Curcumin alleviates neuroinflammation, enhances hippocampal neurogenesis, and improves spatial memory after traumatic brain injury

WHOM THE HELL do we go to to get this tested for stroke and in humans? I want SPECIFIC NAMES that will take responsibility for followthru.

Curcumin alleviates neuroinflammation, enhances hippocampal neurogenesis, and improves spatial memory after traumatic brain injury

Author links open overlay panelGuangchiSun^a1PengzhanZhao^a1LiangFan^bZhongyuanBao^aYimingTu^aChongLi^aHongluChao^aXiupengXu^aJingJi^a

https://doi.org/10.1016/j.brainresbull.2020.05.009Get rights and content

Highlights

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Curcumin rescued spatial memory after TBI in rats.

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Curcumin decreased TBI-induced chronic neuroinflammation.

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Curcumin increased hippocampal neurogenesis after TBI.

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Curcumin may regulate these changes via the BNDF/Trkb/PI3K/AKT pathway.

Abstract

Cognitive decline is one of the most obvious symptoms of traumatic brain injury (TBI). Previous studies have demonstrated that cognitive decline is related to substantially increased neuroinflammation and decreased neurogenesis in the hippocampus in a rat model of TBI. Using this model, we explored the role of curcumin (Cur) in ameliorating TBI-impaired spatial memory because Cur has been shown to exhibit anti-chronic-neuroinflammatory, neurogenesis-promoting, and memory-improving properties.

Animals received daily Cur or vehicle treatment for 28 days after TBI and also received 50-bromodeoxyuridine(BrdU) for the first 7 days of the treatment for assaying neurogenesis. An optimal Cur dose of 30 mg/kg, selected from a range of 10–50 mg/kg, was used for the present study. Neuroinflammation was evaluated by astrocyte hypertrophy, activated microglia, and inflammatory factors in the hippocampus. Behavioral water-maze studies were conducted for 5 days, starting at 35-day post-TBI. The tropomyosin receptor kinase B (Trkb) inhibitor, ANA-12, was used to test the role of the brain-derived neurotrophic factor (BDNF)/ TrkB/Phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in regulating inflammation and neurogenesis in the hippocampus.

Treatment with Cur ameliorated the spatial memory of TBI rats, reduced TBI-induced chronic inflammation, typified by diminished astrocyte hypertrophy, reduction in activated microglia, declined inflammatory factors, and increased neurogenesis in the hippocampus. We also found that BDNF/Trkb/PI3K/Akt signaling was involved in the effects of Cur in TBI rats.

Thus, Cur treatment can ameliorate the spatial memory in a murine model of TBI, which may be attributable to decreased chronic neuroinflammation, increased hippocampal neurogenesis, and/or BDNF/Trkb/PI3K/Akt signaling.

How memory function could be preserved after brain injury

WHOM THE HELL do we go to to get this tested for stroke survivors? It sounds promising for memory problems.  I want a specific name to have responsibility to drive this thru to completion.  That is just basic Business 101, which obviously the stroke medical world is oblivious to. But they are at Ph.D levels in incompetence. 

2 years ago this came out. Did your fucking failure of a hospital do ONE DAMN THING WITH IT?

It was in rats so your doctor and stroke hospital were responsible to followup with researchers to get this tested in humans. Failure to do so should be grounds for firing.  I hate keeping incompetent people in their jobs.

Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury Possibly via High Mobility Group Box 1/Toll-Like Receptor 4/NFκB Pathway May 2018

 

How memory function could be preserved after brain injury

A study examining the effect of the immune receptor known as Toll-like Receptor 4, or , on how memory functions in both the normal and injured brain has found vastly different cellular pathways contribute to the receptor's effects on excitability in the uninjured and injured brain.

Further, the researchers found novel mechanisms for how TLR4 regulates memory function in the normal, uninjured brain.
The study, performed on rats and published in Brain, Behavior, and Immunity, has the potential to lead to treatments aimed at limiting memory deficits after brain injury.
"Memory deficits are a major long term adverse consequence of brain injury and the ability of a drug treatment given a day after injury to improve memory function is of significant clinical interest," said Viji Santhakumar, an associate professor of molecular, cell and systems biology at the University of California, Riverside, who led the study. "Resatorvid, a drug approved for clinical trials in other diseases, effectively blocked TLR4 and improved post-injury memory deficits in our study."

The brain has neurons and non-neuronal cells called glia. In the normal brain, the activity of neurons is suppressed by TLR4; in the injured brain, TLR4 increases neuronal activity. Specifically, following brain injury, TLR4 increases excitability in the dentate gyrus, a circuit involved in memory processing in the hippocampus, the brain structure that plays a major role in learning and memory.

The UC Riverside-led study found only neurons are involved in TLR4-mediated increase in excitability in the injured brain. In contrast, glial cells are necessary for TLR4-mediated reduction of excitability in the normal brain.
"We found suppressing TLR4 signaling a day after concussive brain injury, common to sports and traffic accidents, reduces excitability and improves working memory performance a week to a month later," she said. "Our data show the processes underlying the damaging effects of brain injury can be selectively manipulated for therapy and can preserve memory function after the injury."
How exactly TLR4 affects memory function in the normal and injured brain is not clear.
"While the actual mechanisms are not known, the speculation is that TLR4 regulates memory function by suppressing neuronal activity in the normal brain, thereby improving signal-to-noise ratio," Santhakumar said. "After injury, the effect of TLR4 flips to enhancing neuronal activity and promoting excitability, which increases noisy and non-specific neuronal firing and degrades signal-to-noise. It is possible that after injury TLR4 impairs cellular processes involved in memory formation, which my lab is currently investigating. The bottom line is that inhibiting TLR4 signaling in the injured brain leads to improvements in long-term working memory deficits for weeks to a month."

Santhakumar was intrigued by a common immune signaling molecule, TNFα, which contributes to both TLR4-dependent reduction in excitability in normal, uninjured brains, and TLR4-mediated increase in excitability after concussive brain injury. In the normal brain, glial cells are involved; in the injured brain, neurons are involved.

"Our study has identified a novel role for neuronal TNFα in regulating excitability," she said. "We were surprised that glial versus neuronal signaling mediated by the same signaling molecule, TNFα, has different effect on neuronal excitability."
Next, Santhakumar and her team plan to determine how TLR4 signaling through glial mediators suppresses network excitability and facilitates memory performance in the normal brain. The researchers also plan to explore how neuronal TLR4 signaling after injury can be selectively manipulated.
"We are interested in determining if blocking TLR4 signaling after injury prevents network reorganization and abnormal changes in rhythmic or oscillatory brain activity that is crucial to memory processing," she said.
Santhakumar was joined in the study by Akshata A. Korgaonkar, the first author of the research paper who is a postdoctoral researcher at the Washington University School of Medicine in St. Louis; Susan Nguyen, Dipikar Sekhar, and Deepak Subramanian of UCR; and Ying Li, Jenieve Guevarra, and Kevin C. H. Pang of the Rutgers New Jersey Medical School, where Santhakumar, an expert in epilepsy and traumatic brain injury, worked before she joined the UCR faculty in 2018.

The study was supported by the National Institutes of Health; Citizens United for Research in Epilepsy; and the state of New Jersey.

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Story Source:
Materials provided by University of California - Riverside. Original written by Iqbal Pittalwala. Note: Content may be edited for style and length.

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Journal Reference:

1. Akshata A. Korgaonkar, Susan Nguyen, Ying Li, Dipika Sekhar, Deepak Subramanian, Jenieve Guevarra, Kevin C.H. Pang, Vijayalakshmi Santhakumar. Distinct cellular mediators drive the Janus faces of toll-like receptor 4 regulation of network excitability which impacts working memory performance after brain injury. Brain, Behavior, and Immunity, 2020; DOI: 10.1016/j.bbi.2020.03.035

Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis

I would argue that the neuronal cascade of death is preventable. Thus 10 million yearly stroke survivors  are harmed by this. The status quo has nothing to prevent that harm but LEADERS change the status quo. WHOM THE HELL ARE OUR STROKE LEADERS?

Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis

BMJ 2019; 366 doi: https://doi.org/10.1136/bmj.l4185 (Published 17 July 2019) Cite this as: BMJ 2019;366:l4185

Linked editorial

Preventable harm: getting the measure right

• Article
• Related content
• Metrics
• Responses
• Peer review

1. Maria Panagioti, senior lecturer1,  
2. Kanza Khan, PhD candidate1,  
3. Richard N Keers, lecturer2,  
4. Aseel Abuzour, postdoctoral research associate2,  
5. Denham Phipps, lecturer2,  
6. Evangelos Kontopantelis, professor1,  
7. Peter Bower, professor1,  
8. Stephen Campbell, chair1,  
9. Razaan Haneef, foundation year 2 doctor3,  
10. Anthony J Avery, dean4,  
11. Darren M Ashcroft, professor1

Author affiliations

1. Correspondence to: M Panagioti maria.panagioti@manchester.ac.uk

• Accepted 30 May 2019

Abstract

Objective To systematically quantify the prevalence, severity, and nature of preventable patient harm across a range of medical settings globally.

Design Systematic review and meta-analysis.

Data sources Medline, PubMed, PsycINFO, Cinahl and Embase, WHOLIS, Google Scholar, and SIGLE from January 2000 to January 2019. The reference lists of eligible studies and other relevant systematic reviews were also searched.

Review methods Observational studies reporting preventable patient harm in medical care. The core outcomes were the prevalence, severity, and types of preventable patient harm reported as percentages and their 95% confidence intervals. Data extraction and critical appraisal were undertaken by two reviewers working independently. Random effects meta-analysis was employed followed by univariable and multivariable meta regression. Heterogeneity was quantified by using the I² statistic, and publication bias was evaluated.

Results Of the 7313 records identified, 70 studies involving 337 025 patients were included in the meta-analysis. The pooled prevalence for preventable patient harm was 6% (95% confidence interval 5% to 7%). A pooled proportion of 12% (9% to 15%) of preventable patient harm was severe or led to death. Incidents related to drugs (25%, 95% confidence interval 16% to 34%) and other treatments (24%, 21% to 30%) accounted for the largest proportion of preventable patient harm. Compared with general hospitals (where most evidence originated), preventable patient harm was more prevalent in advanced specialties (intensive care or surgery; regression coefficient b=0.07, 95% confidence interval 0.04 to 0.10).

Conclusions Around one in 20 patients are exposed to preventable harm in medical care. Although a focus on preventable patient harm has been encouraged by the international patient safety policy agenda, there are limited quality improvement practices specifically targeting incidents of preventable patient harm rather than overall patient harm (preventable and non-preventable). Developing and implementing evidence-based mitigation strategies specifically targeting preventable patient harm could lead to major service quality improvements in medical care which could also be more cost effective.

How Coffee May Protect Brain Health: A New Study Suggests The Benefits Aren't Just From Caffeine

But I really need to know if the daily 8-12 cups I drink is enough, this didn't answer that question. So followup will be needed. WHOM DO WE CONTACT TO GET THAT DONE? 

It most certainly will not be our fucking failures of stroke associations.

How Coffee May Protect Brain Health: A New Study Suggests The Benefits Aren't Just From Caffeine

David DiSalvo Contributor

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Coffee has been getting considerable attention for a growing list of health benefits, with brain health high among them. While not without a few downsides, studies have shown impressive upsides of moderate coffee consumption, often linked to its high caffeine content. But a new lab study suggests that when it comes to brain health, coffee offers more than the stimulating effects of our favorite legal drug–in fact, decaf could be just as effective.

The study began with a question: why has previous research found that coffee consumption correlates with lower risk of developing neurodegenerative diseases like Alzheimer’s and Parkinson’s?
“We wanted to investigate why that is—which compounds [in coffee] are involved and how they may impact age-related cognitive decline," said lead study author Dr. Donald Weaver, co-director of the Krembil Brain Institute in Toronto.

To investigate why, the research team evaluated several compounds (including caffeine) released during the roasting process in three types of coffee beans: caffeinated dark roast, caffeinated light roast, and decaffeinated dark roast.
The analysis focused on how the compounds interact with amyloid beta and tau, the toxic proteins linked to the development of Alzheimer’s disease. Results from previous studies suggest that coffee compounds could provide a neuroprotective effect by inhibiting these proteins from forming the terminally disruptive clumps and tangles found in the brains of Alzheimer’s patients.

The researchers gradually zeroed in on one particular set of compounds known as phenylindanes that form during the roasting process and give coffee its paradoxically enjoyable bitterness. More than any other compound of those examined in this study, the research team found that phenylindanes inhibit both amyloid beta and tau under laboratory conditions.
"So phenylindanes are a dual inhibitor…we were not expecting that," said Dr. Weaver.
The researchers added that most likely it’s a combination of compounds that provides the biggest benefits from drinking coffee, but the results indicate that phenylindanes—present in both caffeinated and decaf coffee (slightly more in dark roasts)—could be central to its neuroprotective effects.
Since this was a lab study that examined the interaction of coffee compounds with toxic proteins outside the body, the next step is to find out if the same results turn up in human subjects once ingested. While the results aren't yet conclusive, the research is an important starting point to investigate how these compounds interact with proteins responsible for brain-destroying diseases that affect more people every year. The researchers were careful to note that they aren't suggesting that coffee is a cure for these diseases.
"What this study does is take the epidemiological evidence and try to refine it and to demonstrate that there are indeed components within coffee that are beneficial to warding off cognitive decline," said study co-author Dr. Ross Mancini. "The next step would be to investigate how beneficial these compounds are, and whether they have the ability to enter the bloodstream or cross the blood-brain barrier.”
The study was published in the journal Frontiers in Neuroscience.
You can find David DiSalvo on Twitter, Facebook, Google Plus, and at his website, daviddisalvo.org.

Effects of intra-arterial transplantation of adipose-derived stem cells on the expression of netrin-1 and its receptor DCC in the peri-infarct cortex after experimental stroke

Whom the fuck is going to lead the followup research in humans? NO ONE WILL because everyone is waiting for SOMEONE ELSE TO SOLVE THE PROBLEM?
https://stemcellres.biomedcentral.com/articles/10.1186/s13287-017-0671-6

• Huan Huang,
• Fan Lin,
• Jingjing Jiang,
• Yan Chen,
• Ainong Mei and
• Pengli ZhuEmail authorView ORCID ID profile

Stem Cell Research & Therapy20178:223

https://doi.org/10.1186/s13287-017-0671-6

©  The Author(s). 2017

Received: 22 July 2017

Accepted: 13 September 2017

Published: 10 October 2017

Abstract

Background

Stem cell transplantation has been documented to promote functional recovery in animal models of stroke; however, the underlying mechanisms are not yet fully understood. As netrin-1 and its receptor deleted in colorectal cancer (DCC) are important regulators in neuronal and vascular activities, the present study attempted to explore whether netrin-1 and DCC are involved in the neuroprotection of stem cell-based therapies in a rat ischemic stroke model.

Methods

Adult male Sprague–Dawley rats were subjected to a transient middle cerebral artery occlusion (MCAO) and subsequently received an intra-arterial injection of 2 × 10⁶ PKH26-labeled adipose-derived stem cells (ADSCs) or saline 24 h later. Neurological function was evaluated by behavioral tests before the rats were sacrificed at days 7 and 14 after MCAO. The migration of ADSCs and regeneration of neuronal fibers and blood vessels were determined by immunofluorescence staining. The expression of netrin-1 and DCC was analyzed by Western blot and immunofluorescence staining.

Results

ADSC transplantation significantly improved the neurological recovery at days 7 and 14, and noticeably promoted the regeneration of neuronal fibers and blood vessels in the peri-infarct cortex at day 14. PKH26-labeled ADSCs located mainly in the peri-infarct area at days 7 and 14. In ADSC-treated rats, the expression of netrin-1 and DCC significantly increased in the peri-infarct cortex at days 7 and 14. Immunofluorescence staining showed that netrin-1 was mainly expressed by neuronal perikaryal in the peri-infarct cortex, and DCC was mainly expressed by neuronal fibers and was present around the blood vessels in the peri-infarct cortex.

Conclusions

These findings suggest that ADSC transplantation facilitates the regeneration of neuronal fibers and blood vessels in the peri-infarct cortex and improves neurological functions, which may be attributed, at least in part, to the involvement of upregulated netrin-1 and DCC in the remodeling of neuronal and vascular networks in the peri-infarct cortex.

Dopamine D3 and acetylcholine nicotinic receptor heteromerization in midbrain dopamine neurons: Relevance for neuroplasticity

What does this mean for our needed neuroplasticity? Should we be taking nicotine? Via smoking? Patches? Gum? eCigarettes? Whom the hell is going to answer that simple question? Our fucking failures of stroke associations can once again prove their fucking failures by not even knowing that answering this question could help survivors recover.
http://www.sciencedirect.com/science/article/pii/S0924977X17300482

• Leonardo Bontempi^, ,
• Paola Savoia,
• Federica Bono,
• Chiara Fiorentini,
• Cristina Missale

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http://dx.doi.org/10.1016/j.euroneuro.2017.01.015

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Abstract

Activation of nicotinic acetylcholine receptors (nAChR) promotes the morphological remodeling of cultured dopamine (DA) neurons, an effect requiring functional DA D3 receptors (D3R). The aim of this study was to investigate the mechanisms mediating D3R-nAChR cross-talk in the modulation of DA neuron structural plasticity. By using bioluminescence resonance energy transfer² (BRET²) and proximity ligation assay (PLA), evidence for the existence of D3R-nAChR heteromers has been obtained. In particular, BRET² showed that the D3R directly and specifically interacts with the β2 subunit of the nAChR. The D3R-nAChR complex was also identified in cultured DA neurons and in mouse Substantia Nigra/Ventral Tegmental Area by PLA. Cell permeable interfering peptides, containing highly charged amino acid sequences from the third intracellular loop of D3R (TAT-D3R) or the second intracellular loop of the β2 subunit (TAT-β2), were developed. Both peptides, but not their scrambled counterparts, significantly reduced the BRET² signal generated by D3R-GFP² and β2-Rluc. Similarly, the PLA signal was undetectable in DA neurons exposed to the interfering peptides. Moreover, interfering peptides abolished the neurotrophic effects of nicotine on DA neurons. Taken together these data first demonstrate that a D3R-nAChR heteromer is present in DA neurons and represents the functional unit mediating the neurotrophic effects of nicotine.

Keywords

• Nicotine;
• Heteromerization;
• Plasticity;
• Dopamine;
• D3 Receptor;
• Nicotinic receptor

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Corresponding author.

© 2017 Elsevier B.V. and ECNP. All rights reserved.

Walking,walking, walking

On the last day in France with only 12,000 steps and walking uphill with a toe crest under my left toes. I  still managed to have enough spasticity  in my toes to be walking on the tips of my toes. What the hell is it going to take to get rid of that fucking toe spasticity?
My God in the last 2.9 years I've  walked 4,036,206 steps.
What the hell is it going to take to release that spasticity?

Who in the world knows what to do to relieve spasticity?

Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling

Whom the hell is going to follow up this research and create a stroke protocol? No one will because we having NO fucking strategy and NO fucking stroke leadership. You're screwed.
http://onlinelibrary.wiley.com/doi/10.1111/jpi.12300/abstract

1. Yushu Dong^1,†,
2. Chongxi Fan^2,3,†,
3. Wei Hu^2,†,
4. Shuai Jiang⁴,
5. Zhiqiang Ma³,
6. Xiaolong Yan³,
7. Chao Deng⁵,
8. Shouyin Di³,
9. Zhenlong Xin²,
10. Guiling Wu²,
11. Yang Yang^2,*,
12. Russel J. Reiter^6,* and
13. Guobiao Liang^1,*

DOI: 10.1111/jpi.12300

This article is protected by copyright. All rights reserved.

Issue

Journal of Pineal Research

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

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Author InformationPublication History

1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jpi.12300

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Keywords:

• Melatonin;
• Subarachnoid hemorrhage;
• Early brain injury;
• Inflammasome;
• Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3

Abstract

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. The current study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 h after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

This article is protected by copyright. All rights reserved.

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