The impact of microglial activation on blood-brain barrier in brain diseases

In the paper

“On the other hand, the endothelium can regulate the state of microglial activation.”

In the paper

“One of the key components of the cell death cascades in stroke is neuroinflammation, where the main players are microglial cells and the peripheral leukocytes, especially neutrophils and monocytes/macrophages.”

What the sources say

• Not checked yetcites Jin et al., 2010 source
• Not checked yetcites Enzmann et al., 2013 source
• Not checked yetcites Obermeier et al., 2013 source

In the paper

“Microglial and astrocytic IL-1β act directly on the endothelium, altering BBB permeability and contributing to epileptogenesis.”

What the sources say

• Not checked yetcites Ravizza et al., 2008a,b
• Not checked yetcites Morin-Brureau et al., 2011 source
• Not checked yetcites Librizzi et al., 2012 source

In the paper

“the authors suggest that microglia play a role in CNS angiogenesis by serving as a bridge to promote tip cell fusion, vascular plexus growth following sprouting induction and tip cell migration by VEGF (Fantin et al., 2010).”

What the sources say

• Not checked yetcites Fantin et al., 2010 source

In the paper

“The fact that microglia are present in the embryonic CNS territory prior to endothelial invasion and that they participate in cerebrovasculature growth place the interactions between microglia and CNS endothelium as a possible key mechanism in BBB formation and regulation.”

What the sources say

• Not checked yetcites Cuadros et al., 1993 source
• Not checked yetcites Fantin et al., 2010 source

In the paper

“Microglia become activated under brain injury and immunological stimuli (Kreutzberg, 1996) and undergo several alterations from a “resting state” to an active state (Hanisch and Kettenmann, 2007; Kettenmann et al., 2011).”

What the sources say

• Not checked yetcites Kreutzberg, 1996 source
• Not checked yetcites Hanisch and Kettenmann, 2007 source
• Not checked yetcites Kettenmann et al., 2011 source

In the paper

“In this phase, MMPs are important mediators: microglial ROS, especially superoxide radical O2−, increase vascular permeability also by stimulating MMP-2/MMP-3/MMP-9 production by microglia, astrocytes and ECs (Gottschall and Deb, 1996; Asahi et al., 2001; Rosenberg et al., 2001), contributing to hemorrhagic transformation and vasogenic edema.”

What the sources say

• Not checked yetcites Gottschall and Deb, 1996
• Not checked yetcites Asahi et al., 2001 source
• Not checked yetcites Rosenberg et al., 2001 source

In the paper

“After the ischemic insult, the recruitment of immune cells occurs in a biphasic dynamics. In the acute phase (within minutes), microglial cells are rapidly recruited to the injury site, due to the immediate release of cytokines and chemokines.”

What the sources say

• Not checked yetcites Kunsch and Medford, 1999
• Not checked yetcites Jin et al., 2010 source
• Not checked yetcites Enzmann et al., 2013 source

In the paper

“Blood-derived macrophages and microglia appear to have many functions in the dynamic process of CNS injury and repair, affecting BBB permeabilization, which in turn can aggravate stroke (Hallenbeck, 2002; Sandoval and Witt, 2008; Jiao et al., 2011).”

What the sources say

• Not checked yetcites Hallenbeck, 2002 source
• Not checked yetcites Sandoval and Witt, 2008
• Not checked yetcites Jiao et al., 2011 source

In the paper

“Some in vitro and in vivo studies have shown the role of IGF-1 in promoting neuroprotection and neuroregeneration (Li et al., 2010; Selvamani et al., 2012; Sohrabji and Williams, 2013; Bake et al., 2014).”

What the sources say

• Not checked yetcites Li et al., 2010
• Not checked yetcites Selvamani et al., 2012 source
• Not checked yetcites Sohrabji and Williams, 2013

In the paper

“In addition, ROS and NO can also reorganize the cytoskeleton of ECs and modulate tight junction proteins claudin-5 and occludin (Yamagata et al., 2004; Schreibelt et al., 2007) activate microglial cells; and up-regulate inflammatory mediators in the first 48 h.”

What the sources say

• Not checked yetcites Yamagata et al., 2004 source
• Not checked yetcites Schreibelt et al., 2007 source

In the paper

“These actions not only help enhancing the influx of peripheral leukocytes, but also contribute to the formation of vasogenic edema by allowing the diffusion of sodium and water (Sandoval and Witt, 2008).”

What the sources say

• Not checked yetcites Sandoval and Witt, 2008

In the paper

“Recently, the neuroinflammatory state was shown to activate the c-Jun N-terminal kinase (JNK) pathway not only in microglia but also in ECs, leading to microglial and endothelial activation with direct and microglial-induced BBB disruption, further cytokine production and perpetuation of the neuroinflammatory process (Tu et al., 2011; Wang et al., 2012).”

What the sources say

• Not checked yetcites Tu et al., 2011
• Not checked yetcites Wang et al., 2012 source

In the paper

“They activate the latent MMP-2 min after the ischemic insult, and are produced by microglia and astrocytes through the HIF-1α pathway (Yang and Rosenberg, 2011; Obermeier et al., 2013).”

What the sources say

• Not checked yetcites Yang and Rosenberg, 2011
• Not checked yetcites Obermeier et al., 2013 source

In the paper

“minocycline, a member of the tetracycline antibiotic family, inhibits activation of microglia and brain infiltrating blood-derived macrophages and protects cultured neurons from excitotoxic insults by preventing microglial generation of glutamate, IL-1β and NO (Yrjänheikki et al., 1998, 1999; Tikka et al., 2001).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Yrjänheikki et al., 1998, 1999
• Not checked yetcites Tikka et al., 2001 source

In the paper

“Inhibiting microglial activation may limit BBB disruption and reduce vasogenic edema in the context of ischemic stroke, reducing the volume of ischemic tissue and neuronal deficits, as well as preventing hemorrhagic transformation (Tikka et al., 2001; Yenari et al., 2006).”

What the sources say

• Not checked yetcites Tikka et al., 2001 source
• Not checked yetcites Yenari et al., 2006 source

In the paper

“These mediators also indirectly lead to BBB damage, by acting not on ECs, but on different components of the NVU: activating MMPs and acting on astrocytes and pericytes through ROS, NO and cytokines.”

In the paper

“In addition, ROS and NO can also reorganize the cytoskeleton of ECs and modulate tight junction proteins claudin-5 and occludin (Yamagata et al., 2004; Schreibelt et al., 2007) activate microglial cells; and up-regulate inflammatory mediators in the first 48 h.”

What the sources say

• Not checked yetcites Yamagata et al., 2004 source
• Not checked yetcites Schreibelt et al., 2007 source

In the paper

“These cells are activated, enhancing the release of ROS (through NADPH oxidase and MPO), cytokines (i.e., IL-1β, IL-6 and TNF-α) and chemokines (MCP-1, CXCL-1 and MIP-1α).”

What the sources say

• Not checked yetcites Kunsch and Medford, 1999
• Not checked yetcites Jin et al., 2010 source
• Not checked yetcites Enzmann et al., 2013 source

In the paper

“Also, very few infiltrating exogenous macrophages were observed over the first 72 h period and, instead, a profound increase in proliferating resident microglia cells was observed (Denes et al., 2007).”

What the sources say

• Not checked yetcites Denes et al., 2007 source

In the paper

“All these data suggest that microglia has a role in the EC damage and BBB disruption in stroke, making these cells a possible target to minimize the ischemic damage in stroke patients.”

In the paper

“Apart from the effects of MMPs, microglial-induced late-phase BBB disruption is due to direct effects on ECs: IL-1β and TNF-α downregulate tight junction proteins expression in ECs (Yamagata et al., 2004; Jiao et al., 2011) and, together with IL-6, modulate the expression of adhesion molecules (ICAM-1 and VCAM; Hallenbeck, 2002).”

What the sources say

• Not checked yetcites Yamagata et al., 2004 source
• Not checked yetcites Jiao et al., 2011 source
• Not checked yetcites Hallenbeck, 2002 source

In the paper

“MMPs are further stimulated by NK-κB and HIF-1α and disrupt TJ proteins (as ZO-1, claudin-5 and occludin), rendering the BBB leaky, downstream effects which were shown to be reverted by blocking NOS (Yang and Rosenberg, 2011; Gu et al., 2012; Obermeier et al., 2013).”

What the sources say

• Not checked yetcites Yang and Rosenberg, 2011
• Not checked yetcites Gu et al., 2012
• Not checked yetcites Obermeier et al., 2013 source

In the paper

“In AD, these cells can promote the clearance of Aβ, however, if they are not able to do that, there is an accumulation of Aβ deposits leading to neuronal death (Rogers et al., 2002).”

What the sources say

• Not checked yetcites Rogers et al., 2002 source

In the paper

“When activated, microglia impair BBB function through the release of several inflammatory modulators leading to a hyperpermeability condition, which is associated with several brain disorders.”

In the paper

“Multiple sclerosis is a chronic, progressive and neuroinflammatory demyelinating disease of the CNS, which involves an energy deficit, tissue remodeling, microglial activation and loss of BBB integrity (Lassmann et al., 2012).”

What the sources say

• Not checked yetcites Lassmann et al., 2012 source

In the paper

“it was observed in AD brains the presence of activated microglia and astrocytes around Aβ plaques, with the release of inflammatory cytokines, such as IL-1 and IL-6, TNF-α and transforming growth factor-β (TNF-β; Wyss-Coray, 2006; Zhou et al., 2012).”

What the sources say

• Not checked yetcites Wyss-Coray, 2006 source
• Not checked yetcites Zhou et al., 2012 source

In the paper

“Previous studies showed that systemic inflammation contributes to the disease progression and the activation of immune cells allows the infiltration of T and B cells into the CNS, promoting the release of chemokines that in turn stimulate the migration of more immune cells, leading to BBB disruption (Holman et al., 2011; Kooij et al., 2011; Larochelle et al., 2011; Willis, 2011).”

What the sources say

• Not checked yetcites Holman et al., 2011 source
• Not checked yetcites Kooij et al., 2011 source
• Not checked yetcites Larochelle et al., 2011 source

In the paper

“Moreover, high levels of Aβ are correlated with production of CCL2 by microglia, which leads to BBB impairment (Roberts et al., 2012).”

What the sources say

• Not checked yetcites Roberts et al., 2012 source

In the paper

“Hereupon, there are two different types of inflammation in MS. The first consists in the initial response to the disease, involving the infiltration of CD4+ and CD8+ T-cells and robust microglial activation; the second occurs due to the myelin destruction, stimulating the secondary recruitment of T cells, B cells and macrophages (Lassmann et al., 2012).”

What the sources say

• Not checked yetcites Lassmann et al., 2012 source

In the paper

“Furthermore, it was shown that intracranial injection of thrombin activates microglia, leading to the production of NO and TNFα via JAK2-STAT3 signaling pathway, which induce BBB disruption.”

What the sources say

• Not checked yetcites Huang et al., 2008a,b
• Not checked yetcites Yin et al., 2010 source
• Not checked yetcites Grammas, 2011 source

In the paper

“It has already been shown that the elimination of Aβ from the brain and the consequent impairment of microglial activation decrease ROS, nitrogen compounds and also inflammatory cytokines produced by microglial cells, which are correlated with the activation of ECs (Dickstein et al., 2006).”

What the sources say

• Not checked yetcites Dickstein et al., 2006 source

In the paper

“Moreover, during inflammation and demyelination in MS, the activation of microglial cells lead to the release of cytotoxic factors, such as NO and ROS, provoking myelin damage, release of proinflammatory cytokines (IFNγ, TNF-α and IL-1β), as well as chemokines (MCP-1), ultimately inducing BBB disruption (Mahad and Ransohoff, 2003).”

What the sources say

• Not checked yetcites Mahad and Ransohoff, 2003

In the paper

“Thus, regarding all evidences described above, we can hypothesize that microglia activation plays an important role during BBB disruption, which substantiates the need to study other factors correlated with inflammatory pathways, as potential targets of new strategies to reduce microglial-dependent inflammation in the brain of AD patients.”

In the paper

“The inhibition of microglial activation by minocycline favors the differentiation of oligodendrocyte precursors and immature oligodendrocytes. These cells are responsible for remyelination of neurons, an important event for improvement of MS condition (Li et al., 2005; Yenari et al., 2006; Defaux et al., 2011; Miron et al., 2013).”

What the sources say

• Not checked yetcites Li et al., 2005
• Not checked yetcites Yenari et al., 2006 source
• Not checked yetcites Defaux et al., 2011 source

In the paper

“Recently published data demonstrated that dipyridamole attenuates the expression of Toll-like receptor stimulation-dependent cytokines and chemokines in human microglia, reduces microglial activity in EAE mice, and consequently decreases IL-1β, TNF-α and IL-6 expression, which are responsible for increased BBB permeability (Sloka et al., 2013).”

What the sources say

• Not checked yetcites Sloka et al., 2013 source

In the paper

“experimental autoimmune encephalomyelitis (EAE), where activation of microglia precedes infiltration of peripheral macrophages and occurs before the onset of the disease (Sriram and Steiner, 2005).”

What the sources say

• Not checked yetcites Sriram and Steiner, 2005

In the paper

“Activated microglia are known to express ROS-generating enzymes, such as NADPH oxidase, which are responsible for degeneration of oligodendrocytes and increased BBB permeability by downregulating the expression of VE-cadherin, occludin and claudin-5 proteins in microvascular ECs (Fischer et al., 2012; Rochfort et al., 2014).”

What the sources say

• Not checked yetcites Fischer et al., 2012 source
• Not checked yetcites Rochfort et al., 2014 source

In the paper

“In this event, fibrinogen induces the activation of microglia and consequently the release of ROS, inducing axonal damage (Davalos et al., 2012).”

What the sources say

• Not checked yetcites Davalos et al., 2012 source

In the paper

“On the other hand, it has been shown that LPS induces the production of TNF-α in the brain by microglial cells, which promotes BBB dysfunction and also causes neuronal cell death by phagocytosis (Tanaka et al., 2006; Nishioku et al., 2010; Smith et al., 2012; Neniskyte et al., 2014).”

What the sources say

• Not checked yetcites Tanaka et al., 2006 source
• Not checked yetcites Nishioku et al., 2010 source
• Not checked yetcites Smith et al., 2012 source