Abstract-Accumulating evidence indicates a key role of inflammation in hypertension and cardiovascular disorders. However, the role of inflammatory processes in neurogenic hypertension remains to be determined. Thus, our objective in the present study was to test the hypothesis that activation of microglial cells and the generation of proinflammatory cytokines in the paraventricular nucleus (PVN) contribute to neurogenic hypertension. Intracerebroventricular infusion of minocycline, an anti-inflammatory antibiotic, caused a significant attenuation of mean arterial pressure, cardiac hypertrophy, and plasma norepinephrine induced by chronic angiotensin II infusion. This was associated with decreases in the numbers of activated microglia and mRNAs for interleukin (IL) 1␤, IL-6, and tumor necrosis factor-␣, and an increase in the mRNA for IL-10 in the PVN. Overexpression of IL-10 induced by recombinant adenoassociated virus-mediated gene transfer in the PVN mimicked the antihypertensive effects of minocycline. Furthermore, acute application of a proinflammatory cytokine, IL-1␤, into the left ventricle or the PVN in normal rats resulted in a significant increase in mean arterial pressure. Collectively, this indicates that angiotensin II induced hypertension involves activation of microglia and increases in proinflammatory cytokines in the PVN. These data have significant implications on the development of innovative therapeutic strategies for the control of neurogenic hypertension. (Hypertension. 2010;56:297-303.)Key Words: angiotensin II Ⅲ hypertension Ⅲ minocycline Ⅲ interleukin 10 Ⅲ microglia Ⅲ paraventricular nucleus Ⅲ cytokine I nflammation has been implicated in hypertension and cardiovascular diseases in both animal models and human diseases. 1,2 Increases in levels of plasma proinflammatory cytokines (PICs) and other markers of inflammation are associated with the progression of hypertension, whereas immune suppression produces beneficial outcomes. 3,4 Despite evidence for the participation of peripheral cytokines and inflammation in cardiovascular disease, little is known about their involvement in neurogenic hypertension. Studies from Francis and collaborators 5,6 have indicated that angiotensin (Ang) II-induced hypertension involves activation of tumor necrosis factor-␣ (TNF-␣) and nuclear factor B and production of reactive oxygen species in the brain. These observations have led us to propose that Ang II-induced neurogenic hypertension involves activation of microglial cells and production of PICs within the brain. Our objective in the present study was to test this hypothesis.We focused on the paraventricular nucleus (PVN) and a chronic Ang II infusion rat model of hypertension for this study, based on the following rationales. First, the PVN integrates signals/inputs from circumventricular organs and other cardiovascular-relevant brain areas and transmits them to the rostroventrolateral medulla and other downstream areas to influence sympathetic nerve activity. 7 Second, chronic Ang II infusion is an e...

Synapses between engram cells are believed to be substrates for memory storage, and the weakening or loss of these synapses leads to the forgetting of related memories. We found engulfment of synaptic components by microglia in the hippocampi of healthy adult mice. Depletion of microglia or inhibition of microglial phagocytosis prevented forgetting and the dissociation of engram cells. By introducing CD55 to inhibit complement pathways, specifically in engram cells, we further demonstrated that microglia regulated forgetting in a complement- and activity-dependent manner. Additionally, microglia were involved in both neurogenesis-related and neurogenesis-unrelated memory degradation. Together, our findings revealed complement-dependent synapse elimination by microglia as a mechanism underlying the forgetting of remote memories.

The underlying mechanisms of wound healing are complex but inflammation is one of the determining factors. Besides its traditional role in combating against infection upon injury, the characteristics and magnitude of inflammation have dramatic impacts on the pathogenesis of scar. Keloids and hypertrophic scars are pathological scars that result from aberrant wound healing. They are characterized by continuous local inflammation and excessive collagen deposition. In this review, we aim at discussing how dysregulated inflammation contributes to the pathogenesis of scar formation. Immune cells, soluble inflammatory mediators, and the related intracellular signal transduction pathways are our three subtopics encompassing the events occurring in inflammation associated with scar formation. In the end, we enumerate the current and potential medicines and therapeutics for suppressing inflammation and limiting progression to scar. Understanding the initiation, progression, and resolution of inflammation will provide insights into the mechanisms of scar formation and is useful for developing effective treatments.

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Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or L-NG-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and pro-inflammatory cytokine up-regulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration and blood pressure. Furthermore, when microglia were pre-activated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II; and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure.