO2, adenosine, and H+), and endothelial (shear stress) factors in the regulation of CBF; and the consequences of CBF dysautoregulation. Other factors contributing to cerebrovascular dysfunction, such as impaired functional hyperemia and capillary abnormalities, are included as well. Moreover, this review highlights recent studies from our lab in terms of novel mechanisms involved in CBF autoregulation and addresses a hypothesis that there is a three-line of defense for CBF autoregulation in the cerebral vasculature.

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Section: Cerebrovascular Architecturementioning

confidence: 99%

Impact of impaired cerebral blood flow autoregulation on cognitive impairment

et al. 2022

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“…33,48 In most cases, cerebral venous flow can be influenced by anatomical variations, incompetence of the jugular valve, and changes in central venous or intrathoracic pressure. 49 Previous studies have established a rodent model of cerebral venous congestion by internal and external JVL, 21,27,30 which can be adapted to study the consequences of cerebral venous congestion as they relate to BBB disruption, cerebral venous hypertension, dysregulation of CBF, and impaired learning and memory. 27 Indeed, we observed a significant increase in ICP and a decrease in CBF after JVL surgery.…”

Section: Discussionmentioning

confidence: 99%

“…To study pathological events of cerebral venous congestion, we used a surgical technique involving bilateral JVL 21,27,30 in rats to create a rodent cerebral venous congestion model (Figure 1(a) and (b)). It has been confirmed that venous outflow congestion contributes to the development of intracranial hypertension.…”

Section: Cerebral Venous Congestion Induced Spatial Learning and Memo...mentioning

confidence: 99%

Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function

Wei

Jiang

Zhou

et al. 2023

J Cereb Blood Flow Metab

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Vascular cognitive impairment (VCI) represents the second most common cause of dementia after Alzheimer's disease, and pathological changes in cerebral vascular structure and function are pivotal causes of VCI. Cognitive impairment caused by arterial ischemia has been extensively studied the whole time; the influence of cerebral venous congestion on cognitive impairment draws doctors’ attention in recent clinical practice, but the underlying neuropathophysiological alterations are not completely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in cognitive-behavioral deterioration and possible electrophysiological mechanisms. Using cerebral venous congestion rat models, we found these rats exhibited decreased long-term potentiation (LTP) in the hippocampal dentate gyrus and impaired spatial learning and memory. Based on untargeted metabolomics, N-acetyl-L-cysteine (NAC) deficiency was detected in cerebral venous congestion rats; supplementation with NAC appeared to ameliorate synaptic deficits, rescue impaired LTP, and mitigate cognitive impairment. In a cohort of cerebral venous congestion patients, NAC levels were decreased; NAC concentration was negatively correlated with subjective cognitive decline (SCD) score but positively correlated with mini-mental state examination (MMSE) score. These findings provide a new perspective on cognitive impairment and support further exploration of NAC as a therapeutic target for the prevention and treatment of VCI.

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“…CMH are increasingly recognized in T2* and SWI MRI sequences in the majority of older adults. Both preclinical and clinical studies show that advanced age significantly increases the prevalence of CMHs, which contribute to the development of VCID ( 42 – 44 , 63 , 64 , 219 , 257 , 258 ). CMHs are thought to arise due to a combination of age-associated factors that lead to increased microvascular fragility including: 1) structural defects such as impaired hypertension-induced adaptive changes in the ECM and impaired protective hypertrophy in the medial layer, 2) functional defects such as impaired myogenic autoregulation, and 3) age-related cellular and molecular changes such as increased oxidative stress and MMP activation ( 93 , 114 , 115 ).…”

Section: Role Of Gh/igf-1 In Regulation Of Cerebrovascular Functionmentioning

confidence: 99%

Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis

et al. 2023

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Age-related cerebrovascular pathologies, ranging from cerebromicrovascular functional and structural alterations to large vessel atherosclerosis, promote the genesis of vascular cognitive impairment and dementia (VCID) and exacerbate Alzheimer’s disease. Recent advances in geroscience, including results from studies on heterochronic parabiosis models, reinforce the hypothesis that cell non-autonomous mechanisms play a key role in regulating cerebrovascular aging processes. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert multifaceted vasoprotective effects and production of both hormones is significantly reduced in aging. This brief overview focuses on the role of age-related GH/IGF-1 deficiency in the development of cerebrovascular pathologies and VCID. It explores the mechanistic links among alterations in the somatotropic axis, specific macrovascular and microvascular pathologies (including capillary rarefaction, microhemorrhages, impaired endothelial regulation of cerebral blood flow, disruption of the blood brain barrier, decreased neurovascular coupling, and atherogenesis) and cognitive impairment. Improved understanding of cell non-autonomous mechanisms of vascular aging is crucial to identify targets for intervention to promote cerebrovascular and brain health in older adults.

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Cerebral venous congestion exacerbates cerebral microhemorrhages in mice

Cited by 17 publications

References 80 publications

Impact of impaired cerebral blood flow autoregulation on cognitive impairment

Impact of impaired cerebral blood flow autoregulation on cognitive impairment

Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function

Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis

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