MCP-1 induces migration of adult neural stem cells

Widera, Darius; Holtkamp, Wolf; Entschladen, Frank; Niggemann, Bernd; Zänker, Kurt S.; Kaltschmidt, Barbara; Kaltschmidt, Christian

doi:10.1078/0171-9335-00403

Cited by 177 publications

(141 citation statements)

References 26 publications

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“…One would predict from this observation that several different chemokines might act as chemoattractants for these cells, and indeed, this is the case. Our studies, as well as others, have demonstrated that many chemokines can act as chemoattractants for neural progenitor cells cultured as neurospheres (Widera et al, 2004;Tran et al, unpublished observations). Moreover, it is not just cultured progenitors that express these receptors.…”

Section: Chemokines and Adult Neurogenesissupporting

confidence: 78%

HIV-1, chemokines and neurogenesis

Tran

Miller

2005

neurotox res

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HIV-1 infection of the brain results in a large number of behavioural defecits accompanied by diverse neuropathological signs. However,it is not clear how the virus produces these effects or exactly how the neuropathology and behavioural defecits are related. In this article we discuss the possibility that HIV-1 infection may negatively impact the process of neurogenesis in the adult brain and that this may contribute to HIV-1 related effects on the nervous system. We have previously demonstrated that the development of the dentate gyrus during embryogenesis requires signaling by the chemokine SDF-1 via its receptor CXCR4. We demonstrated that neural progenitor cells that give rise to dentate granule neurons express CXCR4 and other chemokine receptors and migrate into the nascent dentate gyrus along SDF-1 gradients.

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Section: Chemokines and Adult Neurogenesissupporting

confidence: 78%

HIV-1, chemokines and neurogenesis

Tran

Miller

2005

neurotox res

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“…We have shown before that MMP‐9 and MCP‐1 are reduced in ischemic stroke with post‐stroke BML‐111 administration (Hawkins et al., 2014). These factors are important in neural stem cell proliferation and migration during neurogenesis after ischemic stroke (Lee et al., 2006; L. Wang et al., 2006; Widera et al., 2004; Yan et al., 2007). Additionally, MMP‐9 is important in vascular remodeling after stroke and inhibiting MMP‐9 1 week after stroke increases infarct size and worsens outcomes (Zhao et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

et al. 2017

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BackgroundResolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti‐inflammatory, pro‐resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML‐111. We hypothesized that post‐ischemic, intravenous treatment with BML‐111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML‐111 on the post‐stroke molecular and cellular profile.MethodsA total of 133 male Sprague‐Dawley rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and BML‐111 administration was started at the time of reperfusion. Two methods of week‐long BML‐111 intravenous administration were tested: continuous infusion via ALZET ® osmotic pumps (1.25 and 3.75 μg μl−1 hr−1), or freshly prepared daily single injections (0.3, 1, and 3 mg/kg). We report for the first time on the stability of BML‐111 and characterized an optimal dose and a dosing schedule for the administration of BML‐111.ResultsOne week of BML‐111 intravenous injections did not reduce infarct size or improve behavioral deficits 4 weeks after ischemic stroke. However, post‐ischemic treatment with BML‐111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1 week after stroke. This protection was associated with reduced pro‐inflammatory cytokine and chemokine levels, decreased M1 CD40+ macrophages, and increased alternatively activated, anti‐inflammatory M2 microglia/macrophage cell populations in the post‐ischemic brain.ConclusionThese data suggest that targeting the endogenous LXA 4 pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA 4 analogs could confer long‐term protection.

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“…In the nervous system, SDF-1/CXCR4 signaling directs the migration of neural stem cells to a number of different parts of the brain (Zou et al, 1998;Bagri et al, 2002;Lu et al, 2002;Stumm et al, 2003) and the DRG (Belmadani et al, 2005) and also plays a role as an axonal guidance cue (Xiang et al, 2002;Arakawa et al, 2003;Chalasani et al, 2003;Lieberam et al, 2005;Pujol et al, 2005). It has also been demonstrated that neurospheres prepared from postnatal brains express CXCR4 as well as other chemokine receptors (Lazarini et al, 2000;Stumm et al, 2003;Ji et al, 2004;Peng et al, 2004;Tran et al, 2004) and that chemokines act as chemoattractants for these cells (Pluchino et al, 2005;Tran et al, 2004Tran et al, , 2005Widera et al, 2004), suggesting that chemokine-mediated effects may also be important in the regulation of adult progenitor cell migration. However, it is not known whether chemokine receptors are normally expressed by neural progenitor cells in the postnatal brain.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have indicated that neural progenitors cultured from postnatal brains expressed numerous chemokine receptors, in addition to CXCR4 (Ji et al, 2004;Krathwohl and Kaiser, 2004;Tran et al, 2004;Widera et al, 2004). This might allow neural progenitors to respond to different chemokines upregulated in the context of neuroinflammation in the brain.…”

Section: Expression Of Chemokine Receptors In Neurogenic Areas Of Moumentioning

confidence: 99%

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

Tran

Banisadr

Ren

et al. 2006

J of Comparative Neurology

219

228

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We previously demonstrated that chemokine receptors are expressed by neural progenitors grown as cultured neurospheres. To examine the significance of these findings for neural progenitor function in vivo, we investigated whether chemokine receptors were expressed by cells having the characteristics of neural progenitors in neurogenic regions of the postnatal brain. Using in situ hybridization we demonstrated the expression of CCR1, CCR2, CCR5, CXCR3, and CXCR4 chemokine receptors by cells in the dentate gyrus (DG), subventricular zone of the lateral ventricle, and olfactory bulb. The pattern of expression for all of these receptors was similar, including regions where neural progenitors normally reside. In addition, we attempted to colocalize chemokine receptors with markers for neural progenitors. In order to do this we used nestin-EGFP and TLXLacZ transgenic mice, as well as labeling for Ki67, a marker for dividing cells. In all three areas of the brain we demonstrated colocalization of chemokine receptors with these three markers in populations of cells. Expression of chemokine receptors by neural progenitors was further confirmed using CXCR4-EGFP BAC transgenic mice. Expression of CXCR4 in the DG included cells that expressed nestin and GFAP as well as cells that appeared to be immature granule neurons expressing PSA-NCAM, calretinin, and Prox-1. CXCR4-expressing cells in the DG were found in close proximity to immature granule neurons that expressed the chemokine SDF-1/CXCL12. Cells expressing CXCR4 frequently coexpressed CCR2 receptors. These data support the hypothesis that chemokine receptors are important in regulating the migration of progenitor cells in postnatal brain. Indexing terms stem cells; development; chemotaxis; brain repairDuring embryogenesis, neural stem/progenitor cells must migrate long distances from the germinal epithelia where they are born to their final destinations (Hatten, 1999;Alvarez-Buylla et al., 2001). During migration, stem cells may continue to divide and also become restricted in terms of their ultimate phenotypes. Thus, the timing of neuro-and gliogenesis in the developing embryo is precisely controlled (Rallu et al., 2002). The factors that determine the migration, proliferation, and differentiation of embryonic stem cells have been widely investigated and numerous factors have been shown to influence these processes (Lindvall et al., 2004). One group of molecules that has recently been shown to control progenitor cell migration in the nervous system are the chemokines (CHEMO-tactic cytoKINES) (Tran and © NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript Miller, 2003). The chemokines are a family of small secreted proteins that are known to be important regulators of leukocyte trafficking under both normal conditions and during inflammatory responses (Moser et al., 2004). Furthermore, it is now known that chemokine signaling has an important role to play in the developing embryo. Deletion of the genes for the CXCR4 chemokine receptor or f...

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MCP-1 induces migration of adult neural stem cells

Cited by 177 publications

References 26 publications

HIV-1, chemokines and neurogenesis

HIV-1, chemokines and neurogenesis

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

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MCP-1 induces migration of adult neural stem cells

Cited by 177 publications

References 26 publications

HIV-1, chemokines and neurogenesis

HIV-1, chemokines and neurogenesis

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: Protective mechanisms and long‐term effects on neurological recovery

Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain

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Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery