Human Milk Oligosaccharide 2′-Fucosyllactose Reduces Neurodegeneration in Stroke Brain

 Good luck trying to find a source for human milk. Or maybe you want your doctor to increase bromodeoxyuridine (BrdU) another way.  Your doctor should be fluent in everything in this research.

• BrdU (26 posts to May 2011)

 Human Milk Oligosaccharide 2′-Fucosyllactose Reduces Neurodegeneration in Stroke Brain

• Kou-Jen Wu,
• Yun-Hsiang Chen,
• Eun-Kyung Bae,
• YoungHa Song,
• WonKi Min &
• Seong-Jin Yu 

Translational Stroke Research (2020)Cite this article

Abstract

2′-Fucosyllactose (2’-FL) is a major oligosaccharide in human milk and is present at trace levels in cow milk. 2’-FL reduces inflammation in the gastrointestinal tract. Its action in the central nervous system has not been well characterized. The purpose of this study is to determine 2’-FL-mediated neural protection and repair in culture and stroke brain. In rat primary cortical neuronal cultures, 2’-FL significantly antagonized N-methyl-D-aspartate (NMDA) or glutamate-mediated changes in ATP production, MAP2 immunoreactivity, and TUNEL. The influx of Ca⁺⁺ (Ca⁺⁺i) was examined in primary cortical neurons expressing GCaMP5, an endogenous calcium probe. NMDA increased Ca⁺⁺i; 2’-FL significantly attenuated this reaction. In a rat middle cerebral artery occlusion model of stroke, we found that intracerebroventricular pretreatment or oral posttreatment with 2’-FL significantly reduced brain infarction, mitigated microglial activation, improved locomotor activity, and upregulated brain-derived neurotrophic factor (BDNF) expression. Post-stroke delivery of 2’-FL increased bromodeoxyuridine (BrdU) labeling in the perilesioned area. These BrdU cells co-expressed NeuN, or nestin, or GFAP. Using subventricular Matrigel cultures, we demonstrated that 2’-FL increased cell migration from subventricular zone explant. This response was reduced by anti-BDNF blocking antibody. In conclusion, our data suggest that 2’-FL has neuroprotective action through inhibition of Ca⁺⁺i, inflammation, and apoptosis. Posttreatment with 2’-FL facilitates neural repair in stroke brain.

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Hydrogen sulfide improves spatial memory impairment via increases of BDNF expression and hippocampal neurogenesis following early postnatal alcohol exposure

Hydrogen sulfide research back to 2013 proved helpful for survivors and you do want BDNF. 8 posts on it here.  But shit once again nothing seems to have been done that might actually help stroke survivors. I blame our fucking failures of stroke associations, great at doing nothing for survivors. WHAT IS YOUR DOCTOR'S PROTOCOL FOR PROMOTING BDNF?

Hydrogen sulfide improves spatial memory impairment via increases of BDNF expression and hippocampal neurogenesis following early postnatal alcohol exposure

Author links open overlay panelFahimehMohseni^aFarzanehBagheri^bRahelehRafaiee^cPirastehNorozi^dMehdiKhaksari^e

https://doi.org/10.1016/j.physbeh.2019.112784Get rights and content

Highlights

•

Hydrogen sulfide improve spatial memory impairment in a model of fetal alcohol spectrum disorders.

•

Hydrogen sulfide reduced apoptotic cell death in model of fetal alcohol spectrum disorders

•

Hydrogen sulfide increased neurogenesis in model of fetal alcohol spectrum disorders

•

Hydrogen sulfide increased of BDNF expression in model of fetal alcohol spectrum disorders

Abstract

According to experimental and clinical findings, fetal brain development may be interrupted by maternal alcohol consumption during pregnancy. Adult hippocampal neurogenesis is thought to play a role in cognition function (i.e. learning and memory). Recent evidence suggests that ethanol administration causes major apoptotic neurodegeneration in many regions of the rats’ developing brain during the synaptogenesis period. Based on the recent studies, H₂S improve learning and memory via increased neurogenesis and antiapoptotic mechanisms in different animal models. In this study, we aimed to evaluate the protective effects of hydrogen sulfide on alcohol-induced memory impairment, hippocampus neurogenesis and neuronal apoptosis in rat pups with postnatal ethanol exposure.

Administration of ethanol to male rat pups was performed through intragastric intubation on postnatal days 2-10. The pups were administered 1 mg/kg of NaHS (H₂S donor) on postnatal days 2-10. For examining the spatial memory, Morris water maze test was carried out 36 days after birth. Following the behavioral test, immunohistochemical staining was performed to evaluate the expression levels of BrdU, BDNF and Apoptotic cell death was detected by TUNEL staining.

Hydrogen sulfide (H₂S) treatment could significantly improve spatial memory impairment (P< 0.05) and significantly increase the expression of BrdU and BDNF in dentate gyrus area (P< 0.05). It also decreased positive TUNEL cells, compared with the ethanol group (P< 0.01).

Based on the findings, H₂S makes significant neuroprotective effects on Ethanol neurotoxicity due to its neurogenesis and anti-apoptotic activity.

Early Stroke Induces Long-Term Impairment of Adult Neurogenesis Accompanied by Hippocampal-Mediated Cognitive Decline

There might be something here, but I don't know. 

Early Stroke Induces Long-Term Impairment of Adult Neurogenesis Accompanied by Hippocampal-Mediated Cognitive Decline

 Carolin Kathner-Schaffert 1, Lina Karapetow 1, Madlen Günther 1, Max Rudolph 1, Mahmoud Dahab 1, Eileen Baum 1, Thomas Lehmann 2, Otto W. Witte 1, Christoph Redecker 1, Christian W. Schmeer 1 and Silke Keiner 1,* 1 Hans-Berger Department of Neurology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany; Carolin.Kathner-Schaffert@med.uni-jena.de (C.K.-S.); Lina.Karapetow@med.uni-jena.de (L.K.); Madlen.Guenther@med.uni-jena.de (M.G.); Max.Rudolph@uni-jena.de (M.R.); Mahmoud.Mohamed@med.uni-jena.de (M.D.); Eileen.Baum@noldus.com (E.B.); Otto.Witte@med.uni-jena.de (O.W.W.); Christoph.Redecker@klinikum-lippe.de (C.R.); Christian.Schmeer@med.uni-jena.de (C.W.S.) 2 Institute of Medical Statistics and Computer Science, University Hospital Jena, Friedrich Schiller University Jena, 07743 Jena, Germany; Thomas.Lehmann@med.uni-jena.de * Correspondence: silke.keiner@med.uni-jena.de; Tel.: +49-364-1932-5914
Received: 14 October 2019; Accepted: 12 December 2019; Published: 17 December 2019






Abstract: 

Stroke increases neurogenesis in the adult dentate gyrus in the short term, however, long-term effects at the cellular and functional level are poorly understood. Here we evaluated the impact of an early stroke lesion on neurogenesis and cognitive function of the aging brain. We hypothesized that a stroke disturbs dentate neurogenesis during aging correlate with impaired flexible learning. To address this issue a stroke was induced in 3-month-old C57Bl/6 mice by a middle cerebral artery occlusion (MCAO). To verify long-term changes of adult neurogenesis the thymidine analogue BrdU (5-Bromo-20-deoxyuridine) was administrated at different time points during aging. One and half months after BrdU injections learning and memory performance were assessed with a modified version of the Morris water maze (MWM) that includes the re-learning paradigm, as well as hippocampus-dependent and -independent search strategies. After MWM performance mice were transcardially perfused. To further evaluate in detail the stroke-mediated changes on stem- and progenitor cells as well as endogenous proliferation nestin-green-fluorescent protein (GFP) mice were used. Adult nestin-GFP mice received a retroviral vector injection in the hippocampus to evaluate changes in the neuronal morphology. At an age of 20 month the nestin-GFP mice were transcardially perfused after MWM performance and BrdU application 1.5 months later. The early stroke lesion significantly decreased neurogenesis in7.5-and 9-month-old animals and also endogenous proliferation in the latter group. Furthermore, immature double cortin (DCX)-positive neurons were reduced in 20-month-old nestin-GFP mice after lesion. All MCAO groups showed an impaired performance in the MWM and mostly relied on hippocampal independent search strategies. These findings indicate that an early ischemic insult leads to a dramatical decline of neurogenesis during aging that correlates with a premature development of hippocampal dependent deficits. Our study supports the notion that an early stroke might lead to long-term cognitive deficits as observed in human patients after lesion.

Korean Red Ginseng enhances neurogenesis in the subventricular zone of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated mice

Yes this is in mice and for Parkinsons but WHOM do we go to to get this tested in humans with stroke? 

Korean Red Ginseng enhances neurogenesis in the subventricular zone of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated mice

Sun Ryu¹, Hyongjun Jeon², Sungtae Koo² and Seungtae Kim^2*

• ¹Korean Medicine Research Center for Healthy Aging, Pusan National University, South Korea
• ²Department of Korean Medical Science, Pusan National University, South Korea

Modulation of endogenous neurogenesis would have a significant impact on future therapeutic strategies for neurodegenerative diseases. Recent studies have suggested that the enhancement of adult neurogenesis can be helpful in the treatment of Parkinson’s disease (PD). In this study, we investigated augmentative effects of Korean Red Ginseng (KRG) on neurogenesis in the subventricular zone (SVZ) of a PD mouse model. Male eight-week-old C57BL/6 mice were injected with vehicle or 20 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) four times at 2-h intervals. After the final injection, they were administrated vehicle or 100 mg/kg of Korean Red Ginseng extract and injected intraperitoneally with 50 mg/kg of 5’-bromo-2’-deoxyuridine-monophosphate (BrdU) once a day for 14 consecutive days. After the last pole test, dopaminergic neuronal survival in the nigrostriatal pathway, cell proliferation in the SVZ and mRNA expressions of neurotrophic factors and dopamine receptors in the striatum were evaluated. KRG administration suppressed MPTP-induced dopaminergic neuronal death in the nigrostriatal pathway, increased the number of BrdU- and BrdU/doublecortin-positive cells in the SVZ and enhanced the expressions of proliferation cell nuclear antigen, brain derived neurotrophic factor, glial cell derived neurotrophic factor, cerebral dopamine neurotrophic factor, ciliary neurotrophic factor, dopamine receptor D3 and D5 mRNAs. These results suggest that KRG administration augments neurogenesis in the SVZ of a PD mouse model.

Keywords: Parkinson's disease (PD), Korean red ginseng (KRG), Neurogenesis, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), subventricular zone (SVZ)

Received: 29 Jun 2018; Accepted: 18 Oct 2018.

Edited by:
Seung-Nam Kim, Dongguk University Seoul, South Korea

Reviewed by:
Songhee Jeon, Chonnam National University Medical School, South Korea
Ji-Yeun Park, Daejeon University, South Korea  

Copyright: © 2018 Ryu, Jeon, Koo and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Effects of Scopolamine and Melatonin Cotreatment on Cognition, Neuronal Damage, and Neurogenesis in the Mouse Dentate Gyrus

Mouse, not human, so of course followup is needed. Save your pennies so you can hire your own researchers on this, it is the only way followup will get done.  Or GoFundMe.
https://link.springer.com/article/10.1007/s11064-017-2455-x

• Authors
• Authors and affiliations

• Bai Hui Chen
• Ji Hyeon Ahn
• Joon Ha Park
• Soo Young Choi
• Yun Lyul Lee
• Il Jun Kang
• In Koo Hwang
• Tae-Kyeong Lee
• Bich-Na Shin
• Jae-Chul Lee
• Seongkweon Hong
• Yong Hwan Jeon
• Myoung Cheol Shin
• Jun Hwi Cho
• Moo-Ho WonEmail author
• Young Joo LeeEmail author

• Bai Hui Chen
  • 1
• Ji Hyeon Ahn
  • 2
• Joon Ha Park
  • 2
• Soo Young Choi
  • 2
• Yun Lyul Lee
  • 3
• Il Jun Kang
  • 4
• In Koo Hwang
  • 5
• Tae-Kyeong Lee
  • 6
• Bich-Na Shin
  • 6
• Jae-Chul Lee
  • 6
• Seongkweon Hong
  • 7
• Yong Hwan Jeon
  • 8
• Myoung Cheol Shin
  • 9
• Jun Hwi Cho
  • 9
• Moo-Ho Won
  • 6
  Email authorView author's OrcID profile
• Young Joo Lee
  • 10
  Email author

1. 1.Department of Histology and Embryology, Institute of NeuroscienceWenzhou Medical UniversityWenzhouPeople’s Republic of China
2. 2.Department of Biomedical Science and Research Institute for Bioscience and BiotechnologyHallym UniversityChuncheonSouth Korea
3. 3.Department of Physiology, College of Medicine, and Institute of Neurodegeneration and NeuroregenerationHallym UniversityChuncheonSouth Korea
4. 4.Department of Food Science and NutritionHallym UniversityChuncheonSouth Korea
5. 5.Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
6. 6.Department of Neurobiology, School of MedicineKangwon National UniversityChuncheonSouth Korea
7. 7.Department of Surgery, School of MedicineKangwon National UniversityChuncheonSouth Korea
8. 8.Department of Radiology, School of MedicineKangwon National University, Kangwon National University HospitalChuncheonSouth Korea
9. 9.Department of Emergency Medicine, and Institute of Medical Sciences, Kangwon National University Hospital, School of MedicineKangwon National UniversityChuncheonSouth Korea
10. 10.Department of Emergency Medicine, Seoul Hospital, College of MedicineSooncheonhyang UniversitySeoulSouth Korea

Original Paper

First Online: 19 December 2017

• 13 Downloads

Abstract

It has been demonstrated that melatonin plays important roles in memory improvement and promotes neurogenesis in experimental animals. We examined effects of melatonin on cognitive deficits, neuronal damage, cell proliferation, neuroblast differentiation and neuronal maturation in the mouse dentate gyrus after cotreatment of scopolamine (anticholinergic agent) and melatonin. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected for 2 and/or 4 weeks to 8-week-old mice. Scopolamine treatment induced significant cognitive deficits 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly improved spatial learning and short-term memory impairments. Two and 4 weeks after scopolamine treatment, neurons were not damaged/dead in the dentate gyrus, in addition, no neuronal damage/death was shown after cotreatment of scopolamine and melatonin. Ki67 (a marker for cell proliferation)- and doublecortin (a marker for neuroblast differentiation)-positive cells were significantly decreased in the dentate gyrus 2 and 4 weeks after scopolamine treatment, however, cotreatment of scopolamine and melatonin significantly increased Ki67- and doublecortin-positive cells compared with scopolamine-treated group. However, double immunofluorescence for NeuN/BrdU, which indicates newly-generated mature neurons, did not show double-labeled cells (adult neurogenesis) in the dentate gyrus 2 and 4 weeks after cotreatment of scopolamine and melatonin. Our results suggest that melatonin treatment recovers scopolamine-induced spatial learning and short-term memory impairments and restores or increases scopolamine-induced decrease of cell proliferation and neuroblast differentiation, but does not lead to adult neurogenesis (maturation of neurons) in the mouse dentate gyrus following scopolamine treatment.

Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells

Sounds promising. You will have to have your doctor contact their stroke research partners to get this tested in humans. If they don't have partners your stroke department head is incompetent along with your stroke hospital president.  With no partners they are just inert and useless doctors,

WAITING FOR SOMEONE ELSE TO SOLVE THE PROBLEM?

I could see significant problems getting through the skull to actually affect the brain itself. But that is for your doctor and researchers to solve. 

Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells

Author links open overlay panelLuodanYang^abDonovanTucker^bYanDong^bChongyunWu^aYujiaoLu^bYongLi^bJuanZhang^bTimon Cheng-YiLiu^aQuanguangZhang;

https://doi.org/10.1016/j.expneurol.2017.10.013Get rights and content

Highlights

•

PBM alleviates behavioral deficits after PT stroke.

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PBM decreases cortical infarct size and increases neuronal survival.

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PBM promotes cortical neurogenesis after PT stroke.

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PBM inhibits local inflammatory status and promotes mitochondrial function.

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PBM promotes proliferation and differentiation of neuroprogenitor cells.

Abstract

Recent work has indicated that photobiomodulation (PBM), also known as low-level laser/light therapy (LLLT), may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808 nm, 350 mW/cm², total 294 J at scalp level) was applied on the infarct injury area (1.8 mm anterior to the bregma and 2.5 mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50 mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.

Indomethacin increases neurogenesis across age groups and improves delayed probe trial difference scores in middle-aged rats

I expect our researchers to start up a clinical trial shortly on this. Although the water-maze test for stroke humans might be deadly. 
http://journal.frontiersin.org/article/10.3389/fnagi.2017.00280/abstract

James A. McGuiness¹, Rachel B. Scheinert¹, Aditya Asokan¹, Vivien-Charlott Stadler¹, Chris S. Lee¹, Asha Rani², Ashok Kumar², Thomas C. Foster² and Brandi K. Ormerod^{1, 2*}

• ¹J. Crayton Pruitt Family Dept of Biomedical Engineering, University of Florida, United States
• ²Neuroscience Deparment and McKnight Brain Institute, University of Florida, United States

We tested whether indomethacin or rosiglitazone treatment could rejuvenate spatial ability and hippocampal neurogenesis in aging rats. Young (4 mo; n = 30), middle-aged (12 mo; n = 31) and aged (18 mo; n = 31) male Fischer 344 rats were trained and then tested in a rapid acquisition water maze task and then fed vehicle (500µl strawberry milk), indomethacin (2.0mg/ml) or rosiglitazone (8.0mg/ml) twice daily for the remainder of the experiment. A week after drug treatment commenced, the rats were given 3 daily BrdU (50mg/kg) injections to test whether age-related declines in neurogenesis were reversed. One week after the final BrdU injection (~2.5 weeks after the 1st water maze session), the rats were trained to a find novel hidden water maze platform location, tested on 15min and 24h probe trials and then killed 24h later. During the first water maze session, young rats outperformed aged rats but all rats learned information about the hidden platform location. Middle-aged and aged rats exhibited better memory probe trial performances than young rats in the 2nd water maze session and indomethacin improved memory probe trial performances on the 2nd versus 1st water maze session in middle-aged rats. Middle-aged rats with more new neurons had fewer phagocytic microglia and exhibited better hidden platform training trial performances on the 2nd water maze session. Regardless of age, indomethacin increased new hippocampal neuron numbers and both rosiglitazone and indomethacin increased subependymal neuroblasts/neuron densities. Taken together, our results suggest the feasibility of studying the effects of longer-term immunomodulation on age-related declines in cognition and neurogenesis.

dl-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats

Your doctor and hospital better get cracking on followup research in humans for this. With 10s of thousands of hospitals and doctors out there at least one should be able to solve this into a translational result.  But you know that will never occur, it hasn't occurred in the last 50 years it won't miraculously start occurring now. 

dl-3-n-butylphthalide promotes neuroplasticity and motor recovery in stroke rats

• Yefei Sun^a,
• Xi Cheng^b,
• Huibin Wang^b,
• Xiaopeng Mu^b,
• Yifan Liang^b,
• YuJia Luo^b,
• Huiling Qu^c,
• Chuansheng Zhao^{b, ,}

 Show more

https://doi.org/10.1016/j.bbr.2017.04.039

Get rights and content

---

Highlights

•

dl-NBP promoted the behavioral performance after cerebral ischemia in rats.

•

dl-NBP improved the behavioral recovery possibly by increasing neurogenesis, axonal regeneration and synapse formation.

•

The axonal regeneration promoted by dl-NBP may be mediated through the Nogo-A/NgR and RhoA/ROCK pathway.

---

Abstract

Backgrounds and aims

Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer’s disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia.

Methods

Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70 mg/kg dl-NBP by oral gavage for two weeks. Biotinylated dextran amine (BDA) was injected into the contralateral sensorimotor cortex on day 14 after ischemia to trace the sprouting of corticospinal tract (CST) fibers into the denervated cervical spinal cord. The expressions of Nogo-A, Nogo-R, Rho-A, and ROCK in the perilesional cortex, the expressions of BDA, PSD-95, and vGlut1 in the denervated spinal cord, 5-bromo-20-deoxyuridine (BrdU)/DCX-positive cells in the subventricular zone (SVZ) of the injured hemisphere were detected by immunofluorescence. The rats’ behavioral abilities were measured on postoperative days 30–32 in the beam-walking, cylinder and sticky label tests.

Results

dl-NBP treatment significantly increased the number and length of crossing CST fibers, enhanced significantly the expression levels of synapse-associated proteins including PSD95 and VGlut-1 in the denervated cervical spinal cord, elevated the number of BrdU+/DCX+ cells in SVZ, and reduced markedly those of Rho-A+, ROCK+, Nogo-A+ and Nogo-R+ cells in perilesional cortex. In addition, dl-NBP improved the behavioral performance of the ischemic rats.

Conclusion

dl-NBP enhanced the behavioral recovery after cerebral ischemia in rats, possibly by increasing axonal growth and neurogenesis.

Keywords

• Axonal growth;
• dl-NBP;
• Neurogenesis;
• Stroke

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Correspondence to: No.155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, China.

© 2017 Elsevier B.V. All rights reserved.

Abstract WP118: Docosahexaenoic Acid Provides Neuroprotection by Increasing Neurogenesis After Experimental Stroke

These always seem to need more followup to be useful rather than doing it right in the first place and doing some real research. Regardless, I bet your doctor does nothing with this information.
A. Because s/he never read it.
B. Because s/he could not be bothered to understand how to implement it in a protocol.
C. It is not my job. I am waiting for SOMEONE ELSE TO SOLVE THE PROBLEM. Namely 100% recovery for all my stroke patients.

Abstract WP118: Docosahexaenoic Acid Provides Neuroprotection by Increasing Neurogenesis After Experimental Stroke

Nicolas G Bazan, Larissa Khoutorova, Sung-Ha Hong, Hemant Menghani, Ludmila Belayev

Stroke. 2017;48:AWP118

• Article
• Info & Metrics

• Article
• Info & Metrics

Abstract

Introduction: Ischemic injury induces neurogenesis in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of dentate gyrus (DG), and it promotes the migration of neuroblasts, guided by blood vessels, into the ischemic damaged area. Recently, we have shown that docosahexaenoic acid (DHA; 22:6n-3) therapy improves functional and histological outcomes following experimental stroke. The objective, hence, is to determine whether DHA administration enhances endogenous neurogenesis after cerebral ischemia.

Methods: Twenty-one male SD rats were anesthetized with isoflurane and subjected to 2 h of middle cerebral artery occlusion (MCAo) by intraluminal filament. DHA (5 mg/kg, n=10) or saline (n=11) was administered intravenously at 3 h after onset of MCAo (n = 7-10 per group). BrdU was injected on days 4, 5 and 6. DCX (doublecortin), NeuN (a marker for mature neurons), ki-67 (marker for cell proliferation) have been used to test the proliferation, migration and differentiation of neural precursor cells. Behavioral tests were conducted on days 1, 2 and 3 and weeks 1 and 2. Immunohistochemistry with BrdU and ki-67, DCX or NeuN, and histopathology were performed on day 14.

Results: DHA-treated animals showed improved neurologic scores compared to the saline group during the two-week survival period. Total, cortical and subcortical infarct areas in the DHA-treated group were significantly attenuated at multiple bregma levels as well as total, cortical and subcortical infarct volumes by 42.4 %, by 47.5 %, and by 31.2 % compared to the vehicle-treated group. The number of BrdU⁺/ki-67⁺ cells in DHA-treated rats was increased in cortex by 88 %, SVZ by 40 % and DG by 270 % compared to saline-treated rats. DHA treatment increased the number of BrdU⁺/DCX⁺ cells in the cortex by 65 %, the SVZ by 29 % and the DG (by 58 %) compared to saline-treated group. In addition, the numbers of BrdU⁺/NeuN⁺ cells were increased in the cortex by 49 %, SVZ by 28 % and DG by 48% compared to vehicle treatment.

Conclusion: DHA increased neurogenesis by proliferation, differentiation and migration of neural stem cells in the DG, SVZ and peri-infarct area two weeks after ischemic stroke. In addition, DHA promoted neurobehavioral recovery and reduced infarct volume.

Myeloperoxidase inhibition increases neurogenesis after ischemic stroke

What protocol does your doctor have to increase your neurogenesis? How does s/he know that neurogenesis is working? Does your doctor know ONE DAMN THING ABOUT NEUROGENESIS?
http://jpet.aspetjournals.org/content/early/2016/08/22/jpet.116.235127.abstract

1. HyeonJu Kim1,
2. Ying Wei1,
3. Ji Yong Lee1,
4. Yue Wu1,
5. Yi Zheng1,
6. Michael A. Moskowitz2, and
7. John W. Chen1,*

+ Author Affiliations

1. ¹ MGH;
2. ² Massachusetts General Hospital

1. ↵^*Address correspondence to: jwchen@mgh.harvard.edu

Abstract

The relationship between inflammation and neurogenesis in stroke is currently not well understood. Focal ischemia enhances cell proliferation and neurogenesis in the neurogenic regions including the subventricular zone (SVZ), dentate gyrus (DG) as well as non-neurogenic striatum, cortex in the ischemic hemisphere. Myeloperoxidase (MPO) is a potent oxidizing enzyme secreted during inflammation by activated leukocytes and its enzymatic activity is highly elevated after stroke. In this study, we investigated whether inhibition of MPO activity by a specific irreversible inhibitor, 4-aminobenzoic acid hydrazide (ABAH) or MPO-/- mice can increase neurogenesis after transient middle cerebral artery occlusion (tMCAO) in mice. ABAH administration increased the number of proliferating 5-bromo-2' deoxyuridine (BrdU)-positive cells expressing markers for neural stems cells, astrocytes, neuroprogenitors (Nestin), and neuroblasts (doublecortin) in the ischemic SVZ, anterior SVZ (aSVZ), striatum and cortex. MPO inhibition also increased levels of brain-derived neurotrophic factor (BDNF), phospho-cAMP response element-binding protein (pCREB Ser133), acetylated H3 (AcH3), and NeuN to promote neurogenesis in the ischemic SVZ. ABAH treatment also increased chemokine CXC receptor 4 (CXCR 4) expression in the ischemic SVZ. MPO-deficient mice treated with vehicle or ABAH both showed similar effects on the number of BrdU+ cells in the ischemic hemisphere, demonstrating that ABAH is specific to MPO. Taken together, our results underscore a detrimental role of MPO activity to post-ischemia neurogenesis and that a strategy to inhibit MPO activity can increase cell proliferation and improve neurogenesis after ischemic stroke.

Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia

Whatever the hell postconditioning is.
Earlier research explanation of it here:

Ischemic postconditioning as a novel avenue to protect against brain injury after stroke

The new one here:

Effects of Postconditioning on Neurogenesis and Angiogenesis During the Recovery Phase After Focal Cerebral Ischemia

1. Elga Esposito, PhD,
2. Kazuhide Hayakawa, PhD,
3. Takakuni Maki, MD, PhD,
4. Ken Arai, PhD and
5. Eng H. Lo, PhD

+ Author Affiliations

1. From the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.

1. Correspondence to Eng H. Lo, PhD, or Elga Esposito, PhD, Massachusetts General Hospital, E Bldg 149, 13th St, Charlestown, MA 02129. E-mail lo@helix.mgh.harvard.edu or eesposito@partners.org

Abstract

Background and Purpose—Postconditioning may be a clinically feasible way to protect the brain after a stroke. However, its effects during the recovery phase post stroke remain to be fully elucidated. Here, we examine the hypothesis that ischemic postconditioning amplifies neurogenesis and angiogenesis during stroke recovery.

Methods—Male Sprague–Dawley rats were subjected to 100-minute transient middle cerebral artery occlusion (MCAO) or postconditioning (100-minute middle cerebral artery occlusion plus 10-minute reperfusion plus 10-minute reocclusion). After 2 weeks, infarct volumes, behavioral outcomes, and immunohistochemical markers of neurogenesis and angiogenesis were quantified.

Results—Postconditioning significantly reduced infarction and improved neurological outcomes. Concomitantly, brains subjected to postconditioning showed an increase in doublecortin/BrdU and collagen-IV/Ki67-positive cells.

Conclusions—These results suggest that therapeutic effects of postconditioning may involve the promotion of neurogenesis and angiogenic remodeling during the recovery phase after focal cerebral ischemia.

Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice

So maybe TCM will finally prove itself.
http://www.sciencedirect.com/science/article/pii/S0306452215005412

• F. Li^a,
• H.X. Dong^{a, b},
• Q.H. Gong^a,
• Q. Wu^a,
• F. Jin^a,
• J.S. Shi^{a, ,}

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doi:10.1016/j.neuroscience.2015.06.010

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Highlights

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Icariin improved the spatial working memory of Tg2576 mice.

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Icariin reduced the level of insoluble Aβ_1-40 and Aβ_1-42 and the protein expression of APP in Tg2576 mice cortex.

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Icariin increased the adult neurogenesis in the dentate gyrus of hippocampus of Tg2576 mice.

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Abstract

Icariin is a major component derived from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from the neurotoxicity and ischemia-conditions. In this study, we investigated the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer’s disease (AD). Tg2576 mice and wild type littermates (WT) were randomly assigned to three groups: Tg2576, Tg2576+icariin and WT groups. At 9 months old, all mice were treated with icariin (60 mg/kg/d) or distilled water for 3 months. The results showed that administration with icariin for 3 months improved the spatial working memory of Tg2576 mice as examined in Y-maze task. Furthermore, icariin treatment reduced the level of insoluble Aβ_1-40 (69%) and Aβ_1-42 (50%) in the cortex and hippocampus as determined by ELISA. Western blot analysis indicated the down-regulation of the APP expression, and double staining showed the elevation of BrdU/NeuN double-positive cells in the dentate gyrus region of hippocampus compared with Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain and increased the neurogenesis in the hippocampus of Tg2576 mice. Taken together, these results suggest that icariin could be a potential drug candidate for AD treatment.

Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway

This seems like good  research to follow up with human trials, interventions from day 1 to day 6, so no real need for speed. But since we have no one in charge of any stroke strategy this will fall thru the cracks like most of the research I write about. Complete failure by the existing stroke associations.
http://www.nature.com/aps/journal/vaop/ncurrent/full/aps2014156a.html

Xin-yu Liu, Xin-yu Zhou, Jin-cai Hou, Hua Zhu, Zhong Wang, Jian-xun Liu and Yong-qiu Zheng

Abstract

Aim:

To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI).

Methods:

Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg⁻¹·d⁻¹, ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg⁻¹·d⁻¹, ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting.

Results:

Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg⁻¹·d⁻¹) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 μmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002.

Conclusion:

Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.

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Enhancement of hippocampal neurogenesis by lithium

This is in rodents so don't start bugging your doctor that you need lithium. Unless maybe you are already taking this for bipolar or Schizophrenia.
http://www.ncbi.nlm.nih.gov/pubmed/10987856 

Chen G¹, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji HK.

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Abstract

Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that approximately 65% of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.

Radiolabeled neurogenesis marker imaging: a revolution in the neurological diseases management?

If this works and you can see where neurogenesis takes place then maybe our neurologists can create some repeatable stroke protocols for that. But I doubt our neurologists can do anything outside of reading textbooks.  A neurologist could prove me wrong but they won't.
http://www.sciencedirect.com/science/article/pii/S0306987713005707

• Reza Nemati^a,
• Somayeh Mehdizadeh^a,
• Iraj Nabipour^b,
• Hooman Salimipour^b,
• Darioush Iranpour^b,
• Majid Assadi^{b, ,}

• ^a Department of Neurology, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
• ^b The Persian Gulf Nuclear Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran

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Abstract

A reduced rate of neurogenesis occurs in the adult brain of patients with neurological diseases, with the rate of new neuron proliferation not sufficient to replace neuron loss. Neurogenesis can be induced by several factors, including basic fibroblast growth factor, epidermal growth factor, and brain-derived neurotrophic factor.

Neurogenesis determination is a valuable parameter for determining disease progression and monitoring various treatments. Currently, neurogenesis detection is possible by invasive methods, such as bromodeoxyuridine (BrdU) cell labeling and immunohistological analysis of immature neuron markers. However, these are not compatible with alive model examination. Neurogenesis detection by noninvasive methods, such as radiolabeling of specific antibodies and scintigraphy imaging, could shed light on immature neuronal markers.

We propose that brain scintigraphy after radiolabeling of a specific antibody of an immature neuronal marker is a useful new modality for neurogenesis detection and that it would aid the management of neurological diseases.