Neuroprotective and toxic changes in microglia in neurodegenerative disease

Sawada, Makoto

doi:10.1016/s1353-8020(09)70011-2

Cited by 29 publications

(18 citation statements)

References 13 publications

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“…In fact, the elevation of MPO-like peroxidase activity has been associated with the shift of microglia from a protective to a neurotoxic phenotype. 84 This is consistent with previous findings highlighting that azithromycin significantly reduces lipopolysaccharide-induced elevation of MPO concentration in lung homogenates of mice. 85 Moreover, we previously demonstrated that the number of F4/80…”

Section: Discussionsupporting

confidence: 93%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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Section: Discussionsupporting

confidence: 93%

Neuroprotective Properties of a Macrolide Antibiotic in a Mouse Model of Middle Cerebral Artery Occlusion: Characterization of the Immunomodulatory Effects and Validation of the Efficacy of Intravenous Administration

Amantea

Certo

Petrelli

et al. 2016

ASSAY and Drug Development Technologies

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“…Microglia are commonly associated with inflammation after ischemia and were thought to be neurotoxic, although recent evidence supports a neuroprotective role of microglia, by removing cellular debris and infiltrating neutrophils, both of which are a potential source of oxidative damage. 24,25 As identified by OX42 immunoreactivity in the current study, there was an increase in the number of activated microglia after stroke, as previously reported using this same stroke model. 26 Moreover, there was also an obvious change in microglia appearance from an amoeboid shape to a phenotype exhibiting processes, when moving from the infarcted core to peri-infarct region (see Figure 5); a finding that has also been demonstrated in different models of stroke in rats and is indicative of phagocytosis of cellular debris.…”

Section: 23supporting

confidence: 89%

Angiotensin II Type 2 Receptor Stimulation Initiated After Stroke Causes Neuroprotection in Conscious Rats

McCarthy

Vinh²,

Broughton³

et al. 2012

Hypertension

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A ngiotensin II (Ang II) can bind to several receptor subtypes, thus, influencing an array of cardiovascular functions in the body. However, the 2 major receptor subtypes are the angiotensin II type 1 receptor (AT 1 R), which is thought to be responsible for most of the biological and pathological actions of Ang II, and the angiotensin II type 2 receptor (AT 2 R), which mainly opposes the actions of the AT 1 R.1 Several largescale clinical trials 2,3 have indicated that the use of AT 1 R antagonists as a method of blood pressure control in high-risk patients improves cardiac and vascular events, which results in a reduced risk of secondary events such as stroke. This is consistent with experimental studies reporting that central or peripheral pretreatment with an AT 1 R antagonist reduces postischemic inflammation and the size of the cerebral infarction together with improved behavioral symptoms. [4][5][6][7][8] Importantly, neuroprotection has been demonstrated to occur even with nonhypotensive doses of AT 1 R blockers. 9 The postulated nonvascular mechanisms of neuroprotection include inhibition of neuronal apoptosis 5 and reduced neuronal loss associated with inhibition of superoxide production and inflammation, 10 although there is likely to be a contribution from the AT 2 R during AT 1 R blockade.6,7 Indeed, several groups have reversed neuroprotection induced during AT 1 R blockade with the coadministration of an AT 2 R antagonist, suggesting that the AT 2 R is a pivotal component in the therapeutic action of AT 1 R antagonists. 6,7 In addition, mice lacking the AT 2 R show poorer outcome after stroke and are less receptive to the protective influence of AT 1 R antagonists.11,12 Thus, there is accumulating indirect evidence that suggests that the AT 2 R may have a cerebroprotective role during stroke, although little is known about direct AT 2 R stimulation in the brain.In this context, we have recently examined the neuroprotective effect of direct AT 2 R stimulation after intracerebroventricular (ICV) administration of the AT 2 R agonist CGP42112 in a conscious rat model of stroke. Our results indicate that, even in the absence of AT 1 R blockade, direct stimulation of the central AT 2 R for 5 days before and for 3 days after stroke dramatically reduces subsequent damage, both histologically and behaviorally, such that at 72 hours after stroke injury is minimal. 13 Given that patients normally present for treatment after a cerebrovascular event, a clinically relevant treatment needs to be effective when administered after a stroke has occurred. To this end, the current proof-of-principle study investigated the potential neuroprotective role of See Editorial Commentary, pp 1391-1392Abstract-We have demonstrated previously that pretreatment with an angiotensin II type 2 receptor (AT 2 R) agonist is neuroprotective against a subsequent stroke independent of any changes in blood pressure. Therefore, in the current study, we have examined the potential neuroprotective effect of AT 2 R stimulation initiated aft...

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“…Among other properties, they have the potential to release various factors that directly and/or indirectly promote regeneration in the injured nervous system. [1][2][3][4] It was the purpose of this review to elucidate the importance of the retinal microglial cells in the course, but not as the cause, of glaucomatous optic neuropathy, and to illustrate the role retinal microglial cells take in the interval between the primary damage set to the retinal ganglion cell axons, and the final death and disappearance of the ganglion cell axons and cell bodies. As the reaction of the microglial cells to a damaged retinal ganglion cell may not markedly depend on the primary causative mechanism, the features of the retinal microglial cells as described below with respect to glaucomatous optic neuropathy may also hold true for nonglaucomatous optic nerve damage such as in diabetic retinopathy or anterior ischemic optic neuropathy.…”

mentioning

confidence: 99%