Monocyte chemoattractant protein-1 and the blood–brain barrier

Yao, Yao; Tsirka, Stella E.

doi:10.1007/s00018-013-1459-1

Cited by 149 publications

(134 citation statements)

References 283 publications

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“…We propose that because the MBs were confined within vessels in an intact BBB, the effect of pFUS on MB causes cavitation forces that would result in shockwaves (i.e., acoustic pressure waves into the parenchyma) (30) that activate microglia, astrocytes, and neurons beyond the vasculature. BBBD and changes in TJP expression represent one aspect of the effect of pFUS+MB that is associated with triggering the SIR, starting with increases in TNFα and other cytokines (49,50). Moreover, the increase in VEGF and MCP-1 and Ccl2 gene expression would contribute to BBBD and decrease TJP expression (50).…”

Section: Discussionmentioning

confidence: 99%

“…BBBD and changes in TJP expression represent one aspect of the effect of pFUS+MB that is associated with triggering the SIR, starting with increases in TNFα and other cytokines (49,50). Moreover, the increase in VEGF and MCP-1 and Ccl2 gene expression would contribute to BBBD and decrease TJP expression (50). Given the molecular responses that pFUS+MB induced in the brain, cavitation-induced shockwaves may cause cell membrane stretching or damage (51) that ultimately can induce CCTF and CAM expression.…”

Section: Discussionmentioning

confidence: 99%

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Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Kovács

Kim

Jikaria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

347

388

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MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NFκB pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL + neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68 + macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.pulsed focused ultrasound | microbubbles | blood-brain barrier | sterile inflammation | magnetic resonance imaging T he temporal proteomic profile in response to blood-brain barrier disruption (BBBD) consists of molecular features that are common across noninfectious insults such as ischemia, trauma, or autoimmune diseases (1-7). The main purpose of the bloodbrain barrier (BBB) is to maintain homeostasis, preventing the passive crossing of cells and molecules that could induce inflammation or damage to cells. The BBB consists of specialized endothelial cells connected through various tight junction proteins (TJP), astrocyte endplates, and a basement membrane. These components form part of the neurovascular unit (NVU) that is comprised of vessels, pericytes, microglia, astrocytes, and neurons along with the extracellular matrix (1,3,4,8). BBBD secondary to ischemia or trauma leads to increases in endothelial caveolae and down-regulation of TJP, transcytosis of plasma proteins (i.e., albumin), and vasogenic edema (1,6,(8)(9)(10)(11). The presence of albumin in the parenchyma following BBBD can activate astrocytes and microglia and induce the production of cytokines, chemokines, and trophic factors (CCTFs) and cell adhesion molecules (CAMs) as observed with a sterile inflammatory response (SIR) to injury (12-15). The release of CCTFs and inte...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Kovács

Kim

Jikaria

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

347

388

View full text Add to dashboard Cite

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“…On the other hand, increased CSF:albumin ratio may be driven by inflammatory mech anisms. 40 It is thus possible that the MMP/TIMP system has a role in inflammation-mediated tissue remodelling (i.e., reorganization of the extracellular matrix) in patients with bipolar disorder but that this process is obscured by the association between CSF levels of TIMPs and the CSF:serum albumin ratio.…”

Section: Discussionmentioning

confidence: 99%

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Jakobsson

Bjerke

Sahebi

et al. 2015

jpn

100

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“…However, we cannot exclude that peripheral (circulating) CCL2 is also involved. Peripherally produced CCL2 may cross the blood-brain barrier (BBB), possibly by interacting with specific carriers such as caveolin-1; in addition, CCL2 itself seems to affect BBB permeability (Yao and Tsirka, 2014), which is altered in the KA-lesioned hippocampus (Zattoni et al, 2011). Thus, we cannot rule out the possibility that LPS-induced CCL2 upregulation is a consequence of BBB disruption.…”

Section: Open Questionsmentioning

confidence: 97%

Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine

Bozzi

Caleo

2016

DNA and Cell Biology

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Epilepsy is a chronic disorder characterized by spontaneous recurrent seizures. Several lines of evidence demonstrate that inflammatory processes within the brain parenchyma contribute to recurrence and precipitation of seizures. In both epileptic patients and animal models, seizures upregulate inflammatory mediators, which in turn may enhance brain excitability. We recently showed that the C-C motif ligand 2 (CCL2) chemokine (also known as monocyte chemoattractant protein-1 [MCP-1]) mediates the seizure-promoting effects of inflammation. Systemic inflammatory challenge in chronically epileptic mice markedly enhanced seizure frequency and upregulated CCL2 expression in the brain. Selective pharmacological blockade of CCL2 synthesis or C-C chemokine receptor type 2 (CCR2) significantly suppressed inflammation-induced seizures. These results have important implications for the development of novel anticonvulsant therapies: drugs interfering with CCL2 signaling are used clinically for several human disorders and might be redirected for use in pharmacoresistant epilepsy. Here we review the role of CCL2/CCR2 signaling in linking systemic inflammation with seizure susceptibility and discuss some open questions that arise from our recent studies.

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Monocyte chemoattractant protein-1 and the blood–brain barrier

Cited by 149 publications

References 283 publications

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Disrupting the blood–brain barrier by focused ultrasound induces sterile inflammation

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Epilepsy, Seizures, and Inflammation: Role of the C-C Motif Ligand 2 Chemokine

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