Ischemic stroke triggers brain-wide synaptic remodeling within four hours

 How will your competent? doctor use this TO GET YOU RECOVERED? Sorry, DOING NOTHING, LIKE USUAL!

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Ischemic stroke triggers brain-wide synaptic remodeling within four hours

 Huanhuan Chen  

Ye Wei, 

Luminiţa Ruje, 

Fusheng Du, 

Zhendong Feng, 

Oleg O. Glebov  

Published: March 2, 2026 

https://doi.org/10.1371/journal.pbio.3003608 

Abstract

Physiological mechanisms of the key hyperacute (0–24 hours) stage of stroke are poorly understood, hampering the development of new therapies. Synaptic plasticity has been strongly implicated in early stages of neurodegenerative and neurodevelopmental disorders, yet its relevance in early stroke remains unclear. Here, we describe the emergence of distinct region-specific forms of synaptic remodeling following middle cerebral artery occlusion in rats, arising within the critical 4-hour period. Synapses within the severely ischemic core region were rapidly lost, while those in the mildly ischemic penumbra, albeit largely structurally intact, were functionally diminished. In contrast, the contralateral cortex exhibited increased synaptic staining and synaptic vesicle cycling. Systemic pharmacological blockade of NMDA-type glutamate receptors abolished contralateral synaptic increase and exacerbated synaptic decline in the penumbra. Proteomic and transcriptomic analyses showed that cross-brain synaptic plasticity is independent of local gene expression and revealed metabolic rearrangement and synaptic downregulation in the penumbra. These findings identify brain-wide synaptic rebalancing as a potential mechanism for rapid functional compensation in hyperacute stroke, highlighting the extent of brain response to acute perturbation.

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Citation: Chen H, Wei Y, Ruje L, Du F, Feng Z, Wan Q, et al. (2026) Ischemic stroke triggers brain-wide synaptic remodeling within four hours. PLoS Biol 24(3): e3003608. https://doi.org/10.1371/journal.pbio.3003608

Academic Editor: Richard Daneman, UCSD, UNITED STATES OF AMERICA

Received: August 26, 2025; Accepted: January 6, 2026; Published: March 2, 2026

Copyright: © 2026 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are contained within the paper and its Supporting information files, or freely available online. Proteomics data were analyzed by Oe Biotech using a proprietary pipeline. Mass spectrometry proteomics data is available at ProteomeXchange (https://proteomecentral.proteomexchange.org, dataset identifier PXD058834). Custom code for gene expression analysis has been uploaded to Zenodo (https://zenodo.org/records/17987265). RNAseq data is available at GEO (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE283465). Numerical data is presented in S1 Table.

Neuroplasticity-related effects of vitamin D relevant to its neuroprotective effects: A narrative review

 Ask your competent? doctor for EXACT PROTOCOLS on how to get synaptogenesis, dendritic branching and axon pathfinding done so you can recover from your stroke. Your doctor better know all about these and how to get the connections done!

Synaptogenesis is the formation of synapses between neurons in the nervous system. 

Neuroplasticity-related effects of vitamin D relevant to its neuroprotective effects: A narrative review

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https://doi.org/10.1016/j.pbb.2024.173899

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Highlights

• •
  The neuroplasticity-related mechanisms of vitamin D are discussed.
• •
  The increased expression of neurotrophins and their receptors by vitamin D is reviewed.
• •
  The modulation of synaptogenesis by vitamin D is provided.
• •
  The role of vitamin D in depression, Parkinson's and Alzheimer's disease is examined.

Abstract

The pathophysiology of a wide range of central nervous system (CNS) disorders, such as neurodegenerative and psychiatric diseases, has been associated with impairment of neurogenic and synaptogenic processes. Therefore, pharmacological and/or nutritional strategies based on the stimulation and/or restoration of these processes may have beneficial effects against diseases in which these processes are impaired. In this context, vitamin D has emerged as a promising neuroprotective compound. Due to its pleiotropic properties, it can interact with multiple molecular targets and thereby affect different cell types, including neurons and glial cells. This neurosteroid contributes to CNS homeostasis by non-genomic and genomic mechanisms through its interaction with vitamin D receptors (VDRs). Among several properties of this vitamin, its role in neuronal proliferation and differentiation as well as in synaptic plasticity has received attention. Considering this background, this narrative review aims to highlight the neuroplasticity-related mechanisms of vitamin D that may be associated with its neuroprotective effects.(What are the amounts?)

Introduction

The mechanisms regulated by vitamin D are not limited to its involvement in the regulation of bone metabolism and calcium homeostasis. Its role in cell differentiation and immune system function has been extensively studied. In addition, the role of vitamin D in brain development and function has attracted particular interest in recent decades (Kesby et al., 2011; Cui and Eyles, 2022). Evidence suggests that vitamin D is a pleiotropic molecule capable of interacting directly with multiple targets (Kouba et al., 2024), a property that may be related to its effects on cell differentiation (Ko et al., 2004), neurotrophin expression (Féron et al., 2005), intracellular calcium signaling (Brewer et al., 2006), neurotransmitter release and synthesis (Kesby et al., 2017), and anti-inflammatory and antioxidant pathways (McCann and Ames, 2008; Cui et al., 2019). Therefore, hypovitaminosis D impairs the expression of several molecular targets involved in these cellular events (DeLuca et al., 2013; Kouba et al., 2022).

The prominent role of vitamin D in central nervous system (CNS) homeostasis suggests that deficiency of this vitamin may also be associated with a variety of brain disorders. Indeed, studies have reported an association between hypovitaminosis D and an increased risk of Azheimer's disease (Annweiler et al., 2013), Parkinson's disease (Ogura et al., 2021), and major depressive disorder (MDD) (Parker et al., 2017) in adults. In addition, vitamin D has been shown to improve the symptoms and behavioral changes associated with these disorders and may be used as a therapeutic adjuvant and/or potential neuroprotective agent (Kouba et al., 2022, Kouba et al., 2023b; Pignolo et al., 2022). Given that Parkinson's disease, Alzheimer's disease, and MDD are associated with impairment of neurogenic and synaptogenic processes (Skaper et al., 2017; Levy et al., 2018; Zhang and Lu, 2021), this narrative review aims to highlight neuroplasticity-related mechanisms of vitamin D that may be associated with its neuroprotective effects.(What are the amounts?)

Late-life physical activity relates to brain tissue synaptic integrity markers in older adults

Now your doctor needs to get you recovered enough to do the exercise and create an EXACT PROTOCOL for the amount of exercise needed because you actually need synaptogenesis to recover from your stroke. Now comes the the chicken or egg question, which comes first? Do you need synaptogenesis to occur first so you can do the exercises or do you need to do the exercise to create synaptogenesis? Ask your doctor and not politely. She is supposed to know this crap for your recovery. No knowledge, call the president and ask when s/he will get competent persons in stroke.

 

 Synaptogenesis is the formation of synapses between neurons in the nervous system. 

The latest here:

Late-life physical activity relates to brain tissue synaptic integrity markers in older adults

Kaitlin Casaletto PhD, Alfredo Ramos-Miguel PhD, Anna VandeBunte BA, Molly Memel PhD, Aron Buchman MD, David Bennett MD, William Honer MD

First published: 07 January 2022

https://doi.org/10.1002/alz.12530

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Abstract

Introduction

Physical activity (PA) is widely recommended for age-related brain health, yet its neurobiology is not well understood. Animal models indicate PA is synaptogenic. We examined the relationship between PA and synaptic integrity markers in older adults.

Methods

Four hundred four decedents from the Rush Memory and Aging Project completed annual actigraphy monitoring (Mean visits = 3.5±2.4) and post mortem evaluation. Brain tissue was analyzed for presynaptic proteins (synaptophysin, synaptotagmin-1, vesicle-associated membrane proteins, syntaxin, complexin-I, and complexin-II), and neuropathology. Models examined relationships between late-life PA (averaged across visits), and timing-specific PA (time to autopsy) with synaptic proteins.

Results

Greater late-life PA associated with higher presynaptic protein levels (0.14 < β < 0.20), except complexin-II (β = 0.08). Relationships were independent of pathology but timing specific; participants who completed actigraphy within 2 years of brain tissue measurements showed largest PA-to-synaptic protein associations (0.32 < β < 0.38). Relationships between PA and presynaptic proteins were comparable across brain regions sampled.

Discussion

PA associates with synaptic integrity in a regionally global, but time-linked nature in older adults.(What does time-linked mean?)

 

Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke

Sounds useful, Now we just need a stroke leader to write up a provisional protocol on this. Exercise is already recommended for all stroke patients so I can see no downside on this.  But nothing will occur, all stroke patients are screwed until we finally get rehab protocols, NOT GUIDELINES.

Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke

 

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Pengyue Zhang, MD, Liqiang Yang, MS, Guangxiang Li, MS, ...

First Published November 2, 2020 Research Article 

https://doi.org/10.1177/1545968320969939

Article information

 

Abstract

Background

Agrin is a proteoglycan that aggregates nicotinic acetylcholine receptors (AChRs) on neuromuscular junctions and takes part in synaptogenesis in the development of the central nervous system. However, its effects on neural repair and synaptogenesis after stroke are still unclear.

Objective

This study aimed to investigate the effects of agrin on neural repair and synaptogenesis after stroke and the effects of exercise on this process in vivo and in vitro.

Methods

Exercise with gradually increased intensity was initiated at 1 day after middle cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological deficit scores and foot fault tests were used to assess the behavioral recovery. Western blotting, immunofluorescence, and electron microscopic images were used to detect the expression of agrin, synaptogenesis-related proteins, and synaptic density in vivo. In vitro, the ischemic neuron model was established via oxygen-glucose deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor were used to investigate the mechanism by which agrin promoted synaptogenesis.

Results

Exercise promoted behavioral recovery and this beneficial role was linked to the upregulated expression of agrin and increased synaptic density. Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB inhibitor downregulated the expression of agrin and hampered synaptogenesis in cultured neurons.

Conclusions

These results indicated that exercise post stroke improved the recovery of behavioral function after stroke. Synaptogenesis was an important and beneficial factor, and agrin played a critical role in this process and could be a potential therapeutic target for the treatment of stroke and other nervous system diseases.

Keywords agrin, stroke, synaptogenesis, exercise, molecular mechanism

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Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action

I hold zero hope that this paper has protocols on the amounts you should be taking to kickstart neuroplasticity. 

 Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action

 Natalia Cichon 1,*, Joanna Saluk-Bijak 2 , Leslaw Gorniak 1 , Lukasz Przyslo 3 and Michal Bijak 1 1 Biohazard Prevention Center, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; leslaw.gorniak@biol.uni.lodz.pl (L.G.); michal.bijak@biol.uni.lodz.pl (M.B.) 2 Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; joanna.saluk@biol.uni.lodz.pl 3 Department of Developmental Neurology and Epileptology, Research Institute of Polish Mother’s Memorial Hospital, Rzgowska 281/289, 93-338 Lodz, Poland; lukasz.przyslo@iczmp.edu.pl * Correspondence: natalia.cichon@biol.uni.lodz.pl; Tel.: +48-42-635-43-36 Received: 26 September 2020; Accepted: 21 October 2020; Published: 23 October 2020


 

Abstract: 

Neuroplasticity is a complex physiological process occurring in the brain for its entire life. However, it is of particular importance in the case of central nervous system (CNS) disorders. Neurological recovery largely depends on the ability to reestablish the structural and functional organization of neurovascular networks, which must be pharmacologically supported. For this reason, new forms of therapy are constantly being sought. Including adjuvant therapies in standard treatment may support the enhancement of repair processes and restore impaired brain functions. The common hallmark of nerve tissue damage is increased by oxidative stress and inflammation. Thus, the studies on flavonoids with strong antioxidant and anti-inflammatory properties as a potential application in neuro intervention have been carried out for a long time. However, recent results have revealed another important property of these compounds in CNS therapy. Flavonoids possess neuroprotective activity, and promote synaptogenesis and neurogenesis, by, among other means, inhibiting oxidative stress and neuroinflammation. This paper presents an overview of the latest knowledge on the impact of flavonoids on the plasticity processes of the brain, taking into account the molecular basis of their activity

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex

Increased BDNF signaling and synaptogenesis sound wonderful for stroke recovery.  WHOM THE HELL  is going to do followup research on those two items in humans? I want exact names. Since we have NO STROKE LEADERSHIP, nothing will occur. You are fucking screwed as a stroke survivor.  You can't do this on your own, that would be practicing medicine without a license. 

Cannabidiol Induces Rapid and Sustained Antidepressant-Like Effects Through Increased BDNF Signaling and Synaptogenesis in the Prefrontal Cortex

• Amanda J. Sales,
• Manoela V. Fogaça,
• Ariandra G. Sartim,
• Vitor S. Pereira,
• Gregers Wegener,
• Francisco S. Guimarães &
• Sâmia R. L. Joca 

Molecular Neurobiology volume 56, pages1070–1081(2019)Cite this article

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Abstract

Currently available antidepressants have a substantial time lag to induce therapeutic response and a relatively low efficacy. The development of drugs that addresses these limitations is critical to improving public health. Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is a promising compound since it shows large-spectrum therapeutic potential in preclinical models and humans. However, its antidepressant properties have not been completely investigated. Therefore, the aims of this study were to investigate in male rodents (i) whether CBD could induce rapid and sustained antidepressant-like effects after a single administration and (ii) whether such effects could be related to changes in synaptic proteins/function. Results showed that a single dose of CBD dose-dependently induced antidepressant-like effect (7–30 mg/kg) in Swiss mice submitted to the forced swim test (FST), 30 min (acute) or 7 days (sustained) following treatment. Similar effects were observed in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rats and the learned helplessness (LH) paradigm using Wistar rats. The acute antidepressant effects (30 min) were associated with increased expression of synaptophysin and PSD95 in the medial prefrontal cortex (mPFC) and elevated BDNF levels in both mPFC and hippocampus (HPC). CBD also increased spine density in the mPFC after 30 min, but not 7 days later. Intracerebroventricular injection of the TrkB antagonist, K252a (0.05 nmol/μL), or the mTOR inhibitor, rapamycin (1 nmol/μL), abolished the behavioral effects of CBD. These results indicate that CBD induces fast and sustained antidepressant-like effect in distinct animal models relevant for depression. These effects may be related to rapid changes in synaptic plasticity in the mPFC through activation of the BDNF-TrkB signaling pathway. The data support a promising therapeutic profile for CBD as a new fast-acting antidepressant drug.

Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the prefrontal cortex of male and female rats

Don't do this. This will never have followup research in humans. 

Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the prefrontal cortex of male and female rats

View ORCID ProfileShirelle X. Liu, Mari S. Gades, Andrew H. Harris, Phu V. Tran, Jonathan C. Gewirtz

doi: https://doi.org/10.1101/2020.02.26.966416

This article is a preprint and has not been certified by peer review [what does this mean?].

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Abstract

Background Opioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied.

Methods We employed Next-Generation RNA-sequencing (RNA-seq) to investigate changes in gene expression in adult male and female rats’ prefrontal cortex (PFC) following daily injection of morphine (5.0 mg/kg) for 10 days. Ingenuity Pathway Analysis (IPA) was used to analyze affected molecular pathways, gene networks, and associated regulatory factors.

Results 90% of differentially expressed genes (DEGs) were upregulated in both males and females, with a 35% overlap between sexes. A substantial number of DEGs play roles in synaptic signaling and neuroplasticity. Although broadly similar, some differences were revealed in the gene ontology networks enriched in females and males (e.g., the endocannabinoid pathway in females and neuroinflammation in males).

Conclusions Our results cohere with findings from previous studies based on a priori gene selection, while identifying broader gene networks activated by repeated opioid exposure. Our results also reveal novel genes and molecular pathways that are upregulated by repeated morphine exposure.

Footnotes

• Role of Funding Source: This work was supported by grants from the Engdahl Family Research Fund and the Office of the Vice President for Research, University of Minnesota, and by T32 DA007097.

Copyright 

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke

So maybe statins aren't that bad.  But it doesn't say what dose is needed, so get your doctor to find that out.  Yes, this is in rats but your stroke medical professionals should have found out that answer for humans. At least if they were competent. 17 years to become competent in that, that should be enough time for even the slowest.

Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke

Jieli Chen MD

Zheng Gang Zhang MD, PhD

Yi Li MD

Ying Wang MD

Lei Wang MD

Hao Jiang PhD

Chenling Zhang BS

Mei Lu PhD

Mark Katakowski BS

Carolyn S. Feldkamp PhD

Michael Chopp PhD

First published: 27 May 2003

https://doi.org/10.1002/ana.10555

Citations: 383

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We demonstrate that the 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors atorvastatin and simvastatin enhance functional outcome and induce brain plasticity when administered after stroke to rats. With atorvastatin treatment initiated 1 day after stroke, animals exhibited significant increases in vascular endothelial growth factor, cyclic guanosine monophosphate, angiogenesis, endogenous cell proliferation and neurogenesis, and an increase in the synaptic protein, synaptophysin. Atorvastatin‐induced angiogenesis in a tube formation assay was reduced by an antibody against the vascular endothelial growth factor receptor 2 (FIK‐1) and by the nitric oxide synthase inhibitor, N‐mono‐methyl‐L‐arginine (L‐NAME). Atorvastatin also induced phosphorylation of Akt and Erk in cultured primary cortical neurons. These data indicate that atorvastatin induced brain plasticity and has neurorestorative activity after experimental stroke. Ann Neurol 2003

14 Powerful Ways to Form New Synapses in the Brain

Is your doctor suggesting any of these to help your stroke recovery? Unless they are written as protocols, they are completely fucking useless in guaranteeing new synapses. Screaming at your incompetent? doctor may be required!

14 Powerful Ways to Form New Synapses in the Brain 

January 28, 2018 Jordan Fallis

1. Omega-3 Fatty Acids, Uridine and Choline

2. Low Level Laser Therapy

3. Bacopa

4. Exercise

5. Magnesium Threonate

6. Intermittent Fasting

7. Ginkgo Biloba

8. Motor Learning

9. Resveratrol

10. Piracetam

11. Quercetin

12. Intranasal Insulin

13. Progesterone

14. Antioxidant Nutrients

15. BONUS: 4 Things to Avoid

Details at link. You might want to ask your doctor about these. 

The Rewiring Brain - Chapter 3 – Structural Neural Plasticity During Stroke Recovery

You'll have to ask your doctor what stroke protocols came out of this book that help you get to 100% recovery.
https://www.sciencedirect.com/science/article/pii/B9780128037843000032

• Kimberly Gerrow¹,
• Craig E. Brown^{1, 2}

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https://doi.org/10.1016/B978-0-12-803784-3.00003-2

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---

Abstract

Focal ischemic stroke is in many ways reminiscent of an earthquake. Its effects on structure and function are immediate and most strongly experienced by those closest to it. During the initial stages, a neurons’ first priority is survival and there are remarkable imaging studies to show how resilient neuronal structure can be in the face of death. For the neurons that do survive, they must overcome waves of aberrant electrical activity, inflammation and other insults that reverberate for days after stroke(neuronal cascade of death), and further strip them of their synaptic connections. Once these stroke aftershocks have subsided, neurons must rebuild and establish new and meaningful lines of communication. Indeed, experimental data show that dendritic spine formation, axonal growth, and synaptogenesis surge in the weeks that follow stroke. This period of growth correlates with the emergence of new receptive fields and patterns of brain activity that are considered essential for recovering functions lost to stroke. This chapter will highlight important experimental advances in this field, provide the most up-to-date perspective on structural neuronal plasticity in the stroke-affected brain, and define controversies for future studies to resolve.

Keywords

• Stroke;
• dendrites;
• dendritic spines;
• axonal sprouting;
• plasticity;
• repair

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Plant compound found in spices and herbs increases brain connections

Do not do anything with this. You know how dangerous it is to eat foods not prescribed by your doctor. You'll have to wait 50 years before a stroke diet protocol is created. Maybe your  grandchildren will benefit after their stroke. But only if you pay it forward by repurposing the existing stroke associations to actually be for survivors.

The readable article here:

Plant compound found in spices and herbs increases brain connections 

Parsley, celery and chamomile tea are the most common sources of apigenin

 

The research it is based upon here:

 

Commitment of human pluripotent stem cells to a neural lineage is induced by the pro-estrogenic flavonoid apigenin

Cleide S. Souza^1†, Bruna S. Paulsen^1†, Sylvie Devalle¹, Silvia Lima Costa², Helena L. Borges¹ and Stevens K. Rehen^1,3*

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Keywords adult stem cell apigenin bone targeting. cell transplantation cellular therapy contractility double blind peer review process endothelial cell estrogen receptors eye disease feto-maternal chimerisms gene therapy glycation neural induction osteogenesis imperfecta reaggregation renal retinal pigment epithelium retinoic acid receptors self-organization synapses

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¹Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; ²Institute of Health Sciences, Federal University of Bahia, Bahia, Brazil; ³D’Or Institute of Research and Education (IDOR), Rio de Janeiro, Brazil

Abstract

Flavonoids are polyphenolic compounds that are ubiquitous in plants and have biological effects on cancer cells and other cell types. In particular, apigenin (API) has been shown to bind to estrogen receptors, which affect the development, maturation, function, and plasticity of the nervous system. The aim of this study was to investigate the effects of 4′,5,7-trihydroxyflavone (API) upon the neural differentiation of human pluripotent stem cells. Treatment of both human embryonic stem cells and human induced pluripotent stem cells with API increased the number of nestin (NES⁺) neural progenitor cells compared to untreated controls. API also induced the expression of neuronal markers, such as β-tubulin-III (TUBB3), microtubule-associated protein 2 (MAP2), polysialylated-neural cell adhesion molecule (PSA-NCAM), synapsin 1 (SYN1), neurofilament (NEF), choline acetyltransferase (CHAT), glutamate decarboxylase (GAD1), and parvalbumin (PVALB) proteins. Antagonists of estrogen receptors (ESR1 and ESR2) suppressed the effects of API. API-induced differentiation was followed by increased expression of retinoic acid (RA) receptors (RARA and RARB) and retinoic X receptor (RXR) G, but not RARG1 or RXRB. Neural differentiation induced by API was drastically reduced by the inhibition of RARs. In addition, API also increased synaptogenesis in RA-differentiated neurons. These findings suggest that API induces neural differentiation of human pluripotent stem cells through estrogen receptor and RAR signaling and improves their functional differentiation into neurons.
Keywords: apigenin; neural induction; estrogen receptors; retinoic acid receptors; synapses

In context

Human embryonic stem cells can give rise to any cell type of the human body. One of the main challenges in regenerative biology is to drive these cells to become specific cells types, preferentially by adopting simple and less expensive approaches. Here we show that, by simply adding a plant compound called apigenin to human pluripotent stem cells, they become neurons after a few days. We also observed that neurons could make more sophisticated connections among themselves after treatment with this natural compound. This observation suggests that flavonoids derived from plants can be used as a tool for the production of neurons in a dish. Moreover, since flavonoids are present at high amounts in some foods, we can speculate that a diet rich in flavonoids may influence the formation of neurons and the way they communicate within the brain.

Citation: Advances in Regenerative Biology 2015, 2: 29244 - http://dx.doi.org/10.3402/arb.v2.29244

Experience with the “Good” Limb Induces Aberrant Synaptic Plasticity in the Perilesion Cortex after Stroke

Well if using the 'good' side impairs recovery of the 'bad' side then all survivors are totally fucking screwed in trying to get 100% recovery.  Which to me means we need to stop a lot of the damage in the first place by stopping the neuronal cascade of death.
http://www.jneurosci.org/content/35/22/8604.short?
What is your doctors solution to get around this problem? I don't know is not an ok answer.

1. Soo Young Kim¹,
2. Rachel P. Allred²,*,
3. DeAnna L. Adkins⁴,*,
4. Kelly A. Tennant³,
5. Nicole A. Donlan²,
6. Jeffrey A. Kleim⁵, and
7. Theresa A. Jones²,³

+Show Affiliations

1. Author contributions: S.Y.K., R.P.A., D.L.A., J.A.K., and T.A.J. designed research; S.Y.K., R.P.A., D.L.A., K.A.T., N.A.D., and T.A.J. performed research; J.A.K. contributed unpublished reagents/analytic tools; S.Y.K., R.P.A., D.L.A., and T.A.J. analyzed data; S.Y.K. and T.A.J. wrote the paper.
2. ↵*R.P.A. and D.L.A. contributed equally to this work.

1. The Journal of Neuroscience, 3 June 2015, 35(22): 8604-8610; doi: 10.1523/JNEUROSCI.0829-15.2015

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Abstract

Following unilateral stroke, the contralateral (paretic) body side is often severely impaired, and individuals naturally learn to rely more on the nonparetic body side, which involves learning new skills with it. Such compensatory hyper-reliance on the “good” body side, however, can limit functional improvements of the paretic side. In rats, motor skill training with the nonparetic forelimb (NPT) following a unilateral infarct lessens the efficacy of rehabilitative training, and reduces neuronal activation in perilesion motor cortex. However, the underlying mechanisms remain unclear. In the present study, we investigated how forelimb movement representations and synaptic restructuring in perilesion motor cortex respond to NPT and their relationship with behavioral outcomes. Forelimb representations were diminished as a result of NPT, as revealed with intracortical microstimulation mapping. Using transmission electron microscopy and stereological analyses, we found that densities of axodendritic synapses, especially axo-spinous synapses, as well as multiple synaptic boutons were increased in the perilesion cortex by NPT. The synaptic density was negatively correlated with the functional outcome of the paretic limb, as revealed in reaching performance. Furthermore, in animals with NPT, there was dissociation between astrocytic morphological features and axo-spinous synaptic density in perilesion motor cortex, compared with controls. These findings demonstrate that skill learning with the nonparetic limb following unilateral brain damage results in aberrant synaptogenesis, potentially of transcallosal projections, and this seems to hamper the functionality of the perilesion motor cortex and the paretic forelimb.