Brain Microglial Cytokines in Neurogenic Hypertension

Shi, Peng; Díez-Freire, Carlos; Jun, Joo Yun; Qi, Yanfei; Katovich, Michael J.; Li, Qiuhong; Sriramula, Srinivas; Francis, Joseph; Sumners, Colin; Raizada, Mohan K.

doi:10.1161/hypertensionaha.110.150409

Cited by 344 publications

(395 citation statements)

References 26 publications

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“…Hypertension causes activation of astrocytes and microglia and elevates expression of adhesion molecules in endothelial cells [223][224][225]. Microglia activation has been observed in angiotensin-II-induced hypertensive rats and intracerebroventricular administration of minocycline abrogated the angiotensin-II-induced hypertension [226]. Hypertension also affects inflammatory responses in the periphery.…”

Section: Hypertensionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Hypertensionmentioning

confidence: 99%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…114 Specifically, Ang II-mediated hypertension is associated with increased brain levels of TNFa, nuclear factor kB and reactive oxygen species. 128,129 Studies by Raizada and colleagues 130 suggest that Ang II infusion increases microglial cell and pro-inflammatory cytokine activation at the paraventricular nucleus, a region which receives descending neural inputs from the circumventricular organs. Notably, intracerebroventricular administration of the anti-inflammatory antibiotic minocycline inhibits the Ang II-mediated hypertension and the activation of microglia and cytokines.…”

Section: Drug-resistant Hypertension-how To Treat?mentioning

confidence: 99%

“…137 In addition, the disruption of blood-brain barrier integrity in hypertension may permit infiltration of inflammatory cells into the brain parachyma, thus precipitating microglial cell activation and elevating pro-inflammatory cytokine levels at central sites, such as the paraventricular nucleus, consequently augmenting central sympathetic outflow. 130 Aside from elevating central cytokine concentration, leukocyte accumulation within the brain microvasculature may precipitate neurogenic hypertension by raising cerebral vascular resistance, impairing perfusion and causing local tissue hypoxia (that is, Cushing response). 16,138 Neurons within the RVLM and spinal cord are known to be sensitive to hypoxia and can produce sympathoexcitation.…”

Section: Drug-resistant Hypertension-how To Treat?mentioning

confidence: 99%

The sympathetic nervous system and blood pressure in humans: implications for hypertension

2011

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A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined. Keywords: sympathetic nerve activity; neurogenic hypertension; immune-to-brain signalling The sympathetic renaissancePrimary (or essential) hypertension (termed hypertension from here on) accounts for the vast majority of hypertensive cases (B95%).1 Although the aetiology of this condition is incompletely understood, it appears that along with genetic factors, several environmental and behavioural 'hypertensiogenic' factors have been identified, such as obesity, insulin resistance, high-salt intake, low physical activity levels and stress.1 Given the elevated risk of stroke, renal failure, myocardial infarction and coronary heart disease in those afflicted with high blood pressure, the elucidation of the key pathogenic features and optimisation of effective therapeutic strategies are critical.The most common form of hypertension is neurogenic hypertension, defined as high blood pressure with sympathetic overdrive, loss of parasympathetically mediated cardiac variability and excessive angiotensin II (Ang II) activity.2 The importance of the sympathetic nervous system in the short-term regulation of blood pressure via the modulation of peripheral vascular tone and cardiac output is well established, while the role of the sympathetic nerve activity (SNA) in long-term blood pressure control is more controversial. [3][4][5] Although the concept of a potential neurogenic component to hypertension is not new, 4 it has perhaps received less attention than the renin-angiotensin system (RAS), which has been a prominent therapeutic and research target in hypertension over the past few decades. Nevertheless, the activation of the sympathetic nervous system and the RAS in hypertension appears inextricably, and reciprocally, linked. Evidence from studies in both patients and animal models of hypertension strongly implicate the chronic sympathetic neural activation in the aetiology and progression of hypertension (Figure 1). 2,[6][7][8][9] The use of regional surgical sympathectomy to treat hypertension over 50 years ago before the availability of antihypertensive medications that lower sympathetic activity provides an early indication of the clinical appreciation for a significant neurogenic component to hypertension.10 Recent clini...

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“…HEART FAILURE AS CIRCULATORY HOMEOSTASIS FAILURE pro-inflammatory cytokines, [65][66][67][68][69] perivascular macrophages, 70,71) transcription factor nuclear factor kappa B, 72) and microglial cytokines 73,74) have been reported as being important factors of sympathoexcitation.…”

Section: Central Mechanisms Of Sympathoexcitation In Heart Failurementioning

confidence: 99%

Heart Failure as a Disruption of Dynamic Circulatory Homeostasis Mediated by the Brain

Kishi

2016

Int. Heart J.

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SummaryCirculatory homeostasis is associated with interactions between multiple organs, and the disruption of dynamic circulatory homeostasis could be considered as heart failure. The brain is the central unit integrating neural and neurohormonal information from peripheral organs and controlling peripheral organs using the autonomic nervous system. Heart failure is worsened by abnormal sympathoexcitation associated with baroreflex failure and/or chemoreflex activation, and by vagal withdrawal, and autonomic modulation therapies have benefits for heart failure. Recently, we showed that baroreflex failure induces striking volume intolerance independent of left ventricular dysfunction. Many studies have indicated that an overactive renin-angiotensin system, excess oxidative stress and excess inflammation, and/or decreased nitric oxide in the brain cause sympathoexcitation in heart failure. We have demonstrated that angiotensin II type 1 receptor (AT 1 R)-induced oxidative stress in the rostral ventrolateral medulla (RVLM), which is known as a vasomotor center, causes prominent sympathoexcitation in heart failure model rats. Interestingly, systemic infusion of angiotensin II directly affects brain AT 1 R with sympathoexcitation and left ventricular diastolic dysfunction. Moreover, we have demonstrated that targeted deletion of AT 1 R in astrocytes strikingly improved survival with prevention of left ventricular remodeling and sympathoinhibition in myocardial infarction-induced heart failure. From these results, we believe it is possible that AT 1 R in astrocytes, not in neurons, have a key role in the pathophysiology of heart failure. We would like to propose a novel concept that the brain works as a central processing unit integrating neural and hormonal input, and that the disruption of dynamic circulatory homeostasis mediated by the brain causes heart failure. (Int Heart J 2016; 57: 145-149)

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Brain Microglial Cytokines in Neurogenic Hypertension

Cited by 344 publications

References 26 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

The sympathetic nervous system and blood pressure in humans: implications for hypertension

Heart Failure as a Disruption of Dynamic Circulatory Homeostasis Mediated by the Brain

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