CXCL12/CXCR4/CXCR7 Chemokine Axis in the Central Nervous System Therapeutic Targets for Remyelination in Demyelinating Diseases

I still don't know if stroke causes demyelination. Ask your doctor and if it does, What stroke protocols are there to remyelinate?

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Tianci Chu, Lisa B. E. Shields, Yi Ping Zhang, Shi-Qing Feng, Christopher B. Shields, Jun Cai

First Published January 10, 2017 review-article

Abstract

The chemokine CXCL12 plays a vital role in regulating the development of the central nervous system (CNS) by binding to its receptors CXCR4 and CXCR7. Recent studies reported that the CXCL12/CXCR4/CXCR7 axis regulates both embryonic and adult oligodendrocyte precursor cells (OPCs) in their proliferation, migration, and differentiation. The changes in the expression and distribution of CXCL12 and its receptors are tightly associated with the pathological process of demyelination in multiple sclerosis (MS), suggesting that modulating the CXCL12/CXCR4/CXCR7 axis may benefit myelin repair by enhancing OPC recruitment and differentiation. This review aims to integrate the current findings of the CXCL12/CXCR4/CXCR7 signaling pathway in the CNS and to highlight its role in oligodendrocyte development and demyelinating diseases. Furthermore, this review provides potential therapeutic strategies for myelin repair by analyzing the relevance between the pathological changes and the regulatory roles of CXCL12/CXCR4/CXCR7 during MS.

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The migration and differentiation of hUC-MSCsCXCR4/GFP encapsulated in BDNF/chitosan scaffolds for brain tissue engineering

This explains one of the problems of stem cells for the brain.
http://www.ingentaconnect.com/content/iop/biomed/2016/00000011/00000003/art035004

Authors: Huang, Chuanjun; Zhao, Longxiang; Gu, Jun; Nie, Dekang; Chen, Yinan; Zuo, Hao; Huan, Wei; Shi, Jinlong; Chen, Jian; Shi, Wei

Source: Biomedical Materials, Volume 11, Number 3, June 2016, pp. 35004-35012(9)
Publisher: IOP Publishing

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Abstract:

We previously developed a biomaterial scaffold that could effectively provide seed cells to a lesion cavity resulting from traumatic brain injury. However, we subsequently found that few transplanted human umbilical cord mesenchymal stem cells (hUC-MSCs) are able to migrate from the scaffold to the lesion boundary. Stromal derived-cell factor-1α and its receptor chemokine (C-X-C motif) receptor (CXCR)4 are chemotactic factors that control cell migration and stem cell recruitment to target areas. Given the low expression level of CXCR4 on the hUC-MSC membrane, lentiviral vectors were used to generate hUC-MSCs stably expressing CXCR4 fused to green fluorescent protein (GFP) (hUC-MSCs^CXCR4/GFP). We constructed a scaffold in which recombinant human brain-derived neurotrophic factor (BDNF) was linked to chitosan scaffolds with the crosslinking agent genipin (CGB scaffold). The scaffold containing hUC-MSCs^CXCR4/GFP was transplanted into the lesion cavity of a rat brain, providing exogenous hUC-MSCs to both lesion boundary and cavity. These results demonstrate a novel strategy for inducing tissue regeneration after traumatic brain injury.

Document Type: Research Article
DOI: http://dx.doi.org/10.1088/1748-6041/11/3/035004

CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells

I didn't understand so ask your doctor to translate and put into a useful stroke protocol. Unless you ask, nothing is going to get done. 

CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells

Abstract

Neural stem/progenitor cells (NSC) respond to injury after brain injuries secreting IL-1, IL-6, TNF-α, IL-4 and IL-10, as well as chemokines members of the CC and CXC ligand families. CXCL12 is one of the chemokines secreted at an injury site and is known to attract NSC-derived neuroblasts, cells that express CXCL12 receptor, CXCR4. Activation of CXCR4 by CXCL12 depends on two domains located at the N-terminal of the chemokine. In the present work we aimed to investigate if the N-terminal end of CXCL12, where CXCR4 binding and activation domains are located, was sufficient to induce NSC-derived neuroblast chemotaxis. Our data show that a synthetic peptide analogous to the first 21 amino acids of the N-terminal end of CXCL12, named PepC-C (KPVSLSYRCPCRFFESHIARA), is able to promote chemotaxis of neuroblasts in vivo, and stimulate chemotaxis and proliferation of CXCR4 + cells in vitro, without affecting NSC fate. We also show that PepC-C upregulates CXCL12 expression in vivo and in vitro. We suggest the N-terminal end of CXCL12 is responsible for a positive feedback loop to maintain a gradient of CXCL12 that attracts neuroblasts from the subventricular zone into an injury site.

Current status of chemokines in the adult CNS

Your doctor won't know about this so ask.
http://www.sciencedirect.com/science/article/pii/S0301008213000099

Abstract

Chemokines – chemotactic cytokines – are small secreted proteins that attract and activate immune and non-immune cells in vitro and in vivo. It has been suggested that chemokines and their receptors play a role in the central nervous system (CNS), in addition to their well established role in the immune system. We focus here on three chemokines—CXCL12 (C-X-C motif ligand 12), CCL2 (C-C motif ligand 2), and CX3CL1 (C-X-3C motif ligand 1) – and their principal receptors – CXCR4 (C-X-C motif receptor 4), CCR2 (C-C motif receptor 2) and CX3CR1 (C-X-3C motif receptor 1), respectively. We first introduce the classification of chemokines and their G-protein coupled receptors and the main signaling pathways triggered by receptor activation. We then discuss the cellular distribution of CXCL12/CXCR4, CCL2/CCR2 and CX3CL1/CX3CR1 in adult brain and the neurotransmission and neuromodulation effects controlled by these chemokines in the adult CNS. Changes in the expression of CXCL12, CCL2 and CX3CL1 and their respective receptors are also increasingly being implicated in the pathogenesis of CNS disorders, such as Alzheimer's disease, Parkinson's disease, HIV-associated encephalopathy, stroke and multiple sclerosis, and are therefore plausible targets for future pharmacological intervention. The final section thus discusses the role of these chemokines in these pathophysiological states. In conclusion, the role of these chemokines in cellular communication may make it possible: (i) to identify new pathways of neuron–neuron, glia–glia or neuron–glia communications relevant to both normal brain function and neuroinflammatory and neurodegenerative diseases; (ii) to develop new therapeutic approaches for currently untreatable brain diseases.