G-CSF administration to adult mice stimulates the proliferation of microglia but does not modify the outcome of ischemic injury

Bartolini, Alice; Vigliani, Maria Claudia; Magrassi, Lorenzo; Vercelli, Alessandro; Rossi, Ferdinando

doi:10.1016/j.nbd.2010.11.013

Cited by 27 publications

(21 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shothat bone marrow-derived monocytes can infiltrate the retina and differentiate into cells with microglial phenotype. 17,36 Previous studies have also shown that microglia in the CNS 37,38 and the retina 39 can proliferate in situ under various pathologic conditions. The increased number of microglial-like cells in paraquat-treated mice could be attributed to immune cell infiltration and in situ proliferation.…”

Section: Discussionmentioning

confidence: 99%

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Chen

Luo²,

Peñalva³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE.To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation. RESULTS. Intravitreal injection of paraquat (0.75 lM) resulted in acute retinal capillary nonperfusion within 2 days, which improved from 4 days to 4 weeks postinjection (p.i.). Panretinal degeneration was observed at 4 days p.i. and progressed further at 4 weeks p.i. In the absence of CX3CR1, retinal degeneration was exaggerated and was accompanied by increased TNF-a, iNOS, IL-1b, Ccl2, and Casp-1 gene expression. Confocal microscopy of retinal flatmounts revealed microglial activation and CD44 þ MHC-II þ monocyte and GR1 þ neutrophil infiltration in paraquat-injected eyes. The number of activated microglia and infiltrating leukocytes was significantly higher in CX3CR1 gfp/gfp mice than in CX3CR1 gfp/þ mice. CONCLUSIONS.Our results suggest that the CX3CR1 signaling pathway may play an important role in controlling retinal inflammation under oxidative and ischemia/reperfusion conditions. In the absence of CX3CR1, uncontrolled retinal inflammation results in exaggerated retinal degeneration. (Invest Ophthalmol Vis Sci. 2013;54:682-690)

show abstract

Section: Discussionmentioning

confidence: 99%

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Chen

Luo²,

Peñalva³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…A possible mechanism for this phenomenon is that G-CSF enhances an inflammatory response after stroke [17,29]. Stroke generally disturbs the integrity of the blood-brain barrier, which permits input of inflammatory cells into brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies to endothelial nitric oxide synthase (eNOS), its phosphorylated form (phospho-eNOS) and PECAM-1(CD31) were applied to evaluate the degree of angiogenesis, while that to Akt, its phosphorylated form (phospho-Akt) and caspase-3 to observe cell survival and apoptosis [14][15][16]. Antibody to Iba1, microglial marker, was treated to evaluate intracerebral inflammation [17].…”

Section: Western Blot Analysismentioning

confidence: 99%

Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats

et al. 2014

View full text Add to dashboard Cite

We investigated the additive effect of repetitive transcranial magnetic stimulation (rTMS) combined with granulocyte-colony stimulating factor (G-CSF) on functional outcome in the early subacute phase of stroke. Seven-week-old male rats were subjected to permanent middle cerebral artery occlusion (MCAo) and were divided into four groups: normal saline administration with sham rTMS (group 1, n = 15), G-CSF administration with sham rTMS (group 2, n = 15), G-CSF with 1 Hz rTMS (group 3, n = 14), and G-CSF with 20 Hz rTMS (group 4, n = 15). Animals received G-CSF or saline for 5 days from the day of MCAo and were concurrently treated with 20-min rTMS on their lesioned hemisphere for 2 weeks. Neurological functional score was worse in group 4 compared to that in group 2 on day 15. In Western blots conducted on day 25, phosphorylation of endothelial nitric oxide synthase was markedly lower in groups 2, 3, and 4 than that in group 1 in the ischemic border zone. PECAM-1 expression at ischemic core was lower in groups 4 than in group 2. Caspase-3 expression was markedly higher in groups 4 than in group 1, 2, 3 at ischemic core. Iba1 expression was higher in groups 4 than in group 1, 2 at ischemic core. G-CSF combined with rTMS administered in the early subacute phase of ischemic stroke may exert a hazardous effect on functional recovery, possibly due to impaired angiogenic mechanism, decreased cell survival, and increased inflammation.

show abstract

“…Considering these mediators have been suggested to contribute to ischemic brain injury [49,50,51,52], it is possible that these cytokines contribute to whatever cell death was evident at this dose. However, treatment with or secretion of these chemokines promotes the proliferation, migration and activation of more microglial and other cells [53,54,55], which in turn would provide support for the containment and resolution of injury. There is also increasing evidence now to show that chemokines such as MCP-1, MIP-1a, MIP-1b, RANTES, GCSF, GMCSF and MIP-2 are also involved in neuroprotection-regeneration [56,57,58,59,60].…”

Section: Discussionmentioning

confidence: 99%

Phenotype and Secretory Responses to Oxidative Stress in Microglia

Pathipati

Müller²,

Jiang

et al. 2013

Dev Neurosci

View full text Add to dashboard Cite

The neonatal brain is particularly susceptible to oxidative stress. Our group has previously shown that following hypoxic-ischemic injury, hydrogen peroxide (H₂O₂) levels rise significantly particularly in the neonatal brain and are sustained for up to 7 days. This rapidly accumulated H₂O₂ is detrimental in the iron-rich immature brain as it can lead to the generation of dangerous free radicals that can cause extensive injury. To date, there is limited literature on the effects of increased H₂O₂ levels on microglial cells, which have been extensively implicated in the ensuing inflammatory injury. Microglial cultures were derived from the P1 mouse brain and exposed to either bolus concentrations of H₂O₂ (15 or 50 μM) or varying concentrations of continuous exposure for 4, 18 or 24 h. Continuous exposure of microglia to H₂O₂ was generated using the glucose oxidase-catalase system generating levels of H₂O₂ <10 μM. Reactive oxygen species and nitric oxide expression were measured. Conditioned medium was collected and analyzed for secreted cytokine levels. Treated cell extracts were processed for glutathione (oxidized and reduced) content and fixed cells were labeled for M1 and M2a phenotype markers. Overall, it is evident that microglial exposure to continuous H₂O₂ has pleiotropic and biphasic effects. Continuous exposure to very low levels of H₂O₂ is more damaging to cell survival than higher bolus doses at 18 h, and can produce considerably high levels of pro- and anti-inflammatory cytokines by 18 h. Significantly high levels of various chemokines/chemotactic molecules such as G-CSF, MIP-1b and MIP-2 are also produced in response to continuous low-dose H₂O₂ by 18 h. Interestingly, no prominent cytokine responses were seen with bolus treatment at any of the time points studied. H₂O₂ exposure promotes an M2a microglial phenotype in the absence of IL-4/IL-13 signaling, suggesting a wound-healing role for microglia and a delayed activation mechanism for H₂O₂ after such an insult. Together, these specific effects can be used to clarify the microglial cell responses following injury in the immature brain.

show abstract

G-CSF administration to adult mice stimulates the proliferation of microglia but does not modify the outcome of ischemic injury

Cited by 27 publications

References 51 publications

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation

Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats

Phenotype and Secretory Responses to Oxidative Stress in Microglia

Contact Info

Product

Resources

About