Neuronal migration into injured tissue: mechanisms and therapeutic strategies for brain regeneration

 How will your competent? doctor PRECISELY USE THIS TO MIGRATE NEURONS TO WHERE THEY ARE NEEDED POST STROKE?

And then initiate dendritic branching and axon pathfinding to connect everything up! NO clue! COMPLETE FUCKING INCOMPETENCE, get them fired, it means they have not had one complete thought on stroke recovery ever!

Neuronal migration into injured tissue: mechanisms and therapeutic strategies for brain regeneration

Author links open overlay panel, , 

a

Department of Developmental and Regenerative Neurobiology, Institute of Brain Science (IBS), Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

b

Division of Neural Development and Regeneration, National Institute for Physiological Sciences (NIPS), Okazaki, Japan

Highlights

• •
  New neurons generated in the V-SVZ migrate in the intact and injured brain by regulating cytoskeletal dynamics.
• •
  New neurons migrate to the injured region and replace lost neurons, contributing to the recovery of motor and sensory functions.
• •
  Biomaterials and pharmacological approaches that promote neuronal migration toward injured regions are being actively investigated and may lead to fundamental therapies for brain injury.

Abstract

Neuronal migration is a crucial process not only for brain development but also for neural regeneration after injury. It has been reported that some new neurons generated in the ventricular-subventricular zone (V-SVZ) migrate toward tissue injured by ischemic stroke and other forms of brain damage. These migrating neurons can partially compensate for lost neurons and contribute to functional recovery, including improvements in motor function. Therefore, understanding the mechanisms that regulate neuronal migration is expected to facilitate the development of novel therapeutic strategies that enhance endogenous neural regeneration after brain injury.

In this review, we discuss the migratory mechanisms of new neurons generated in the V-SVZ and summarize current insights into strategies aimed at promoting neuronal migration and neuronal replacement in the injured brain.

Study Reveals How Blood Vessels Drive Neuron Movement in the Brain

 

When neurogenesis creates new brain cells does your competent? doctor have a protocol to guide them where they are needed? Oh, your doctor's two functioning neurons haven't planned for that; WHAT EXACTLY IS YOUR DOCTOR DOING FOR YOUR RECOVERY? Guidelines do not count! Ask and not politely!

Your doctor already knows all about ghrelin, right? Let's see how long incompetency has been occurring!

ghrelin (4 posts to February 2013)

Study Reveals How Blood Vessels Drive Neuron Movement in the Brain

Researchers have discovered how newly created neurons depend on blood flow in the adult brain to travel from their site of origin to their final location.

The study in mice, published today in eLife as the final Version of Record after appearing previously as a Reviewed Preprint, is described by the editors as fundamental. They say it provides convincing evidence that new rostral migratory stream (RMS) neurons are closely situated alongside blood vessels and that their speed of travel through the brain relates to blood flow. The study also suggests that the "hunger hormone" ghrelin, typically known for stimulating appetite, plays a role in the neurons' migration speed.(Will your competent? doctor and hospital ENSURE HUMAN TESTING GETS DONE?)

The findings open avenues to explore unknown factors involved in blood flow-dependent cell migration, which could contribute to the development of novel therapies for neurological diseases.

When neurons are created in the brain, they travel – or migrate – from their site of origin to where they are needed. Several neuron and other cell types migrate along the blood vessels, raising the possibility that blood flow influences migration. In this study, researchers looked at RMS neurons, which originate from the subventricular zone (SVZ) in the brain and migrate through the rostral migratory stream to the olfactory bulb – a region responsible for processing smells. 

"Blood vessels have previously been shown to act as physical 'scaffolds' in the migratory routes of new neurons, but whether blood flow directly affects migration is still unknown," says Takashi Ogino, Assistant Professor in the Department of Developmental and Regenerative Neurobiology, Nagoya City University Graduate School of Medical Sciences, Japan. Ogino is a co-first author of the study alongside Akari Saito, a graduate student in the same department.

Previous studies have revealed that SVZ-derived neurons migrate along blood vessels in the RMS and granule cell layer (GCL), but the interactions between the neurons and vessels along the entire migration route are less clear. So, Ogino, Saito and colleagues began by studying blood vessel-guided neuronal migration in the RMS and olfactory bulb using 3D imaging in adult mice aged 6–12 weeks. This enabled them to analyse the spatial relationship between new neurons and blood vessels.

These experiments confirmed that newborn neurons in the RMS, GCL and other regions frequently use blood vessels as migration scaffolds. Additionally, we saw close spatial relationships between the neurons and blood vessels, indicating that neurons migrate along the vessels for the entire route and that their movement may be influenced by blood flow."

Takashi Ogino, Assistant Professor, Department of Developmental and Regenerative Neurobiology, Nagoya City University Graduate School of Medical Sciences, Japan

To examine this further, the team recorded the flow of new neurons and red blood cells using two-photon laser scanning microscopy. They found that the maximum migration speed was significantly higher for neurons migrating along high-flow vessels than for those in low-flow vessels, suggesting that migration is promoted in regions with abundant blood flow.

In further studies, the team focused on the hormone ghrelin, which can be delivered from the bloodstream to the olfactory bulb and other areas of the brain through vascular walls. They applied fluorescently labelled ghrelin to the bloodstream in mice and saw that it accumulated in vascular endothelial cells – the cells that form the lining of blood-vessels – and parenchymal tissue in the RMS and olfactory bulb. This indicates that blood-derived ghrelin crosses the vascular wall into the functional tissue of the brain (brain parenchyma) and is delivered to new neurons. They also noticed that ghrelin signalling promoted somal translocation – the process by which the cell body (soma) reaches out to bring the neuron to its final location – by activating the contraction of the actin cytoskeleton at the rear of the cell soma.

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The team then examined whether calorie restriction, which has been reported to increase ghrelin levels in the blood, affects neuronal migration. They restricted the calorie intake of mice and found that this promoted the migration of olfactory bulb neurons.

"Together, these experiments suggest that blood flow promotes the migration of olfactory bulb neurons during hunger through ghrelin signalling, and this in turn increases the number of mature neurons in the olfactory bulb," says co-first author Akari Saito. "This could be a key mechanism that improves the olfactory function for sniffing out food when hungry."

The authors add that neuronal migration may be influenced by blood flow under pathological conditions, as well as the conditions used in their study.

"It is possible that blood contains factors other than ghrelin that are beneficial to neuronal migration," says senior author Kazunobu Sawamoto, Professor at the Department of Developmental and Regenerative Neurobiology, Nagoya City University Graduate School of Medical Sciences. "More studies are therefore needed to identify these and other factors in the mechanism of blood flow-dependent cell migration. This could lead to the development of new blood flow-based therapies for neurological conditions such as stroke and vascular dementia."

Source:

eLife

Journal reference:

Ogino, T., et al. (2025). Neuronal migration depends on blood flow in the adult mammalian brain. eLife. doi.org/10.7554/elife.99502.3

Hunger Hormone and Blood Flow Team Up to Guide New Brain Cells

 When neurogenesis creates new brain cells does your competent? doctor have a protocol to guide them where they are needed? Oh, your doctor's two functioning neurons haven't planned for that; WHAT EXACTLY IS YOUR DOCTOR DOING FOR YOUR RECOVERY? Guidelines do not count! Ask and not politely!

Your doctor already knows all about ghrelin, right? Let's see how long incompetency has been occurring!

ghrelin (4 posts to February 2013)

Hunger Hormone and Blood Flow Team Up to Guide New Brain Cells

Summary: Scientists have discovered that blood flow helps direct the movement of newly formed neurons in the adult brain, revealing a surprising link between circulation and brain cell migration. Using advanced imaging, researchers found that neurons travel faster along high-flow blood vessels, and that the hunger hormone ghrelin boosts this migration by activating movement within the cells.

Calorie restriction, which raises ghrelin levels, further accelerated neuron movement to the olfactory bulb—the brain’s smell center. The findings reveal how hunger-related signals and blood dynamics shape brain regeneration, offering clues for new treatments for stroke and neurodegenerative diseases.

Key Facts

• Flow-Driven Movement: Neurons migrate faster along blood vessels with higher blood flow.
• Hormonal Influence: Ghrelin, the hunger hormone, enhances neuron migration by triggering internal cell motion.
• Therapeutic Potential: Blood flow–based mechanisms could inspire new therapies for stroke and vascular dementia.

Source: eLife

Researchers have discovered how newly created neurons depend on blood flow in the adult brain to travel from their site of origin to their final location.

The study in mice, published today in eLife as the final Version of Record after appearing previously as a Reviewed Preprint, is described by the editors as fundamental.(Will your competent? doctor and hospital ENSURE HUMAN TESTING GETS DONE?)

The authors add that neuronal migration may be influenced by blood flow under pathological conditions, as well as the conditions used in their study. Credit: Neuroscience News

They say it provides convincing evidence that new rostral migratory stream (RMS) neurons are closely situated alongside blood vessels and that their speed of travel through the brain relates to blood flow.

The study also suggests that the “hunger hormone” ghrelin, typically known for stimulating appetite, plays a role in the neurons’ migration speed.

The findings open avenues to explore unknown factors involved in blood flow-dependent cell migration, which could contribute to the development of novel therapies for neurological diseases.

When neurons are created in the brain, they travel – or migrate – from their site of origin to where they are needed. Several neuron and other cell types migrate along the blood vessels, raising the possibility that blood flow influences migration.

In this study, researchers looked at RMS neurons, which originate from the subventricular zone (SVZ) in the brain and migrate through the rostral migratory stream to the olfactory bulb – a region responsible for processing smells. 

“Blood vessels have previously been shown to act as physical ‘scaffolds’ in the migratory routes of new neurons, but whether blood flow directly affects migration is still unknown,” says Takashi Ogino, Assistant Professor in the Department of Developmental and Regenerative Neurobiology, Nagoya City University Graduate School of Medical Sciences, Japan. Ogino is a co-first author of the study alongside Akari Saito, a graduate student in the same department.

Previous studies have revealed that SVZ-derived neurons migrate along blood vessels in the RMS and granule cell layer (GCL), but the interactions between the neurons and vessels along the entire migration route are less clear.

“Additionally, we saw close spatial relationships between the neurons and blood vessels, indicating that neurons migrate along the vessels for the entire route and that their movement may be influenced by blood flow.”

To examine this further, the team recorded the flow of new neurons and red blood cells using two-photon laser scanning microscopy. They found that the maximum migration speed was significantly higher for neurons migrating along high-flow vessels than for those in low-flow vessels, suggesting that migration is promoted in regions with abundant blood flow.

In further studies, the team focused on the hormone ghrelin, which can be delivered from the bloodstream to the olfactory bulb and other areas of the brain through vascular walls.

They applied fluorescently labelled ghrelin to the bloodstream in mice and saw that it accumulated in vascular endothelial cells – the cells that form the lining of blood-vessels – and parenchymal tissue in the RMS and olfactory bulb. This indicates that blood-derived ghrelin crosses the vascular wall into the functional tissue of the brain (brain parenchyma) and is delivered to new neurons.

They also noticed that ghrelin signalling promoted somal translocation – the process by which the cell body (soma) reaches out to bring the neuron to its final location – by activating the contraction of the actin cytoskeleton at the rear of the cell soma.

The team then examined whether calorie restriction, which has been reported to increase ghrelin levels in the blood, affects neuronal migration. They restricted the calorie intake of mice and found that this promoted the migration of olfactory bulb neurons.

“Together, these experiments suggest that blood flow promotes the migration of olfactory bulb neurons during hunger through ghrelin signalling, and this in turn increases the number of mature neurons in the olfactory bulb,” says co-first author Akari Saito.

“This could be a key mechanism that improves the olfactory function for sniffing out food when hungry.”

The authors add that neuronal migration may be influenced by blood flow under pathological conditions, as well as the conditions used in their study.

“It is possible that blood contains factors other than ghrelin that are beneficial to neuronal migration,” says senior author Kazunobu Sawamoto, Professor at the Department of Developmental and Regenerative Neurobiology, Nagoya City University Graduate School of Medical Sciences.

So, Ogino, Saito and colleagues began by studying blood vessel-guided neuronal migration in the RMS and olfactory bulb using 3D imaging in adult mice aged 6–12 weeks. This enabled them to analyse the spatial relationship between new neurons and blood vessels.

“These experiments confirmed that newborn neurons in the RMS, GCL and other regions frequently use blood vessels as migration scaffolds,” Ogino explains.

“More studies are therefore needed to identify these and other factors in the mechanism of blood flow-dependent cell migration. This could lead to the development of new blood flow-based therapies for neurological conditions such as stroke and vascular dementia.”

Key Questions Answered:

Q: How does blood flow affect the migration of new neurons?

A: Neurons move faster along vessels with stronger blood flow, suggesting circulation directly supports their movement through the brain.

Q: What role does the hormone ghrelin play in this process?

A: Ghrelin crosses from the bloodstream into brain tissue, where it activates neuron movement and helps guide cells to their destination.

Q: Why does this discovery matter?

A: It shows that hunger and blood flow work together to shape brain regeneration—potentially paving the way for treatments that enhance recovery after brain injury.

About this neuroscience research news

Author: Emily Packer
Source: eLife
Contact: Emily Packer – eLife
Image: The image is credited to Neuroscience News

A mathematical model suggests collectivity and inconstancy enhance the efficiency of neuronal migration in the adult brain

 Does your competent? doctor have the EXACT PROTOCOLS that will migrate neurons to where they are needed? 

Your competent? doctor has been working on this for 6 months already, right? Oh no, you DON'T have a functioning stroke doctor, do you?

Push-and-Pull Signals Direct Neuron Migration in the Developing Brain January 2025 

The latest here:

A mathematical model suggests collectivity and inconstancy enhance the efficiency of neuronal migration in the adult brain

•  Daiki Wakita,
• Yuriko Sobu,
• Naoko Kaneko ,
• Takeshi Kano

• Daiki Wakita, 
• Yuriko Sobu, 
• Naoko Kaneko, 
• Takeshi Kano

x

• Published: June 5, 2025
• https://doi.org/10.1371/journal.pcbi.1013105

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Abstract

Neuronal regeneration in the adult brain, which is restricted compared to that in the embryonic brain, is a long-standing topic in neuroscience and medical research. Based on studies in mammals, a small number of newly generated immature neurons (neuroblasts) migrate toward damaged sites and contribute to functional recovery. During migration, neuroblasts form chain-like collectives and modify the morphology of glial cells (astrocytes), which are the main components of the surrounding environment. However, it remains unclear how neuroblasts form collectives and how efficient migration is achieved through collective formation in a pool of astrocytes. The main difficulty lies in tracking individual neuroblasts within the collective, both in vitro and in vivo, over a period. To address this impasse, we built a mathematical model of the neuroblast-astrocyte system to assess its long-term performance in silico. Our simulations showed that individual neuroblasts gathered into chain-like collectives through occasional contact, astrocyte confinement, and moderate adhesion between the neuroblasts. The forward movement of neuroblasts in an astrocyte-dense environment was accelerated if we assumed a simple interaction: the higher the number of neuroblasts near an astrocyte, the stronger the shrinkage of astrocytic protrusions. Furthermore, temporal changes in neuroblast behavior, as indicated by our observation of living neuroblasts in culture, reinforce the advantages of simulated collectives. A collective of neuroblasts with constant behavior sometimes repeated non-migratory movements, whereas those with inconstant behavior were easily untangled, resulting in a rapid migration. These results highlight the potential for neuroblast collectivity and inconstancy in enhancing neuronal regeneration in the adult brain.

Author summary

Increasing the regenerative ability of the adult brain is challenging for humans. Only a limited number of newly generated nerve cells (neurons) migrate toward injured regions to participate in the functional regeneration of the adult mammalian brain. During this journey, neurons gather and modify the shape of the surrounding glial cells. Because it is difficult to observe how actual neurons within a group efficiently move in the brain for a long time, we sought to determine the key to rapid migration using a mathematical approach instead of a biological one. Computer simulations showed that, first, neurons form a chain-like group by gently sticking to each other and following the rail-like guide of glial cells. Second, a group of neurons migrates faster than a single one because they can shrink the processes of nearby glial cells more effectively than a single one. Third, a group becomes faster when the behavior of neurons varies over time, even at the same average speed. Our novel concept posits that high regeneration ability in the brain is achieved through the grouped, temporally varying migration of neurons.

Figures

Push-and-Pull Signals Direct Neuron Migration in the Developing Brain

 How will your competent? doctors get this mimicked post stroke to encourage dendritic branching and axon pathfinding to get your neurons to reroute around damaged areas?

Look at that, over a decade for your competent? doctor to get solutions for this! Did they? 

• axon pathfinding (35 posts to March 2012)

• dendritic branching (38 posts to February 2012)

• neurite outgrowth (29 posts to January 2012)

• netrin-1 (4 posts to January 2012)

Push-and-Pull Signals Direct Neuron Migration in the Developing Brain

Summary: Scientists have uncovered how developing neurons migrate from the germinal zone, a process critical for proper brain circuit formation. They identified a “push-pull” system where the guidance molecule Netrin-1 repels differentiated neurons, while the ubiquitin ligase Siah2 prevents premature migration by degrading essential proteins.

The interplay of these signals creates a coincidence detection circuit that precisely regulates neuron movement and direction. Super-resolution microscopy revealed how proteins like Pard3 and JamC enable the coordination of adhesion and guidance signals.

Key Facts

• Push-Pull Mechanism: Netrin-1 repels differentiated neurons, while Siah2 prevents premature migration by degrading migration-related proteins.
• Coincidence Detection Circuit: Proteins Pard3 and JamC coordinate adhesion and guidance signals to ensure precise neuronal migration.
• Significance for Brain Development: Findings offer insights into how molecular signals drive neuron positioning for proper cerebellum function.

Source: St. Jude Children’s Research Hospital

The journey of a thousand miles begins with a single step, but for developing neurons, this first step relies on collaboration from multiple signaling pathways.

Scientists at St. Jude Children’s Research Hospital used fluorescent imaging techniques to track the sequence of molecular events that kickstart the migration of developing neurons, implicating an intricate circuit of cues in the process.

This previously unappreciated “coincidence detection circuit” highlights that the interplay of these opposing pathways ensures proper neuronal migration. Credit: Neuroscience News

The findings, which shed light on the processes that ensure proper cerebellum development, were published today in Nature Communications.

Neurons develop in a region of the brain called the germinal zone, but to fulfill their functions, they must travel to other parts of the brain where they are needed to form circuits.

The series of cues telling them to leave have not been fully understood, but David Solecki, PhD, St. Jude Department of Developmental Neurobiology, was well positioned to unravel how these cues come together to kickstart neuron migration. 

“In the past, people have looked at important cytoskeletal components and extrinsic signals from outside the cell, which tell neurons when and where to go,” Solecki said.

“But the key challenge becomes figuring out how they are integrated. How do multiple biological pathways come together to orchestrate this germinal zone exit event?”

The results revealed that antagonism between the guidance molecule Netrin-1 “pushing” developed neurons out of the germinal zone and the ubiquitin ligase Siah2 “pulling” undeveloped cells back into the germinal zone is responsible.

This previously unappreciated “coincidence detection circuit” highlights that the interplay of these opposing pathways ensures proper neuronal migration.

Push-and-pull regulates neuron migration 

Solecki used super-resolution microscopy to reveal how this two-switch circuit worked. The researchers first noted that differentiated neurons appeared to migrate away from Netrin-1 in the germinal zone. This protein is detected and repulsed by the transmembrane receptor, Dcc.

“Netrin-1 is secreted by the progenitor cells, and it tells the newly differentiated cells, ‘You have to go away from us,’” Solecki explained.

“The differentiated cells are essentially repulsed by their previous cohort of immature neurons.”

A deeper look at the basis of coincidence detection revealed a circuit between Netrin-1–Dcc signaling and two other proteins, Pard3 and JamC. These give Dcc clustering and adhesion cues at sites essential for migration.

Pard3 promotes the movement and localization of Dcc receptors, while JamC anchors them at adhesion sites, enabling effective polarity and adhesion cue integration. This complex balances adhesion and guidance signaling to regulate neuronal migration timing and direction. 

This “push” signal is balanced by a “pull” signal, driven by the ubiquitin ligase, Siah2. Ubiquitin ligases facilitate the recycling of defunct proteins. Siah2 is the assigned ubiquitin ligase for Dcc and Pard3. 

The researchers demonstrated that Siah2 prevents premature migration of undeveloped neurons from the germinal zone by degrading Dcc, the Netrin-1 sensor, and Pard3, which regulates Dcc and JamC movement.

This degradation precisely controls the interaction of adhesion and guidance cues within the coincidence detection circuit.

The findings provided unique insight into how this collective system forms a coincidence detection circuit, wherein cell–cell contact and Netrin-1 sensing inputs must function for the correct output to be seen.

“With other techniques such as single-cell sequencing, you look at the genes behind the systems, but eventually, the cell biology is something you must figure out,” Solecki said.

“And that’s what this work was about: the intricate interplay of the molecules.”

Authors and funding

The study’s first author is Christophe Laumonnerie, St. Jude. The study’s other authors are Tommy Lewis Jr., Oklahoma Medical Research Foundation; and Maleelo Shamambo, Daniel Stabley, Niraj Trivedi, and Danielle Howell, St. Jude

The study was supported by grants from the National Institute of Neurological Disorders (NINDS), and the American Lebanese Syrian Associated Charities (ALSAC), the fundraising and awareness organization of St. Jude.

About this neurodevelopment research news

Author: Chelsea Bryant
Source: St. Jude Children’s Research Hosptial
Contact: Chelsea Bryant – St. Jude Children’s Research Hospital
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit” by David Solecki, et al. Nature Communications

Na+ channel β subunits: overachievers of the ion channel family

They talk about helping migration, a useful thing to understand about neurogenesis. 

Na+ channel β subunits: overachievers of the ion channel family

Voltage-gated Na⁺ channels (VGSCs) in mammals contain a pore-forming α subunit and one or more β subunits. There are five mammalian β subunits in total: β1, β1B, β2, β3, and β4, encoded by four genes: SCN1B–SCN4B. With the exception of the SCN1B splice variant, β1B, the β subunits are type I topology transmembrane proteins. In contrast, β1B lacks a transmembrane domain and is a secreted protein. A growing body of work shows that VGSC β subunits are multifunctional. While they do not form the ion channel pore, β subunits alter gating, voltage-dependence, and kinetics of VGSCα subunits and thus regulate cellular excitability in vivo. In addition to their roles in channel modulation, β subunits are members of the immunoglobulin superfamily of cell adhesion molecules and regulate cell adhesion and migration. β subunits are also substrates for sequential proteolytic cleavage by secretases. An example of the multifunctional nature of β subunits is β1, encoded by SCN1B, that plays a critical role in neuronal migration and pathfinding during brain development, and whose function is dependent on Na⁺ current and γ-secretase activity. Functional deletion of SCN1B results in Dravet Syndrome, a severe and intractable pediatric epileptic encephalopathy. β subunits are emerging as key players in a wide variety of physiopathologies, including epilepsy, cardiac arrhythmia, multiple sclerosis, Huntington’s disease, neuropsychiatric disorders, neuropathic and inflammatory pain, and cancer. β subunits mediate multiple signaling pathways on different timescales, regulating electrical excitability, adhesion, migration, pathfinding, and transcription. Importantly, some β subunit functions may operate independently of α subunits. Thus, β subunits perform critical roles during development and disease. As such, they may prove useful in disease diagnosis and therapy.

Introduction

Mammalian voltage-gated Na⁺ channels (VGSCs) exist as macromolecular complexes in vivo, comprising, at minimum, one pore-forming α subunit and one or more β subunits in a 1:1 stoichiometry for α:β (Catterall, 1992). Traditionally, VGSC β subunits have been termed “auxiliary.” However, increasing evidence suggests that the β subunits are far from auxiliary, and, in fact, function as critical signaling molecules in their own right, perhaps even independently of α subunits. In this review, we will summarize the latest developments describing the growing, diverse, multifunctional roles of the β subunits, including their contribution to human disease