Chemokines in CNS injury and repair

Jaerve, Anne; Müller, Hans

doi:10.1007/s00441-012-1427-3

Cited by 137 publications

(92 citation statements)

References 206 publications

(217 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These chemokines are produced by several cell types, including endothelial cells, monocytes, astrocytes, and microglia, and their expression is known to be markedly upregulated in the mouse model of transient cerebral ischemia used here. 7,11,26 Our data confirm that plasma levels of CCL2/MCP-1 and CXCL2/MIP-2 remain increased by >25-fold at 24 hours and by >10-fold at 48 hours after cerebral ischemia-reperfusion in control mice and indicate that CBP treatment prevented these increases. These findings suggest that injection of this novel broad spectrum CBP after stroke can effectively target and remove multiple proinflammatory chemokines from the circulation.…”

Section: Discussionsupporting

confidence: 74%

Effect of a Broad-Specificity Chemokine-Binding Protein on Brain Leukocyte Infiltration and Infarct Development

Lee

Chu

Kim

et al. 2015

Stroke

View full text Add to dashboard Cite

Background and Purpose-Expression of numerous chemokine-related genes is increased in the brain after ischemicstroke. Here, we tested whether post-stroke administration of a chemokine-binding protein (CBP), derived from the parapoxvirus bovine papular stomatitis virus, might reduce infiltration of leukocytes into the brain and consequently limit infarct development. Methods-The binding spectrum of the CBP was evaluated in chemokine ELISAs, and binding affinity was determined using surface plasmon resonance. Focal stroke was induced in C57Bl/6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion for 23 or 47 hours. Mice were treated intravenously with either bovine serum albumin (10 μg) or CBP (10 μg) at the commencement of reperfusion. At 24 or 48 hours, we assessed plasma levels of the chemokines CCL2/MCP-1 and CXCL2/MIP-2, as well as neurological deficit, brain leukocyte infiltration, and infarct volume. Results-The CBP interacted with a broad spectrum of CC, CXC, and XC chemokines and bound CCL2/MCP-1 and CXCL2/MIP-2 with high affinity (pM range). Stroke markedly increased plasma levels of CCL2/MCP-1 and CXCL2/ MIP-2, as well as numbers of microglia and infiltrating leukocytes in the brain. Increases in plasma chemokines were blocked in mice treated with CBP, in which there was reduced neurological deficit, fewer brain-infiltrating leukocytes, and ≈50% smaller infarcts at 24 hours compared with bovine serum albumin-treated mice. However, CBP treatment was no longer protective at 48 hours. Conclusions-Post-stroke administration of CBP can reduce plasma chemokine levels in association with temporary attenuation of brain inflammation and infarct volume development.

show abstract

Section: Discussionsupporting

confidence: 74%

Effect of a Broad-Specificity Chemokine-Binding Protein on Brain Leukocyte Infiltration and Infarct Development

Lee

Chu

Kim

et al. 2015

Stroke

View full text Add to dashboard Cite

show abstract

“…Interestingly, MIP‐1α and MCP‐1 showed inverse patterns with regard to the clinical parameters: MIP‐1α was positively associated with disease duration and negatively related with DPR, whereas MCP‐1 exhibited a negative correlation with disease severity and was positively correlated with DPR, suggesting that MIP‐1α and MCP‐1 interact with different chemokine signal pathways in neuroinflammation. MCP‐1, which is also known as CCL2, is considered to be a proinflammatory chemokine and believed to exert a detrimental effect by activating the CCR2 receptor in the inflammatory process (Jaerve & Muller, 2012). Nevertheless, CCR1 and CCR5 are receptors of MIP‐1α, which differ from those of MCP‐1 and may explain the differential effects between MIP‐1α and MCP‐1, although the complex relationship between chemokine and receptor is still vague.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the levels of CSF and serum factors in ALS

et al. 2017

View full text Add to dashboard Cite

ObjectivesThe aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis.MethodsSerum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS‐r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study. Finally, we examined the correlations between factor levels and various clinical parameters and evaluated the predictive value for prognosis through a multivariate statistic model.ResultsA total of eight factors were obviously elevated in CSF, and twelve markers were increased in serum. In the correlation analyses, there were trends toward higher bFGF, VEGF, MIP‐1α levels in ALS with a longer disease duration and slower disease progression in both CSF and serum. Higher MCP‐1 levels were associated with worse disease severity and faster progression, and the IFN‐γ levels were positively associated with disease progression in either CSF or serum. Finally, a better prognosis was observed with higher levels bFGF in CSF and VEGF in CSF and serum; conversely, patients with higher levels of IFN‐γ in the CSF had shorter overall survival.ConclusionsWe demonstrated that a factor profile of ALS patients is distinct from control subjects and may be useful in clinical practice and therapeutic trials.

show abstract

“…The secondary damage initiates a series of degenerative events that results in further tissue destruction, massive cellular death, disrupted vasculature, increased permeability of the blood-spinal cord barrier, axonal demyelination, glial scar formation and neuroinflammation (Fehlings and Nguyen, 2010;Pajoohesh-Ganji and Byrnes, 2011;Jaerve and Muller, 2012). Because the secondary damage is so widespread, the prevention or a reduction in one or several of these secondary events post-SCI could potentially initiate spinal cord tissue repair and promote the overall improvement in functional outcomes.…”

Section: Resultsmentioning

confidence: 99%

Immune-Based Therapies for Spinal Cord Injury

Awad¹,

Gutierrez²,

Steinmetz³

2013

American Journal of Neuroscience

View full text Add to dashboard Cite

Traumatic Spinal Cord Injury (SCI) results in both focal and diffuse spinal cord pathologies that are exacerbated by an inflammatory response after the initial injury. Resident and infiltrating immune cells contribute significantly to the growth-refractory environment near the lesion and can intensify damage to spared tissue, resulting in impaired spontaneous functional recovery. Numerous studies have demonstrated that several immunomodulatory therapies administered after experimental SCI may be beneficial in promoting functional recovery. In this review, we focus on the therapeutic potential of the most abundant immune-based therapies e.g., rolipram, liposomal clodronate and TNF-α based therapy including etanercept, thalidomide and adenosine A1 receptor therapy their contribution to eliminating secondary damage and promoting recovery after SCI.

show abstract

Chemokines in CNS injury and repair

Cited by 137 publications

References 206 publications

Effect of a Broad-Specificity Chemokine-Binding Protein on Brain Leukocyte Infiltration and Infarct Development

Effect of a Broad-Specificity Chemokine-Binding Protein on Brain Leukocyte Infiltration and Infarct Development

Evaluating the levels of CSF and serum factors in ALS

Immune-Based Therapies for Spinal Cord Injury

Contact Info

Product

Resources

About