Heterozygous Deletion of EphrinA5 Does Not Improve Functional Recovery After Experimental Stroke

Completely and totally useless for survivors. Not even an abstract to get a clue of what it is about. A great stroke association would make all stroke research freely available to all survivors. 

Heterozygous Deletion of EphrinA5 Does Not Improve Functional Recovery After Experimental Stroke

EphrinB2 activation enhances angiogenesis, reduces amyloid-β deposits and secondary damage in thalamus at the early stage after cortical infarction in hypertensive rats

WHOM will follow this up with research in humans?  It won't occur in your lifetime since we have NO stroke leadership driving results and following a strategy to its logical conclusion. 100% recovery for all. 

EphrinB2 activation enhances angiogenesis, reduces amyloid-β deposits and secondary damage in thalamus at the early stage after cortical infarction in hypertensive rats 

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Shihui Xing¹

Shihui Xing

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Nannan Pan²

Nannan Pan

2Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China
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, Wei Xu¹

Wei Xu

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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Jian Zhang¹

Jian Zhang

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Jingjing Li¹

Jingjing Li

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Chao Dang¹

Chao Dang

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Gang Liu¹

Gang Liu

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Zhong Pei¹

Zhong Pei

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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, Jinsheng Zeng¹

Jinsheng Zeng

1Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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...

First Published April 6, 2018 Research Article

https://doi.org/10.1177/0271678X18769188

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Article Information

Article first published online: April 6, 2018
Received: November 04, 2017; Accepted: March 14, 2018

https://doi.org/10.1177/0271678X18769188

Shihui Xing¹, Nannan Pan², Wei Xu¹, Jian Zhang¹, Jingjing Li¹, Chao Dang¹, Gang Liu¹, Zhong Pei¹, Jinsheng Zeng¹

¹Department of Neurology and Stroke Center, 71068The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

²Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China

Corresponding Author: Shihui Xing and Jinsheng Zeng, Stroke Center and Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China. Email: xingshih@mail.sysu.edu.cn; zengjs@pub.guangzhou.gd.cn

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Abstract

Cerebral infarction causes secondary neurodegeneration and angiogenesis in thalamus, which impacts functional recovery after stroke. Here, we hypothesize that activation of ephrinB2 could stimulate angiogenesis and restore the secondary neurodegeneration in thalamus after cerebral infarction. Focal cerebral infarction was induced by middle cerebral artery occlusion (MCAO). Secondary damage, angiogenesis, amyloid-β (Aβ) deposits, levels of ephrinB2 and receptor for advanced glycation end product (RAGE) in the ipsilateral thalamus were determined by immunofluorescence and immunoblot. The contribution of ephrinB2 to angiogenesis was determined by siRNA-mediated knockdown of ephrinB2 and pharmacological activation of ephrinB2. The results showed that formation of new vessels and ephrinB2 expression was markedly increased in the ipsilateral thalamus at seven days after MCAO. EphrinB2 knockdown markedly suppressed angiogenesis coinciding with increased Aβ accumulation, neuronal loss and gliosis in the ipsilateral thalamus. In contrast, clustered EphB2-Fc significantly enhanced angiogenesis, alleviated Aβ accumulation and the secondary thalamic damage, which was accompanied by accelerated function recovery. Additionally, activation of ephrinB2 significantly reduced RAGE levels in the ipsilateral thalamus. Our findings suggest that activation of ephrinB2 promotes angiogenesis, ameliorates Aβ accumulation and the secondary thalamic damage after cerebral infarction. Additionally, RAGE might be involved in Aβ clearance by activating ephrinB2 in the thalamus.

Astrocytic Ephrin-B1 Regulates Synapse Remodeling Following Traumatic Brain Injury

This sounds like it might be useful for us also. But there is no one in the world we can ask if this might be useful because there is NO leadership and NO strategy in the stroke world. 

Astrocytic Ephrin-B1 Regulates Synapse Remodeling Following Traumatic Brain Injury

1. Angeliki M. Nikolakopoulou1
2. Jordan Koeppen1,2
3. Michael Garcia1
4. Joshua Leish1
5. Andre Obenaus3
6. Iryna M. Ethell1,2⇑

1. ¹Biomedical Sciences Division, School of Medicine, University of California Riverside, CA, USA
2. ²Cell, Molecular, and Developmental Biology graduate program, University of California Riverside, CA, USA
3. ³Department of Pediatrics, School of Medicine, Loma Linda University, CA, USA

1. Iryna M. Ethell, Biomedical Sciences Division, School of Medicine, University of California, 900 University Avenue, Riverside, CA 92521, USA. Email: iryna.ethell@ucr.edu

Abstract

Traumatic brain injury (TBI) can result in tissue alterations distant from the site of the initial injury, which can trigger pathological changes within hippocampal circuits and are thought to contribute to long-term cognitive and neuropsychological impairments. However, our understanding of secondary injury mechanisms is limited. Astrocytes play an important role in brain repair after injury and astrocyte-mediated mechanisms that are implicated in synapse development are likely important in injury-induced synapse remodeling. Our studies suggest a new role of ephrin-B1, which is known to regulate synapse development in neurons, in astrocyte-mediated synapse remodeling following TBI. Indeed, we observed a transient upregulation of ephrin-B1 immunoreactivity in hippocampal astrocytes following moderate controlled cortical impact model of TBI. The upregulation of ephrin-B1 levels in hippocampal astrocytes coincided with a decline in the number of vGlut1-positive glutamatergic input to CA1 neurons at 3 days post injury even in the absence of hippocampal neuron loss. In contrast, tamoxifen-induced ablation of ephrin-B1 from adult astrocytes in ephrin-B1^loxP/yERT2-Cre^GFAP mice accelerated the recovery of vGlut1-positive glutamatergic input to CA1 neurons after TBI. Finally, our studies suggest that astrocytic ephrin-B1 may play an active role in injury-induced synapse remodeling through the activation of STAT3-mediated signaling in astrocytes. TBI-induced upregulation of STAT3 phosphorylation within the hippocampus was suppressed by astrocyte-specific ablation of ephrin-B1 in vivo, whereas the activation of ephrin-B1 in astrocytes triggered an increase in STAT3 phosphorylation in vitro. Thus, regulation of ephrin-B1 signaling in astrocytes may provide new therapeutic opportunities to aid functional recovery after TBI.

Molecular Control of Axon Branching

We need this so ask your doctor for how to do this to help your recovery. That's after they explain the damage to your white matter. 

Molecular Control of Axon Branching

Abstract

Axon branching is a complex morphological process, the regulation of which we are just beginning to understand. Many factors known to be important for axon growth and guidance have emerged as key regulators of axon branching. The extrinsic factors implicated in axon branching include traditional axon guidance cues such as the slits, semaphorins, and ephrins; neurotrophins such as BDNF; the secreted glycoprotein Wnt; the extracellular matrix protein anosmin-1; and certain transmembrane cell adhesion molecules—as well as sensory experience and neuronal activity. Although less is known about the intracellular control of axon branching, in recent years significant advances have been made in this area. Kinases and their regulators, Rho GTPases and their regulators, transcription factors, ubiquitin ligases, and several microtubule and actin-binding proteins are now implicated in the control of axon branching. It is likely that many more branching regulators remain to be discovered, as do the links between extrinsic cues and intracellular signaling proteins in the control of axon branching.

Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling

Ask your doctor how you can use this in your rehab. 

Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling

Abstract

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Neurogenesis in the adult hippocampus involves activation of quiescent neural stem cells (NSCs) to yield transiently amplifying NSCs, progenitors, and, ultimately, neurons that affect learning and memory. This process is tightly controlled by microenvironmental cues, although a few endogenous factors are known to regulate neuronal differentiation. Astrocytes have been implicated, but their role in juxtacrine (that is, cell-cell contact dependent) signaling in NSC niches has not been investigated. We found that ephrin-B2 presented from rodent hippocampal astrocytes regulated neurogenesis in vivo. Furthermore, clonal analysis in NSC fate-mapping studies revealed a previously unknown role for ephrin-B2 in instructing neuronal differentiation. In addition, ephrin-B2 signaling, transduced by EphB4 receptors on NSCs, activated β-catenin in vitro and in vivo independently of Wnt signaling and upregulated proneural transcription factors. Ephrin-B2⁺ astrocytes therefore promote neuronal differentiation of adult NSCs through juxtacrine signaling, findings that advance our understanding of adult neurogenesis and may have future regenerative medicine implications.

Molecule found that inhibits recovery from stroke

So lets get some more research into how to develop a therapy protocol for this. 

Molecule found that inhibits recovery from stroke

FINDINGS:
Researchers at UCLA have identified a novel molecule in the brain that, after stroke, blocks the formation of new connections between neurons. As a result, it limits the brain's recovery. In a mouse model, the researchers showed that blocking this molecule—called ephrin-A5--induces axonal sprouting, that is, the growth of new connections between the brain's neurons, or cells, and as a result promotes functional recovery.

IMPACT:
If duplicated in humans, the identification of this molecule could pave the way for a more rapid recovery from stroke and may allow a synergy with existing treatments, such as physical therapy.

UCLA AUTHOR:
Dr. S. Thomas Carmichael, professor of neurology, and colleagues

JOURNAL:
The research appears online this week in the journal PNAS.

MORE:
Stroke is the leading cause of adult disability because of the brain's limited capacity for repair. An important process in recovery after stroke may be in the formation of new connections, termed axonal sprouting. The adult brain inhibits axonal sprouting and the formation of these connections. In previous work the researchers found, paradoxically, that the brain sends mixed signals after a stroke—activating molecules that both stimulate and inhibit axonal sprouting. In this present work, the researchers have identified the effect of one molecule that inhibits axonal sprouting and determined the new connections in the brain that are necessary to form for recovery.
The researchers also developed a new tissue bioengineering approach for delivering drugs to the brain after stroke. This approach uses a biopolymer hydrogel, or a gel of naturally occurring brain proteins, to release neural repair molecules directly to the target region for recovery in stroke—the tissue adjacent to the center of the stroke.
Last, the paper also shows that the more behavioral activity after stroke, such as the amount an impaired limb is used, the more new connections are directly stimulated to form in the injured brain. This direct link between movement patterns, like those that occur in neurorehabilitation, and the formation of new brain connections, provides a biological mechanism for the effects of some forms of physical therapy after stroke.

Ephrin-A1-Mediated Dopaminergic Neurogenesis and Angiogenesis in a Rat Model of Parkinson's Disease

I know this is for Parkinsons but it does have some interesting possibilities in migration and signalling. 

Ephrin-A1-Mediated Dopaminergic Neurogenesis and Angiogenesis in a Rat Model of Parkinson's Disease

Abstract Top

Cells of the neural stem cell lineage in the adult subventricular zone (SVZ) respond to brain insult by increasing their numbers and migrating through the rostral migratory stream. However, in most areas of the brain other than the SVZ and the subgranular zone of the dentate gyrus, such a regenerative response is extremely weak. Even these two neurogenic regions do not show extensive regenerative responses to repair tissue damage, suggesting the presence of an intrinsic inhibitory microenvironment (niche) for stem cells. In the present study, we assessed the effects of injection of clustered ephrin-A1-Fc into the lateral ventricle of rats with unilateral nigrostriatal dopamine depletion. Ephrin-A1-Fc clustered by anti-IgG(Fc) antibody was injected stereotaxically into the ipsilateral lateral ventricle of rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine, and histologic analysis and behavioral tests were performed. Clustered ephrin-A1-Fc transformed the subventricular niche, increasing bromodeoxyuridine-positive cells in the subventricular area, and the cells then migrated to the striatum and differentiated to dopaminergic neurons and astrocytes. In addition, clustered ephrin-A1-Fc enhanced angiogenesis in the striatum on the injected side. Along with histologic improvements, behavioral derangement improved dramatically. These findings indicate that the subventricular niche possesses a mechanism for regulating both stem cell and angiogenic responses via an EphA–mediated signal. We conclude that activation of EphA receptor–mediated signaling by clustered ephrin-A1-Fc from within the lateral ventricle could potentially be utilized in the treatment of neurodegenerative diseases such as Parkinson's disease.