scholarly journals The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

2017 ◽  
Vol 144 (5) ◽  
pp. 582-594 ◽  
Author(s):  
Elizabeth Dao ◽  
Ging-Yuek Robin Hsiung ◽  
Teresa Liu-Ambrose
Keyword(s):  
Cognitive Impairment ◽  
Vascular Cognitive Impairment

The role of high-mobility group box protein 1 in chronic cerebral hypoperfusion-induced vascular cognitive impairment animals

2019 ◽  
Author(s):  
Amelia Nur Vidyanti ◽  
Jia-Yu Hsieh ◽  
Kun-Ju Lin ◽  
Yao-Ching Fang ◽  
Ismail Setyopranoto ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
High Mobility ◽  
Vascular Cognitive Impairment ◽  
High Mobility Group ◽  
Cerebral Hypoperfusion ◽  
Hippocampal Atrophy ◽  
Amyloid Pet ◽  
Knock Out

Abstract Background: The molecular mechanisms of vascular cognitive impairment (VCI) are diverse and still in puzzle. VCI could be attributed to chronic cerebral hypoperfusion (CCH). CCH may cause a cascade of reactions involved in ischemia and neuro-inflammation which plays important roles in the pathophysiology of VCI. High-mobility group box protein 1 (HMGB1) is a non-histone protein that serves as a damage-associated molecular signal leading to cascades of inflammation. Increased level of HMGB1 has been established in the acute phase of CCH. However, the role of HMGB1 at the chronic phase of CCH remains elucidated. Methods: We performed modified bilateral common carotid artery occlusion (BCCAO) in C57BL/6 mice to induce CCH. We examined the cerebral blood flow (CBF) reduction by laser doppler flowmetry, the protein expression of HMGB1 and its pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) by western blotting and immunohistochemistry. The brain pathology was assessed by 7T-animal MRI and amyloid-b accumulation was assessed by amyloid-PET scanning. We further evaluated the effect of HMGB1 suppression by injecting CRISPR/Cas9 knock-out plasmid intra-hippocampus bilaterally. Results: There were reduction of CBF up to 50% which persisted three months after CCH. The modified-BCCAO animals developed significant cognitive decline. The 7T-MRI image showed hippocampal atrophy, although the amyloid-PET showed no significant amyloid-beta accumulation. Increased protein levels of HMGB1, TNF-a and IL-1b were found three months after BCCAO. HMGB1 suppression by CRISPR/Cas9 knock-out plasmid restored the CBF, IL-1B, TNF-alpha, IL-6, and attenuated hippocampal atrophy and cognitive decline. Conclusion: HMGB1 plays a pivotal role in the pathophysiology of the animal model of CCH and it might be a candidate as therapeutic targets of VCI.

scholarly journals Role of HMGB1 in an Animal Model of Vascular Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion

2020 ◽  
Vol 21 (6) ◽  
pp. 2176 ◽  
Author(s):  
Amelia Nur Vidyanti ◽  
Jia-Yu Hsieh ◽  
Kun-Ju Lin ◽  
Yao-Ching Fang ◽  
Ismail Setyopranoto ◽  
...  
Keyword(s):  
Animal Model ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Chronic Phase ◽  
Vascular Cognitive Impairment ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Hippocampal Atrophy ◽  
Tnf Α

The pathophysiology of vascular cognitive impairment (VCI) is associated with chronic cerebral hypoperfusion (CCH). Increased high-mobility group box protein 1 (HMGB1), a nonhistone protein involved in injury and inflammation, has been established in the acute phase of CCH. However, the role of HMGB1 in the chronic phase of CCH remains unclear. We developed a novel animal model of CCH with a modified bilateral common carotid artery occlusion (BCCAO) in C57BL/6 mice. Cerebral blood flow (CBF) reduction, the expression of HMGB1 and its proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, and IL-6), and brain pathology were assessed. Furthermore, we evaluated the effect of HMGB1 suppression through bilateral intrahippocampus injection with the CRISPR/Cas9 knockout plasmid. Three months after CCH induction, CBF decreased to 30–50% with significant cognitive decline in BCCAO mice. The 7T-aMRI showed hippocampal atrophy, but amyloid positron imaging tomography showed nonsignificant amyloid-beta accumulation. Increased levels of HMGB1, TNF-α, IL-1β, and IL-6 were observed 3 months after BCCAO. HMGB1 suppression with CRISPR/Cas9 knockout plasmid restored TNF-α, IL-1β, and IL-6 and attenuated hippocampal atrophy and cognitive decline. We believe that HMGB1 plays a pivotal role in CCH-induced VCI pathophysiology and can be a potential therapeutic target of VCI.

scholarly journals The etiology, manifestations, and therapy of chronic cerebrovascular diseases

2020 ◽  
Vol 12 (5) ◽  
pp. 84-91
Author(s):  
A. G. Gogoleva ◽  
V. V. Zakharov
Keyword(s):  
Cognitive Impairment ◽  
Pathological Condition ◽  
Clinical Manifestations ◽  
Vascular Cognitive Impairment ◽  
Cerebrovascular Diseases ◽  
International Standards ◽  
Amyloid Angiopathy ◽  
Neuroradiological Diagnosis ◽  
Genetically Determined

The paper presents the current etiopathogenetic classification of chronic cerebrovascular diseases (CVD) and discusses the role of hypertension, cerebral amyloid angiopathy, and genetically determined syndromes in the development of this pathological condition. It gives recommendations for the neuroradiological diagnosis of chronic CVD in accordance with the international standards. The paper discusses the clinical manifestations of chronic CVD, primarily vascular cognitive impairment. It discusses international guidelines for the examination and treatment of patients with chronic CVD, as well as the rules for stroke prevention in this patient cohort. The possibilities of pathogenetically based therapy in decreasing the severity of vascular cognitive impairment in the presence of chronic CVD are also highlighted.

scholarly journals Aging exacerbates hypertension‐induced cerebromicrovascular injury in mice: role of autoregulatory dysfunction in the development of vascular cognitive impairment

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Peter Toth ◽  
Zsuzsanna Tucsek ◽  
Danuta Sosnowska ◽  
Tripti Gautam ◽  
Matthew Mitschelen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vascular Cognitive Impairment

scholarly journals The role of inflammasomes in vascular cognitive impairment

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Luting Poh ◽  
Wei Liang Sim ◽  
Dong-Gyu Jo ◽  
Quynh Nhu Dinh ◽  
Grant R. Drummond ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Critical Role ◽  
Disease Onset ◽  
The Elderly ◽  
Vascular Cognitive Impairment ◽  
Cerebral Hypoperfusion ◽  
Early Event ◽  
Cellular Mechanisms ◽  
Structural Brain Damage

AbstractThere is an increasing prevalence of Vascular Cognitive Impairment (VCI) worldwide, and several studies have suggested that Chronic Cerebral Hypoperfusion (CCH) plays a critical role in disease onset and progression. However, there is a limited understanding of the underlying pathophysiology of VCI, especially in relation to CCH. Neuroinflammation is a significant contributor in the progression of VCI as increased systemic levels of the proinflammatory cytokine interleukin-1β (IL-1β) has been extensively reported in VCI patients. Recently it has been established that CCH can activate the inflammasome signaling pathways, involving NLRP3 and AIM2 inflammasomes that critically regulate IL-1β production. Given that neuroinflammation is an early event in VCI, it is important that we understand its molecular and cellular mechanisms to enable development of disease-modifying treatments to reduce the structural brain damage and cognitive deficits that are observed clinically in the elderly. Hence, this review aims to provide a comprehensive insight into the molecular and cellular mechanisms involved in the pathogenesis of CCH-induced inflammasome signaling in VCI.

scholarly journals Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment

2019 ◽  
Vol 316 (5) ◽  
pp. H1124-H1140 ◽  
Author(s):  
Gabor A. Fulop ◽  
Stefano Tarantini ◽  
Andriy Yabluchanskiy ◽  
Andrea Molnar ◽  
Calin I. Prodan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Arteries ◽  
Vascular Cognitive Impairment ◽  
Cerebral Veins ◽  
Older Individuals ◽  
Low Velocity ◽  
Venous Circulation ◽  
Age Related ◽  
The Brain

There has been an increasing appreciation of the role of vascular contributions to cognitive impairment and dementia (VCID) associated with old age. Strong preclinical and translational evidence links age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. The low-pressure, low-velocity, and large-volume venous circulation of the brain also plays critical roles in the maintenance of homeostasis in the central nervous system. Despite its physiological importance, the role of age-related alterations of the brain venous circulation in the pathogenesis of vascular cognitive impairment and dementia is much less understood. This overview discusses the role of cerebral veins in the pathogenesis of VCID. Pathophysiological consequences of age-related dysregulation of the cerebral venous circulation are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages of venous origin, altered production of cerebrospinal fluid, impaired function of the glymphatics system, dysregulation of cerebral blood flow, and ischemic neuronal dysfunction and damage. Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for developing new preventive, diagnostic, and therapeutic approaches to preserve brain health in older individuals.

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