Transoceanic Visual Exchange

Transoceanic Visual Exchange (TVE) aims to negotiate the in-between space of cultural communities outside of traditional geo-political zones of encounter and trade. The project is centred on developing a survey of recent film and video works – screenings, installations and expanded cinema – by contemporary artists that are shown in three participating regions every edition, with an accompanying digital exhibition space. A key aspect of the Transoceanic Visual Exchange project (TVE) is to integrate community voice into its curatorial framework. This is in order to explore the effectiveness of a lateral approach to curatorial practice, as opposed to the traditional hierarchical approach. Working between the Caribbean, Africa and Aotearoa, Transoceanic Visual Exchange (TVE) aims to negotiate the in-between space of our cultural communities outside of traditional geo-political zones of encounter and trade. We are developing a survey of recent film and video works – screenings, installations and expanded cinema – by contemporary artists that will be shown in Barbados, Auckland and Lagos. The three spaces involved – Fresh Milk, VAN Lagos and RM – first met as participants of International Artists Initiated, a programme organized and facilitated by David Dale Gallery, Glasgow, in July 2014. TVE intends to build upon relations established during this initial encounter and open up greater pathways of visibility, discourse and knowledge production between the artist run initiatives and their regional communities. In 2017 the Transoceanic Visual Exchange was coordinated by Natalie McGuide and Katherine Kennedy (Barbados) and Torika Bolatagici (Melbourne)

Microglial Activation Is Modulated by Captopril: in Vitro and in Vivo Studies

The renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (Cap) are predominantly used for the management of hypertension. All of the components of the RAS have also been identified in brain. Centrally located hormones such as Ang II can induce glial inflammation. Moreover, in Alzheimer’s disease (AD) models, where glial inflammation occurs and is thought to contribute to the propagation of the disease, increased levels of Ang II and ACE have been detected. Interestingly, ACE overexpression in monocytes, migrating to the brain was shown to prevent AD cognitive decline. However, the specific effects of captopril on glial inflammation and AD remain obscure. In the present study, we investigated the effect of captopril, given at a wide concentration range, on inflammatory mediators released by lipopolysaccharide (LPS)-treated glia. In the current study, both primary glial cells and the BV2 microglial cell line were used. Captopril decreased LPS-induced nitric oxide (NO) release from primary mixed glial cells as well as regulating inducible NO synthase (iNOS) expression, NO, tumor necrosis factor-α (TNF-α) and induced interleukin-10 (IL-10) production by BV2 microglia. We further obtained data regarding intranasal effects of captopril on cortical amyloid β (Aβ) and CD11b expression in 5XFAD cortex over three different time periods. Interestingly, we noted decreases in Aβ burden in captopril-treated mice over time which was paralleled by increased microglial activation. These results thus shed light on the neuroprotective role of captopril in AD which might be related to modulation of microglial activation

Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies.

The circulating renin-angiotensin system (RAS), including the biologically active angiotensin II, is a fundamental regulatory mechanism of blood pressure conserved through evolution. Angiotensin II components of the RAS have also been identified in the brain. In addition to pro-inflammatory cytokines, neuromodulators, such as angiotensin II can induce (through angiotensin type 1 receptor (AT1R)) some of the inflammatory actions of brain glial cells and influence brain inflammation. Moreover, in Alzheimer's disease (AD) models, where neuroinflammation occurs, increased levels of cortical AT1Rs have been shown. Still, the precise role of RAS in neuroinflammation is not completely clear. The overall aim of the present study was to elucidate the role of RAS in the modulation of glial functions and AD pathology. To reach this goal, the specific aims of the present study were a. to investigate the long term effect of telmisartan (AT1R blocker) on tumor necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and nitric oxide (NO) release from glial cells. b. to examine the effect of intranasally administered telmisartan on amyloid burden and microglial activation in 5X familial AD (5XFAD) mice. Telmisartan effects in vivo were compared to those of perindopril (angiotensin converting enzyme inhibitor). Long-term-exposure of BV2 microglia to telmisartan significantly decreased lipopolysaccharide (LPS) -induced NO, inducible NO synthase, TNF-α and IL1-β synthesis. The effect of Telmisartan on NO production in BV2 cells was confirmed also in primary neonatal rat glial cells. Intranasal administration of telmisartan (1 mg/kg/day) for up to two months significantly reduced amyloid burden and CD11b expression (a marker for microglia) both in the cortex and hipoccampus of 5XFAD. Based on the current view of RAS and our data, showing reduced amyloid burden and glial activation in the brains of 5XFAD transgenic mice, one may envision potential intervention with the progression of glial activation and AD by using AT1R blockers

Intranasal administration of telmisartan decreases amyloid plaques and CD11b staining in the cortex of 3-month-old 5XFAD mice.

<p>Mice were treated with telmisartan (Tel) or with vehicle (N,N-dimethylformamide/polyethylene glycol 400/saline (2:6:2) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155823#pone.0155823.ref047" target="_blank">47</a>]) for 3.5 weeks, and their brains were sectioned and immunolabeled with anti-Aβ (red) and anti-CD11b (green) antibodies and countersained with DAPI (blue). <b>(a, c)</b> Representative cortex brain section of WT or 5XFAD mice treated with 1 mg/kg/day telmisartan or with vehicle. Each experiment included 5 mice per group (n = 15 in total). (<b>b, d</b>) Quantification of the average sum of Aβ-stained area <b>(b)</b> and of CD11b-stained area <b>(d)</b>, represented as the mean ± SEM percentage of stained area in the corresponding vehicle-treated group, in at least 3 determinaions. Statistical significance was determined using one-way ANOVA, followed by a Tukey—Kramer Multiple Comparison Test. **P<0.01 vs. WT+Tel; ***P<0.001 vs. WT+Tel, ^^P<0.01 vs. 5XFAD+ vehicle; ^^^P<0.001 vs. 5XFAD + vehicle. <b>(e, f)</b> Representative hippocampal section of 5XFAD mice treated with vehicle. Scale bar is 200 μm.</p

Intranasal administration of telmisartan decreases amyloid plaques and CD11b staining in the cortex and hippocampus of 4-month old 5XFAD mice.

<p>Mice were treated with telmisartan (Tel) or vehicle (N,N-dimethylformamide/polyethylene glycol 400/saline (2:6:2) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155823#pone.0155823.ref047" target="_blank">47</a>]) for 8 weeks. The brains of 4-month-old mice were sectioned and immunolabeled with anti-Aβ (red) and anti-CD11b (green) antibodies and countersained with DAPI (blue). (<b>a, c</b>) Representative cortical sections from WT or 5XFAD mice treated with 1 mg/kg/day telmisartan or with vehicle. (<b>e, g</b>) Representative hippocampal sections of WT or 5XFAD mice treated with 1 mg/kg/day telmisartan or with vehicle. Each experiment included 6 mice per group (n = 18 in total). (<b>b, d, f, h</b>) Quantification of the average sum of Aβ-stained area <b>(b, f)</b> or of CD11b-stained area <b>(d, h)</b>, represented as the mean ± SEM percentage of stained area in the corresponding vehicle-treated group in at least 3 determinants. Statistical significance was determined using one-way ANOVA, followed by a Tukey—Kramer Multiple Comparison Test. ***P<0.001 vs. WT+Tel; ^^P<0.01 vs. 5XFAD+vehicle; ^^^P<0.001 vs. 5XFAD+vehicle. Scale bar is 200 μm.</p

Intranasal administration of perindopril decreases amyloid plaques and CD11b staining in the cortex of 3-month old 5XFAD mice.

<p>Mice were treated with perindopril or vehicle (saline) for 3.5 weeks. The brains of 3-month-old mice were sectioned and immunolabeled with anti-Aβ (red) and anti-CD11b (green) antibodies and countersained with DAPI (blue). <b>(a, c)</b> Representative brain section of WT or 5XFAD mice treated with 1 mg/kg/day perindopril or with vehicle. Each experiment included 5 mice per group (n = 15 in total). (<b>b, d)</b> Quantification of the average sum of Aβ-stained area <b>(b)</b> or of CD11b-stained area <b>(d)</b>, are represented as the mean ± SEM percentage of stained area in the corresponding vehicle-treated group in at least 3 determinants. Statistical significance was determined using one-way ANOVA, followed by a Tukey—Kramer Multiple Comparison Test. **P<0.01 vs. WT+perindopril; ***P<0.001 vs. WT+perindopril; ^^^P<0.001 vs. 5XFAD+vehicle. Scale bar is 200 μm.</p

Telmisartan decreased iNOS expression in LPS-induced BV2 microglia.

<p>Cells were incubated with LPS (7 ng/ml) in the presence or absence of telmisartan (Tel), at 1 μM or 5 μM, for 24h. 40 μg protein of whole cell lysate was loaded on 7.5% polyacrylamide-SDS gels. Analysis of iNOS was performed using antibodies against iNOS (130 kDa) and β-actin (40 kDa). Results are representative of two independent experiments and are presented as means ± SEM (overall n = 4–6). ***P<0.001 vs. control; ^^^P<0.001 vs. LPS.</p

Telmisartan decreased NO production in LPS-stimulated BV2 and primary neonatal rat glial cells.

<p>BV2 microglia <b>(a)</b>, primary microglial cells <b>(b)</b> and mixed glial cells <b>(C)</b> were incubated with LPS (7 ng/ml for BV2 cells and 0.5 μg/ml for primary cultures) in the presence or absence of telmisartan (Tel), at 1 μM or 5 μM, for 24h. NO levels were determined in the media and normalized to cells number. <i>Insets</i>: NO levels measured in non-stimulated cells treated with Tel at 1 μM or 5 μM concentrations. Data are presented as means ± SEM and are representatives of 2–3 independent experiments (overall n = 8–12). Statistical significance was determined using one-way ANOVA, followed by a Tukey—Kramer Multiple Comparison Test. ***P < 0.001 vs. control (non-stimulated cells); ^P < 0.05 vs. LPS; ^^^P < 0.001 vs. LPS; ^#P < 0.05 vs. LPS+Telmisartan 1μM; ^###P < 0.001 vs. LPS+Telmisartan 1μM; NS (non-significant) vs. control.</p

Telmisartan attenuated LPS-induced TNF-α and IL1-β release from BV2 microglia cells.

<p>Cells were incubated with LPS (7 ng/ml) in the presence or absence of telmisartan (Tel), at 1 μM or 5 μM, for 24h. Media were collected and analyzed for TNF-α and IL1-β levels and cells were counted. <i>Insets</i>: TNF-α and IL1-β levels measured in non-stimulated cells treated with Tel at 1 μM or 5 μM. Data presented as means ± SEM and are representatives of 2–3 independent experiments (overall n = 8–12). Statistical significance was determined using one-way ANOVA, followed by a Tukey—Kramer Multiple Comparison Test. ***P < 0.001 vs. control (non-stimulated cells); ^^^P < 0.001 vs. LPS; ^###P < 0.001 vs. LPS+Telmisartan 1μM; NS (non-significant) vs. control.</p