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Aquaporin-4 and Cerebrovascular Diseases.

ABSTRACT: Cerebrovascular diseases are conditions caused by problems with brain vasculature, which have a high morbidity and mortality. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and crucial for the formation and resolution of brain edema. Considering brain edema is an important pathophysiological change after stoke, AQP4 is destined to have close relation with cerebrovascular diseases. However, this relation is not limited to brain edema due to other biological effects elicited by AQP4. Till now, multiple studies have investigated roles of AQP4 in cerebrovascular diseases. This review focuses on expression of AQP4 and the effects of AQP4 on brain edema and neural cells injuries in cerebrovascular diseases including cerebral ischemia, intracerebral hemorrhage and subarachnoid hemorrhage. In the current review, we pay more attention to the studies of recent years directly from cerebrovascular diseases animal models or patients, especially those using AQP4 gene knockout mice. This review also elucidates the potential of AQP4as an excellent therapeutic target.

SUBMITTER: Chu H

PROVIDER: S-EPMC5000647 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Aquaporin-4 and Cerebrovascular Diseases.

Chu Heling H Huang Chuyi C Ding Hongyan H Dong Jing J Gao Zidan Z Yang Xiaobo X Tang Yuping Y Dong Qiang Q

International journal of molecular sciences 20160811 8

Cerebrovascular diseases are conditions caused by problems with brain vasculature, which have a high morbidity and mortality. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and crucial for the formation and resolution of brain edema. Considering brain edema is an important pathophysiological change after stoke, AQP4 is destined to have close relation with cerebrovascular diseases. However, this relation is not limited to brain edema due to other biological effects elicited by ...[more]

PMID: 27529222

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Project description:With increased numbers of older people a higher burden of neurological disorders worldwide is predicted. Stroke and other cerebrovascular diseases do not necessarily present with different phenotypes in Africa but their incidence is rising in tandem with the demographic change in the population. Age remains the strongest irreversible risk factor for stroke and cognitive impairment. Modifiable factors relating to vascular disease risk, diet, lifestyle, physical activity and psychosocial status play a key role in shaping the current spate of stroke related diseases in Africa. Hypertension is the strongest modifiable risk factor for stroke but is also likely associated with co-inheritance of genetic traits among Africans. Somewhat different from high-income countries, strokes attributed to cerebral small vessel disease (SVD) are higher >30% among sub-Saharan Africans. Raised blood pressure may explain most of the incidence of SVD-related strokes but there are likely other contributing factors including dyslipidaemia and diabetes in some sectors of Africa. However, atherosclerotic and cardioembolic diseases combined also appear to be common subtypes as causes of strokes. Significant proportions of cerebrovascular diseases are ascribed to various forms of infectious disease including complications of human immunodeficiency virus. Cerebral SVD leads to several clinical manifestations including gait disturbance, autonomic dysfunction and depression. Pathological processes are characterized by arteriolosclerosis, lacunar infarcts, perivascular spaces, microinfarcts and diffuse white matter changes, which can now all be detected on neuroimaging. Except for isolated cases of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL, hereditary arteriopathies have so far not been reported in Africa. Prevalence estimates of vascular dementia (2-3%), delayed dementia after stroke (10-20%) and vascular cognitive impairment (30-40%) do not appear to be vastly different from those in other parts of the world. However, given the current demographic transition in both urban and rural settings these figures will likely rise. Wider application of neuroimaging modalities and implementation of stroke care in Africa will enable better estimates of SVD and other subtypes of stroke. Stroke survivors with SVD type pathology are likely to have low mortality and therefore portend increased incidence of dementia.

Project description:Background The causal relationship between gut microbiota and cerebrovascular disease remains unknown, despite several recent studies reporting an association between the two. Methods To assess this relationship, we conducted a two-sample Mendelian randomization (MR) using summary statistics data from published genome-wide association studies (GWAS). This analysis allowed us to identify bacterial taxa that may affect cerebrovascular disease. Furthermore, we performed reverse MR to further analyze the significant bacterial taxa. Finally, we conducted a two-step MR analysis to examine the mediating role of metabolic factors [systolic blood pressure (SBP), type 2 diabetes (T2D), and body mass index (BMI)] in the association between gut microbiota and cerebrovascular disease. Additionally, a series of sensitivity analyses were carried out to validate the robustness of our findings. Results Our results showed that a genetically predicted high abundance of family Porphyromonadaceae reduced the risk of intracranial aneurysms (IA). Moreover, using inverse variance weighted (IVW) estimates, we found a nominal causal relationship between seventeen gut microbiota and IA, as well as its subtypes. In the case of stroke and its subtypes, we observed a nominal causal relationship with thirteen, eleven, eleven, nine, and eight bacteria for AS, AIS, CES, LAS, and SVS, respectively. Reverse MR analysis showed no significant causal relationship between intracranial aneurysms and gut microbiota. However, we did find that genetically predicted any stroke (AS) and any ischemic stroke (AIS) reduced the abundance of family Clostridiaceae1 (OR: 0.74, 95% CI: 0.62–0.87, p = 3.39 × 10−4, and OR: 0.75, 95% CI: 0.66–0.87, p = 7.06 × 10−5, respectively). Furthermore, genetic prediction of AIS (OR: 0.87, 95% CI: 0.77–0.99, p = 3.05 × 10−2) was associated with a reduced abundance of the order Clostridiales. Moreover, genus Streptococcus exhibited effects on AS, AIS, and SVS which were mediated by T2D. Conversely, the association between genus Eubacterium brachy group and AIS was mediated by SBP. No significant heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on cerebrovascular disease. And SBP and T2D may play mediating role in this process.

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Aquaporin-4 and Cerebrovascular Diseases.

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Aquaporin-4 and Cerebrovascular Diseases.

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