ICAM-5: A Neuronal Dendritic Adhesion Molecule Involved in Immune and Neuronal Functions

What is your doctor doing to make sure your dendrites are traveling to the appropriate damaged area?
http://link.springer.com/chapter/10.1007/978-1-4614-8090-7_6

• Carl G. Gahmberg M.D.,
• Lin Ning M.Sc.,
• Sonja Paetau B.Sc.

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Abstract

The neuron-specific intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a member of the ICAM family of adhesion proteins. It has a complex structure with nine external immunoglobulin domains followed by a transmembrane and a cytoplasmic domain. The external part binds to β1- and β2-integrins and the matrix protein vitronectin, whereas its transmembrane domain binds to presenilins and the cytoplasmic domain to α-actinin and the ERM family of cytoplasmic proteins. In neurons it is confined to the soma and dendrites and it is enriched in dendritic filopodia with less expression in more mature dendritic spines. ICAM-5 strongly stimulates neurite outgrowth. ICAM-5 is cleaved by matrix metalloproteases upon activation of glutamate receptors or degraded through endocytosis resulting in increased spine maturation. Ablation of ICAM-5 expression increases functional synapse formation. The cleaved soluble fragment of ICAM-5 is immunosuppressive, which may be important in neuronal inflammatory diseases.

Bidirectional influence of sodium channel activation on NMDA receptor–dependent cerebrocortical neuron structural plasticity

Ask your doctor what the hell this means, it sounds very important to us. And if we had decent stroke associations we could go to them for answers. But no, its every survivor and doctor for themselves.
http://www.pnas.org/content/early/2012/11/09/1212584109.short

Abstract

Neuronal activity regulates brain development and synaptic plasticity through N-methyl-d-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na⁺]_i) also exerts a regulatory influence on NMDAR channel activity, and [Na⁺]_i may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na⁺]_i in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na⁺] and [Ca²⁺]. Pharmacological evaluation showed that PbTx-2–induced Ca²⁺ influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca²⁺ influx. PbTx-2–exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization, and synaptogenesis all exhibited bidirectional concentration–response profiles. This profile paralleled that of NMDA, which also produced bidirectional concentration–response profiles for neurite outgrowth and synaptogenesis. These data are consistent with the hypothesis that PbTx-2–enhanced neuronal plasticity involves NMDAR-dependent signaling. Our results demonstrate that PbTx-2 mimics activity-dependent neuronal structural plasticity in cerebrocortical neurons through an increase in [Na⁺]_i, up-regulation of NMDAR function, and engagement of downstream Ca²⁺-dependent signaling pathways. These data suggest that VGSC gating modifiers may represent a pharmacologic strategy to regulate neuronal plasticity through NMDAR-dependent mechanisms.

First micro-structure atlas of the human brain completed

And with this our doctors need to come up with a stroke protocol to recover the damage to our white matter networks.  I'm assuming  I lost a good chunk of my white matter underlying my motor and pre-motor cortex.  Do we need myelin repair?, axonal sprouting? filopodia searching? dendritic branching?
http://www.alphagalileo.org/ViewItem.aspx?ItemId=125106&CultureCode=en
A European team of scientists have built the first atlas of white-matter microstructure in the human brain. The project’s final results have the potential to change the face of neuroscience and medicine over the coming decade.
The work relied on groundbreaking MRI technology and was funded by the EU’s future and emerging technologies program with a grant of 2.4 million Euros. The participants of the project, called CONNECT, were drawn from leading research centers in countries across Europe including Israel, United Kingdom, Germany, France, Denmark, Switzerland and Italy.
The project investigators met today in Paris, after 3 years of research, to announce the conclusion of the project and present a report of their findings.
The new atlas combines three-dimensional images from the MRI scans of 100 brains of volunteers. To achieve this, CONNECT developed advanced MRI methods providing unprecedented detail and accuracy.
Professor Daniel Alexander, a CONNECT steering committee member from the UCL Department of Computer Science said: "The UCL team use the latest computer modelling algorithms and hardware to invent new imaging techniques. The techniques we devised were key to realising the new CONNECT brain atlas."
"The imaging techniques reveal new information about brain structure that help us understand how low-level cellular architecture relate to high-level thought processes."
Currently, biomedical research teams around the world studying brain science rely on a brain atlas produced by painstaking and destructive histological methods on the brains of a few individuals who donated their bodies to science.
The new atlas simulates the impossible process of painstakingly examining every mm2 of brain tissue (of which there are around 100 million per brain) with a microscope, while leaving the brain in tact.
The key novelty in the atlas is the mapping of microscopic features (such as average cell size and packing density) within the white matter, which contains the neuronal fibers that transmit information around the living brain. The results of the project, obtained through advanced image processing techniques, provide new depth and accuracy in our understanding of the human brain in health and disease.
The atlas describes the brain's microstructure in standardized space, which enables non-expert users, such as physicians or medical researchers, to exploit the wealth of knowledge it contains. The atlas contains a variety of new images that represent different microscopic tissue characteristics, such as the fiber diameter and fiber density across the brain, all estimated using MRI. These images will serve as the reference standard of future brain studies in both medicine and basic neuroscience.
The project will dramatically facilitate and promote future research into white matter structure and function. Historically in neuroscience, the vast majority of research effort has been invested in understanding and studying gray matter and neurons, while white matter has received relatively little attention.
This owes largely to the lack of effective research tools to study white matter, even though it comprises about half the volume of the brain. The new MRI methods that were developed in CONNECT allow researchers, for the first time, to visualize the micro-structure of the living brain over the whole brain.
This opens new realms in our understanding of our most complex organ. In the future, the project members intend to use the technology they have developed to study the dynamics and time dependence of the micro-structure in white matter. For example they will search for a finger print or a trace that a cognitive task imprints on white matter microstructure encoding new experiences in the wiring of the brain.
Another future direction is to characterize and understand micro-structural changes caused by different neurodegenerative diseases, such as Alzheimer's or schizophrenia, in order to develop better diagnostic procedures for these and other devastating conditions.

The 69 page report here:
http://www.alphagalileo.org/AssetViewer.aspx?AssetId=68892&CultureCode=en

ProBDNF Collapses Neurite Outgrowth of Primary Neurons by Activating RhoA

I am assuming that  not only do you need BDNF, you need to make sure the precursor BDNF does not hang around. Lets get some human testing.

ProBDNF Collapses Neurite Outgrowth of Primary Neurons by Activating RhoA

Background

Neurons extend their dendrites and axons to build functional neural circuits, which are regulated by both positive and negative signals during development. Brain-derived neurotrophic factor (BDNF) is a positive regulator for neurite outgrowth and neuronal survival but the functions of its precursor (proBDNF) are less characterized.

Methodology/Principal Findings

Here we show that proBDNF collapses neurite outgrowth in murine dorsal root ganglion (DRG) neurons and cortical neurons by activating RhoA via the p75 neurotrophin receptor (p75NTR). We demonstrated that the receptor proteins for proBDNF, p75NTR and sortilin, were highly expressed in cultured DRG or cortical neurons. ProBDNF caused a dramatic neurite collapse in a dose-dependent manner and this effect was about 500 fold more potent than myelin-associated glycoprotein. Neutralization of endogenous proBDNF by using antibodies enhanced neurite outgrowth in vitro and in vivo, but this effect was lost in p75NTR^−/− mice. The neurite outgrowth of cortical neurons from p75NTR deficient (p75NTR^−/−) mice was insensitive to proBDNF. There was a time-dependent reduction of length and number of filopodia in response to proBDNF which was accompanied with a polarized RhoA activation in growth cones. Moreover, proBDNF treatment of cortical neurons resulted in a time-dependent activation of RhoA but not Cdc42 and the effect was absent in p75NTR^−/− neurons. Rho kinase (ROCK) and the collapsin response mediator protein-2 (CRMP-2) were also involved in the proBDNF action.

Conclusions

proBDNF has an opposing role in neurite outgrowth to that of mature BDNF. Our observations suggest that proBDNF collapses neurites outgrowth and filopodial growth cones by activating RhoA through the p75NTR signaling pathway.

Signaling Required for Blood Vessel Maintenance: Molecular Basis and Pathological Manifestations

This one is heavy going but they do talk about pericytes, which is a cause of neuronal death, and filopodia signaling. They should have been able to summarize it in a couple of sentences or at least farmed it out to a neurologist well-versed in stroke to get his/her take on it.
This is not directly related to stroke but to me it is invaluable to understand it.

http://www.hindawi.com/journals/ijvm/2012/293641/
abstract only, read the whole thing at the url.
AbstractAs our understanding of molecular mechanisms leading to vascular formation increases, vessel maintenance including stabilization of new vessels and prevention of vessel regression began to be considered as an active process that requires specific cellular signaling. While signaling pathways such as VEGF, FGF, and angiopoietin-Tie2 are important for endothelial cell survival and junction stabilization, PDGF and TGF-β signaling modify mural cell (vascular smooth muscle cells and pericytes) functions, thus they fortify vessel integrity. Breakdown of these signaling systems results in pathological hyperpermeability and/or genetic vascular abnormalities such as vascular malformations, ultimately progressing to hemorrhage and edema. Hence, blood vessel maintenance is fundamental to controlling vascular homeostasis and tissue functions. This paper discusses signaling pathways essential for vascular maintenance and clinical conditions caused by deterioration of vessel integrity.

Central Nervous System Tissue Engineering: Current Considerations and Strategies

The abstract just hints at the possibilities of neuron reconnections. To be a researcher having access to complete articles would be wonderful.
http://www.morganclaypool.com/doi/abs/10.2200/S00390ED1V01Y201111TIS008

Abstract

Combating neural degeneration from injury or disease is extremely difficult in the brain and spinal cord, i.e. central nervous system (CNS). Unlike the peripheral nerves, CNS neurons are bombarded by physical and chemical restrictions that prevent proper healing and restoration of function. The CNS is vital to bodily function, and loss of any part of it can severely and permanently alter a person's quality of life. Tissue engineering could offer much needed solutions to regenerate or replace damaged CNS tissue. This review will discuss current CNS tissue engineering approaches integrating scaffolds, cells and stimulation techniques. Hydrogels are commonly used CNS tissue engineering scaffolds to stimulate and enhance regeneration, but fiber meshes and other porous structures show specific utility depending on application. CNS relevant cell sources have focused on implantation of exogenous cells or stimulation of endogenous populations. Somatic cells of the CNS are rarely utilized for tissue engineering; however, glial cells of the peripheral nervous system (PNS) may be used to myelinate and protect spinal cord damage. Pluripotent and multipotent stem cells offer alternative cell sources due to continuing advancements in identification and differentiation of these cells. Finally, physical, chemical, and electrical guidance cues are extremely important to neural cells, serving important roles in development and adulthood. These guidance cues are being integrated into tissue engineering approaches. Of particular interest is the inclusion of cues to guide stem cells to differentiate into CNS cell types, as well to guide neuron targeting. This review should provide the reader with a broad understanding of CNS tissue engineering challenges and tactics, with the goal of fostering the future development of biologically inspired designs.

Table of Contents: Introduction / Anatomy of the CNS and Progression of Neurological Damage / Biomaterials for Scaffold Preparation / Cell Sources for CNS TE / Stimulation and Guidance / Concluding Remarks

This should prompt more questions and a host of new research studies.

Growth cone steering by a physiological electric field requires dynamic microtubules, microfilaments and Rac-mediated filopodial asymmetry

Maybe they could direct movement of the growth cones by magnetic nanoparticles.
http://jcs.biologists.org/content/119/9/1736.abstract

1. Ann M. Rajnicek*,
2. Louise E. Foubister and
3. Colin D. McCaig

+ Author Affiliations

1. School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, AB25 2ZD, UK

1. * Author for correspondence (e-mail: a.m.rajnicek@abdn.ac.uk)

Summary

Electric fields (EFs) resembling those in the developing and regenerating nervous systems steer growth cones towards the cathode. Requirements for actin microfilaments, microtubules and their interactions during EF growth cone steering have been presumed, but remain unproven. Here, we demonstrate essential roles for dynamic microfilaments and microtubules in cathode-directed migration. Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was attenuated significantly by nanomolar concentrations of the microfilament inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule-destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of filopodia preceded cathodal turning of the growth cone, suggesting an instructive role in EF-induced steering. Lamellipodial asymmetry accompanied turning. Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac, respectively, and, as shown in the companion paper in this issue, peptides that selectively prevented effector binding to the CRIB domains of Cdc42 or Rac abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the Rac peptide suppressed lamellipodium formation, increased the number of filopodia, abolished cathodal filopodial orientation, and prevented cathodal steering. The Cdc42 peptide suppressed filopodium formation, increased lamellipodial area and prevented cathodal steering. The cathodal bias of lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for cathodal steering in the absence of filopodia, but the cathodal bias of filopodia through Rac CRIB activity was necessary for cathodal turning. Understanding the mechanism for cathodal growth cone guidance will enhance the emerging clinical effort to stimulate human spinal cord regeneration through EF application.

Filopodia: The Fingers That Do the Walking

An even better explanation of filopodia.
http://stke.sciencemag.org/cgi/content/abstract/2007/400/re5

Stephanie L. Gupton^* and Frank B. Gertler

Department of Biology, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Abstract: Filopodia are actin-based structures composed of parallel bundles of actin filaments and various actin-associated proteins, and they play important roles in cell-cell signaling, guidance toward chemoattractants, and adhesion to the extracellular matrix. Two mechanisms for the formation of filopodia have been suggested, each using different sets of actin-regulating proteins, creating some controversy in the field. New molecules, some of unknown functions, have also been implicated in filopodium formation, suggesting that other possible mechanisms of filopodium formation exist. We discuss established and novel proteins that mediate the formation and dynamics of filopodia, different mechanisms of filopodium formation, and the various functions that distinct filopodia perform.

*Corresponding author. E-mail: gupton@mit.edu

Growth Cone Pathfinding and Filopodial Dynamics Are Mediated Separately by Cdc42 Activation

More on growth cones. My fascination with this topic is due to my probable need to have neurogenesis work for me in order to completely recover. I won't settle for anything less.
http://neuro.cjb.net/content/22/5/1794.short

1. Michael D. Kim1,
2. Peter Kolodziej2, and
3. Akira Chiba1

+ Author Affiliations

1. ¹Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois 61801, and
2. ²Department of Cell and Developmental Biology, Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, Tennessee 37232

Abstract

Although evidence exists that activation of the Rho family GTPase Cdc42 affects axonal development, its specific roles within a growth cone are not well delineated. To evaluate the model that Cdc42 activation regulates growth cone navigation by promoting filopodial activity, we adopted a live analysis strategy that uses transgenicDrosophila lines in which neurons coexpressed constitutively active Cdc42 (Cdc42^V12) and membrane-targeted green fluorescent protein. We found that growth cones that displayed pathfinding defects exhibited little change in their filopodial activity, whereas others without pathfinding defects exhibited an ∼50% increase in their filopodial activity. Moreover, effector loop mutations that were added to the constitutively active Cdc42 (Cdc42^V12C40 and Cdc42^V12A37) exerted little influence over filopodial activity caused by Cdc42 activation but suppressed the pathfinding defects of the growth cones. Together, these data suggest that Cdc42 controls filopodial activity in axonal growth cones independently of its effects on their pathfinding.