Integrin β1 and the Repair after Nervous System Injury

You tell us about the central role of integrin β1 but nothing on how it can be used to recover. Useless.

Integrin β1 and the Repair after Nervous System Injury

Eur Neurol

https://doi.org/10.1159/000526690

• Abstract
• FullText
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• Extras : 2

Abstract

Background: 

Integrin β1, as a member of the adhesion molecule family, is widely distributed in many kinds of cells and participates in multiple biological functions of the nervous system, including cytoskeleton reorganization, axon growth, and inflammatory injury.  

Summary: 

After nervous system injury, integrin β1 expressed by microglia is mainly involved in promoting inflammatory damage; integrin β1 expressed by astrocytes plays an important role in axon regeneration; integrin β1 expressed by endothelial cells mainly participates in vascular remodeling. We concluded that the function of integrin β1 depends on the location of the receptor cells. The mechanism of integrin β1, which is involved in the inflammatory response of immune regulatory cells and affects the axonal regeneration of neuronal cells, is the key to explore the repair after nervous system injury. The development of drugs targeting integrin β1 is expected to bring a breakthrough in the treatment of nervous system injury.  

Key Messages: 

This paper expounds the important role of microglia in neurons of the nervous system and emphasizes the central role of integrin β1 in regulating non-neuronal cells after nervous system damage.

© 2022 The Author(s). Published by S. Karger AG, Basel

Yan L. · Cui Z. Author affiliations Corresponding Author Keywords: IntegrinAxon regenerationNervous system injuryMicrogliaAstrocytes

 

Review of the Elemental Status in Blood Serum in Patients with Ischemic Stroke

 No clue what this research was for.

Review of the Elemental Status in Blood Serum in Patients with Ischemic Stroke

View article (Download PDF file)

¹ Aksana N. Mazilina, ^1,3 Anatoliy V. Skalny, ^2,4 Anatoliy D. Fesyun, ^2,3 Maxim Yu. Yakovlev, ³ Sergey A. Savko, ³ Evegeniya D. Namiot

¹ Peoples’ Friendship University of Russia, Moscow, Russian Federation
² National Medical Research Center of Rehabilitation and Balneology, Moscow, Russian Federation
³ I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
⁴ Moscow State University of Food Production, Moscow, Russian Federation

Abstract:

The study of the elemental status in the modern paradigm of medical diagnostics occupies an increasingly large niche due to the possible use of trace elements as possible predictors of cerebrovascular pathologies. Moreover, the great importance of the elemental component in the main enzymatic systems of metabolism allows us to consider them also as a therapeutic target. There are many mechanisms in the pathophysiology of stroke development, each of which, in one way or another, is mediated through the interaction of regulatory proteins with trace elements as cofactors. Therefore, it is necessary to pay close attention to elemental homeostasis in the focus of ischemic pathologies.

Aim. 

Systematization of the known pathogenetic effects of the most metabolic homeostasis important elements on the course of stroke,both contributing factors to earlier rehabilitation and minimal neurological defi cit after the ischemic event itself, and factors aggravating the recovery process and leading to serious neurological consequences. This pursues not only a prognostic goal to determine the severity of ischemia or to identify risk groups with certain shifts in elemental constants, but also the therapeutic one — to replace the falling functions of the dropping metabolic agents, as happens with the elements involved in antioxidant systems. It is also necessary to develop a methodology for stopping the excess of nerve cells mediating excitotoxicity with calcium ions, which closes the vicious circle of vascular necrosis with additional destruction of the nervous tissue.

Conclusion. 

The conclusions that we can summarize quite convincingly indicate a significant contribution of the elemental status to the pathogenesis of ischemic stroke. Dysregulation of the elemental component can force the damaging effect of ischemia on brain cells. At the same time, many elements show a surplus during an ischemic event: Li, I, Mn, Zn, As, Se, Pb, Sr, Ni, however, not all of the presented elements negatively affect the course of stroke, since an increase in the level of some metals may be compensatory in nature,and for their further applicability as diagnostic and therapeutic agents, similar analytics are required.

Keywords: stroke, trace elements, elementary homeostasis, ischemia

For citation: Mazilina A.N., Skalny A.V., Fesyun A.D., Yakovlev M.Yu., Savko S.A., Namiot D.E. Review of the Elemental Status in Blood Serum in Patients with Ischemic Stroke. Bulletin of Rehabilitation Medicine. 2022; 21 (1):104-113. https://doi.org/10.38025/2078-1962-2022-21-1-104-113

Neuroprotective Effect of Angiopoietin2 Is Associated with Angiogenesis in Mouse Brain Following Ischemic Stroke

Any research that has neuroprotection working in animals should immediately have research conducted in humans. But it won't since we have NO STROKE LEADERSHIP OR STRATEGY!  It's amazingly obvious to everyone but the stroke medical world.

 Neuroprotective Effect of Angiopoietin2 Is Associated withAngiogenesis in Mouse Brain Following Ischemic Stroke

Citation: Lv, L.-L.; Du, Y.-T.; Chen, X.;
Lei, Y.; Sun, F.-Y. Neuroprotective
Effect of Angiopoietin2 Is Associatedwith Angiogenesis in Mouse BrainFollowing Ischemic Stroke. Brain Sci.2022, 12, 1428. https://doi.org/10.3390/brainsci12111428Academic Editors: Kenneth Fong andKunwei WuReceived: 20 September 2022Accepted: 20 October 2022Published: 24 October 2022Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Copyright: © 2022 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).brainsciencesLing-Ling Lv 1,2,†, Yi-Ting Du 1,2,†, Xiao Chen1,2, Yu Lei 1,2 and Feng-Yan Sun 1,2,*1 Department of Neurobiology and State Key Laboratory of Medical Neurobiology, School of Basic MedicalSciences, Shanghai Medical College, Fudan University, Shanghai 200032, China2Institute for Basic Research on Aging and Medicine of School of Basic Medical Sciences and National ClinicalResearch Center for Aging and Medicine, Huashan Hospital, Hanghai Medical College, Fudan University,Shanghai 200032, China* Correspondence: fysun@shmu.edu.cn† These authors contributed equally to this work.

Abstract: 

 Angiogenic factors play an important role in protecting, repairing, and reconstructingvessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34+vascular length andarea. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury,and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.

The regulatory roles of circular RNAs via autophagy in ischemic stroke

 You're trying to describe something but I couldn't figure out how this will help survivors recover

The regulatory roles of circular RNAs via autophagy in ischemic stroke

Xiaoqin Li^1†, Lingfei Li^2†, Xiaoli Si^3†, Zheng Zhang¹, Zhumei Ni⁴, Yongji Zhou², Keqin Liu², Wenqing Xia², Yuyao Zhang¹, Xin Gu¹, Jinyu Huang⁵, Congguo Yin^1,2*, Anwen Shao^6,7* and Lin Jiang^1,2*

• ¹The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
• ²Department of Neurology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
• ³Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
• ⁴Department of Emergency, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
• ⁵Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China
• ⁶Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
• ⁷Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Disease, Hangzhou, China

Ischemic stroke (IS) is a severe disease with a high disability, recurrence, and mortality rates. Autophagy, a highly conserved process that degrades damaged or aging organelles and excess cellular components to maintain homeostasis, is activated during IS. It influences the blood–brain barrier integrity and regulates apoptosis. Circular RNAs (circRNAs) are novel non-coding RNAs involved in IS-induced autophagy and participate in various pathological processes following IS. In addition, they play a role in autophagy regulation. This review summarizes current evidence on the roles of autophagy and circRNA in IS and the potential mechanisms by which circRNAs regulate autophagy to influence IS injury. This review serves as a basis for the clinical application of circRNAs as novel biomarkers and therapeutic targets in the future.

Introduction

Stroke is a leading cause of death and disability worldwide (1) and can be classified as ischemic stroke (IS) or hemorrhagic stroke (2). The major type is IS, accounting for 71% of cases (2). During IS, ischemia and hypoxia cause neuronal and glial anoxic depolarization (3), which increases extracellular levels of glutamate, leading to excess calcium influx and release of calcium from intracellular stores (4). Increased intracellular calcium contributes to neuronal nitric oxide synthase activation with consequent free radical production and the initiation of cell death processes, including apoptosis, necrosis, necroptosis, and autophagy. Current effective treatments for IS include restoration of blood flow through intravenous thrombolysis and neuroscientific intravascular recanalization, both of which reduce disability (2); however, these treatment methods are still limited owing to the limited time window, numerous contraindications (5), and high risk of hemorrhagic complications (6).

Autophagy is activated to varying degrees after IS to restore neuronal homeostasis (2, 7). Autophagy functions in IS by sequestering damaged or aged organelles, superfluous proteins, and cellular components into double membrane-bound vesicles, delivering cytoplasmic cargo to the lysosome, to which it subsequently fuses to form an autolysosome, finally leading to digestion and recycling (8). Autophagy presents a dual effect following ischemic insult. Mild to moderate induction of autophagy can be protective in IS (9), whereas an excessive increase in autophagic activity might be harmful owing to the cytosolic accumulation of autophagosomes and enhanced degradation of essential cellular components (10). Autophagy is divided into two groups according to the role it plays in IS: maladaptive and adaptive autophagy (11).

Circular RNAs are a novel type of non-coding RNAs (12) with a stable and evolutionally conserved covalent loop structure (13). Previous studies have demonstrated that circRNAs are often specifically expressed in tissue and developmental stages (14) and are highly expressed in the mammalian brain (15). CircRNAs are upregulated during neuronal differentiation and are highly enriched in synapses (16). The role of circRNAs has been identified in several human diseases, including neurological disorders, cardiovascular diseases, diabetes mellitus, chronic inflammatory diseases, and cancer (17–21). Interestingly, circRNAs function in ischemic brain injury (22–25); therefore, they are potential biomarkers for IS and may serve as new therapeutic targets.

More at link.

Targeting neuroplasticity to improve motor recovery after stroke: an artificial neural network model

Great word salad but I see nothing that is going to get survivors recovered.

 Targeting neuroplasticity to improve motor recovery after stroke: an artificial neural network model

Sumner L. Norman1,2,*, Jonathan R. Wolpaw3, and David J. Reinkensmeyer2
1Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
2Mechanical and Aerospace Engineering, University of California: Irvine, Irvine, CA, USA
3National Center for Adaptive Neurotechnologies, Stratton VA Medical Center and State University of
New York, Albany, NY, USA
*Correspondence to: Sumner L. Norman, Ph.D., 1200 E California Blvd, MC 216-76, Pasadena, CA 91125
USA, sumnern@caltech.edu

Abstract

After a neurological injury, people develop abnormal patterns of neural activity that limit motor recovery. Traditional rehabilitation, which concentrates on practicing impaired skills, is seldom fully effective. New targeted neuroplasticity protocols interact with the central nervous system (CNS) to induce beneficial plasticity in key sites and thereby enable wider beneficial plasticity. They can complement traditional therapy and enhance recovery. However, their development and validation is difficult because many different targeted neuroplasticity protocols are conceivable, and evaluating even one of them is lengthy, laborious, and expensive. Computational models can address this problem by triaging numerous candidate protocols rapidly and effectively. Animal and human empirical testing can then concentrate on the most promising ones. Here we simulate a neural network of corticospinal neurons that control motoneurons eliciting unilateral finger extension. We use this network to (1) study the mechanisms and patterns of cortical reorganization after a stroke, and (2) identify and parameterize a targeted neuroplasticity protocol that improves recovery of extension torque. After a simulated stroke, standard training produced abnormal bilateral cortical activation and suboptimal torque recovery. To enhance recovery, we interdigitated standard training with trials in which the network was given feedback only from a targeted population of sub-optimized neurons. Targeting neurons in secondary motor areas on ~20% of the total trials restored lateralized cortical activation and improved recovery of extension torque. The results illuminate mechanisms underlying suboptimal cortical activity post-stroke; they enable
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https://mc.manuscriptcentral.com/braincom

An Intelligent Motor Assessment Method Utilizing a Bi-lateral Virtual-Reality Task for Stroke Rehabilitation on Upper Extremity

Well, assessment crapola again, NOT any useful recovery protocols.

 An Intelligent Motor Assessment Method Utilizing a Bi-lateral Virtual-Reality Task for Stroke Rehabilitation on Upper Extremity

CHIA-RU CHUNG1, MU-CHUN SU1, SI-HUEI LEE2,3, ERIC HSIAO-KUANG WU1, LI-HSIEN
TANG1, AND SHIH-CHING YEH1
1Department of Computer Science and Information Engineering, National Central University, Taoyuan 320,
Taiwan
2Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei 112, Taiwan
3National Yang-Ming University, Taipei 112, Taiwan
CORRESPONDING AUTHOR: Eric Hsiao-Kuang Wu (hsiao@csie.ncu.edu.tw)

Abstract

 Virtual reality(VR) has been widely adopted by therapists to provide rich motor training tasks.Time series data of motion trajectory accompanied with the interaction of VR system may contain important clues regard to the assessment of motor function, however, clinical evaluation scales as Fugl-Meyer Assessment (FMA), Wolf Motor Test(WMFT), Test D'évaluation Membres Supérieurs Des Personnes  gées(TEMPA) are highly depended clinic. Further, there is not an assessment method that simultaneously consider motion trajectory and evaluation The objective of this study is establish an evidence based assessment model by machine learning method integrated motion trajectory task clinical evaluation scales. study, VR system upper limb motor training was proposed for stroke rehabilitation. Clinical trials with 20 stroke patients were performed. A variety of motor indicators that derived via motion trajectory were proposed. The correlations between motor indicators and clinical evaluation scales were examined. Further, motor indicators were integrated with evaluation scales develop machine learning based model that represents evidence-based motor assessment approach. Clinical evaluation scales, FMA, TEMPA and WMFT, were significantly progressed. A few motor indicators were found significantly correlated with clinical evaluation scales. The accuracy of machine learning based assessment model was upto 86%. The proposed VR system is validated to be effective in motor rehabilitation. Motor indicators derived from motor trajectory were with potential for clinical motor assessment. Machine learning could be a promising tool to perform automatic assessment. 

Index Terms

—Stroke rehabilitation, Motor training, Virtual reality, Machine learning.
Clinical and Translational Impact Statement—A VR task for motor rehabilitation was exanimated via clinical trials. Integrating motor indices with clinical assessment, a machine-learning model with accuracy of 86% was developed to evaluate motor function

High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

What will your doctor takeaway from this and all this other research on what the proper protocol is for cerebral blood flow and oxygenation? If your doctor has DONE NOTHING  on cerebral blood flow and oxygenation then you don't have a functioning stroke doctor or hospital.   

• cerebral blood flow (27 posts to July 2016)

• oxygenation (5 posts to March 2013)

 

High arterial oxygen levels and supplemental oxygen administration in traumatic brain injury: insights from CENTER-TBI and OzENTER-TBI

• Emanuele Rezoagli,
• Matteo Petrosino,
• Paola Rebora,
• David K. Menon,
• Stefania Mondello,
• D. James Cooper,
• Andrew I. R. Maas,
• Eveline J. A. Wiegers,
• Stefania Galimberti,
• Giuseppe Citerio on behalf of
• CENTER-TBI, OzENTER-TBI Participants and Investigators

Intensive Care Medicine (2022)Cite this article

• 1756 Accesses

• 49 Altmetric

• Metrics details

Abstract

Purpose

The effect of high arterial oxygen levels and supplemental oxygen administration on outcomes in traumatic brain injury (TBI) is debated, and data from large cohorts of TBI patients are limited. We investigated whether exposure to high blood oxygen levels and high oxygen supplementation is independently associated with outcomes in TBI patients admitted to the intensive care unit (ICU) and undergoing mechanical ventilation.

Methods

This is a secondary analysis of two multicenter, prospective, observational, cohort studies performed in Europe and Australia. In TBI patients admitted to ICU, we describe the arterial partial pressure of oxygen (PaO₂) and the oxygen inspired fraction (FiO₂). We explored the association between high PaO₂ and FiO₂ levels within the first week with clinical outcomes. Furthermore, in the CENTER-TBI cohort, we investigate whether PaO₂ and FiO₂ levels may have differential relationships with outcome in the presence of varying levels of brain injury severity (as quantified by levels of glial fibrillary acidic protein (GFAP) in blood samples obtained within 24 h of injury).

Results

The analysis included 1084 patients (11,577 measurements) in the CENTER-TBI cohort, of whom 55% had an unfavorable outcome, and 26% died at a 6-month follow-up. Median PaO₂ ranged from 93 to 166 mmHg. Exposure to higher PaO₂ and FiO₂ in the first seven days after ICU admission was independently associated with a higher mortality rate. A trend of a higher mortality rate was partially confirmed in the OzENTER-TBI cohort (n = 159). GFAP was independently associated with mortality and functional neurologic outcome at follow-up, but it did not modulate the outcome impact of high PaO₂ levels, which remained independently associated with 6-month mortality.

Conclusions

In two large prospective multicenter cohorts of critically ill patients with TBI, levels of PaO₂ and FiO₂ varied widely across centers during the first seven days after ICU admission. Exposure to high arterial blood oxygen or high supplemental oxygen was independently associated with 6-month mortality in the CENTER-TBI cohort, and the severity of brain injury did not modulate this relationship. Due to the limited sample size, the findings were not wholly validated in the external OzENTER-TBI cohort. We cannot exclude the possibility that the worse outcomes associated with higher PaO₂ were due to use of higher FiO₂ in patients with more severe injury or physiological compromise. Further, these findings may not apply to patients in whom FiO₂ and PaO₂ are titrated to brain tissue oxygen monitoring (PbtO₂) levels. However, at minimum, these findings support the need for caution with oxygen therapy in TBI, particularly since titration of supplemental oxygen is immediately applicable at the bedside.

Take-home message

In two large prospective multicenter cohorts of traumatic brain injured patients, arterial and supplemental oxygen levels varied widely across centers during the first seven days after admission to the intensive care unit.

Exposure to high arterial blood oxygen or high supplemental oxygen—a therapeutic gas immediately titratable at the bedside—was independently associated with 6-month mortality, regardless of brain injury severity.

Introduction

In patients with traumatic brain injury (TBI), hypoxemia is a major predictor of hospital and 6-month mortality [1]. Oxygen supplementation aims to reverse tissue hypoxia and, thus, improve cell viability, organ function, and survival in critically ill patients [2]. However, this may lead to administering more oxygen than needed to patients admitted to the intensive care unit (ICU) [3].

While hyperbaric oxygen is known to be neurotoxic [4], it is not clear whether high normobaric oxygen levels may play a detrimental role in the brain [5]. Hyperoxia, i.e., high inspiratory oxygen fraction, may be associated with excitotoxicity in severe TBI [6]. Furthermore, hyperoxemia, i.e., high blood oxygen partial pressure levels, may potentially worsen organ injury and impact the case fatality rate of critically ill patients with TBI [7, 8]. Therefore, not only too low but even extreme hyperoxemia might cause injury in TBI patients, as David et al. showed [9]. Data on more than 36,000 mixed ICU patients mechanically ventilated with early arterial partial pressure of oxygen (PaO₂) suggested an independent U-shape association with hospital mortality [10]. A recent metanalysis of 32 studies in acute brain-damaged patients highlighted that hyperoxemia, differently defined across studies, was associated with an increased risk of poor neurological outcomes [11]. Patients with a poor neurological outcome also had a significantly higher maximum PaO₂ and mean PaO₂. These associations were present, especially in patients with subarachnoid hemorrhage and ischemic stroke, but not in traumatic brain injured.

Currently, there is no evidence to support the role of hyperoxemia or hyperoxia in a large real-world dataset of critically ill patients admitted to ICU with severe TBI [12,13,14].

Therefore, we described variability across centers in the blood oxygen levels (i.e., PaO₂) and oxygen supplementation distributions (i.e., inspiratory oxygen fraction, FiO₂) and investigated whether high PaO₂ and FiO₂ levels are associated with worse 6-month outcomes. We validated our findings in the multicenter Australian OzENTER-TBI database [15]. Finally, we explored whether PaO₂ and FiO₂ levels may contribute differently to outcomes in the presence of increasing levels of glial fibrillary acidic protein (GFAP), a biomarker of brain injury severity.

The aims of this study are to:

1. 1.

   Describe the values and the differences in PaO₂ and FiO₂ in the first week from ICU admission in mechanically ventilated TBI patients across centers in CENTER-TBI;

2. 2.

   assess whether high levels of PaO₂ or FiO₂ are independently associated with 6-month mortality and unfavorable neurologic outcome in CENTER-TBI;

3. 3.

   evaluate whether the impact of high levels of oxygen exposure or high levels of supplemental oxygen on 6-month outcome could be worsened by increasing brain injury severity, as assessed by acute (first 24 h) serum levels of GFAP in the CENTER-TBI cohort.

All these objectives (except the last one) were subsequently validated in an external cohort of patients with traumatic brain injury from OzENTER-TBI. Hypotheses of the current analyses were that exposure to high oxygen and FiO₂ levels in TBI patients mechanically ventilated and admitted to ICU may promote brain injury and have a negative impact on both functional neurological disability and survival.

Love Coffee? Science Says the 1-Week Rule Maximizes Productivity, Focus, and Learning

I'm a steady state coffee drinker  trying to prevent dementia and Parkisons, now doing half decaf, half leaded.

Love Coffee? Science Says the 1-Week Rule Maximizes Productivity, Focus, and Learning

Research shows coffee can help increase energy and focus, but only if you mix in a periodic caffeine reset.

By Jeff Haden, Contributing editor, Inc.@jeff_haden

Photo: Getty Images

It's 7 a.m. and you're struggling to start your workday. Or it's 3 p.m. and your eyes are drooping, and so is your productivity. What do you do? If you're like millions of other people, you reach for a cup of coffee.

And for good reason, since coffee doesn't just kick-start your day by making you feel more alert and awake. (What entrepreneur doesn't need to hit the ground running?) Caffeine also causes your endocrine system to release glutamate, a neurotransmitter that increases your ability to learn and remember. (What entrepreneur doesn't want to keep improving their skills and knowledge?)

In a broader sense, a number of studies recapped by my Inc. colleague Geoffrey James show the health benefits of coffee. Coffee can reduce your risk of cancer up to 20 percent and your risk of Type 2 diabetes and Parkinson's disease by 30 percent.

So, yeah: coffee.

But not too much, or too consistently. Why?

First, a little background. The neurotransmitter adenosine builds up in your system throughout the day; that's one reason you get sleepy. Residual amounts of adenosine still remain in your brain when you wake up; that's one reason you might struggle to get going in the morning. 

That's where caffeine comes in. Caffeine blocks adenosine from binding to receptors in your brain. When adenosine can't bind, you feel, or keep feeling, alert and awake. (Drink enough coffee and you feel really awake.)

But not indefinitely. When your body recognizes that adenosine isn't binding, to paraphrase Jeff Goldblum, life finds a way and responds by creating more receptors. Research shows that within three days of consistent caffeine ingestion, the number of adenosine, nicotinic, and muscarinic (modulation of neuronal excitability) receptors is significantly increased.

More receptors means more coffee is needed to kick-start your day. More coffee is needed to keep you going. If you let the caffeine wear off, the adenosine "crash" is even bigger.

All of which means you start to really need that first cup of coffee. And you start to drink more and more coffee throughout the day, if only to avoid the inevitable caffeine-withdrawal headache.

And at some point, maintaining a constantly caffeinated state becomes your new normal. A 2019 study found that participants in a 20-day study increased their peak cycling power (a fine proxy for feeling alert and energetic) for the first 15 days of ingesting caffeine. The biggest boost came on the first day. After that, adenosine receptors started sprouting like wildflowers. Then the effect steadily diminished, until it reached pre-study levels.

Sound familiar? (Definitely does to me.)

Here's the good news. Research also shows that the changes in adenosine receptor levels typically reverse after a seven-day caffeine break. Think of it as a caffeine reset: By reducing your tolerance, you'll increase the boost you will feel when you start drinking coffee again. 

One way is to take a week off from coffee every month. That's what Ashley Richmond, the founder of Momentum Habits, does. She recommends taking the first week of the month off so it's easy to remember.

If that sounds too harsh, try the slower approach. That's how I overcame a 40-year, 100 or so ounces of diet soda per day habit. (Not coffee, but hey: Caffeine is caffeine.)

Either approach will help you reset your adenosine receptors so you can then maximize the effects of that first -- or afternoon -- cup of coffee.

Without needing to drink more and more to just achieve a steadily diminishing outcome. 

Horrifying – New Study Indicates That Popular Sugar Substitutes Worsen Your Memory

I never really drank any diet drinks at all.

 Horrifying – New Study Indicates That Popular Sugar Substitutes Worsen Your Memory

By University of Southern California October 25, 2022

Consuming low-calorie sweeteners also had an impact on the body’s 

metabolic signaling, which may result in diabetes and other metabolism-related diseases.

Using laboratory models, scientists discovered that ingesting FDA-approved levels of saccharin, ACE-K, and stevia early in life may result in many changes to the body, including brain areas linked to memory and reward-motivated behavior.

Early-life high-sugar diets have been linked to impaired brain function, but what about low-calorie sugar substitutes? According to recent research, they could have a negative impact on the developing gut and brain.

The News

Researchers from the University of Southern California Dornsife College of Letters, Arts, and Sciences report that adolescents who consumed the low-calorie sweeteners saccharin, ACE-K, and stevia showed long-term memory impairments in a study that was recently published in the journal JCI Insight.

• The results are consistent with other studies that demonstrated sustained memory impairment in adolescent rats who consume sugar.
• Consuming low-calorie sweeteners also affected metabolic signaling in the body, which can lead to diabetes and other metabolism-related diseases.
• Rats that ate low-calorie sweeteners as adolescents were less inclined to work for sugar as adults, but they ate more sugar if it was readily accessible, which is another factor that may influence the chance of developing metabolic disease.
  

  Diet soft drinks often use low-calorie sugar substitutes such as stevia and 

  acesulfame potassium, or Ace-K, which might have long-term effects on memory, 

  behavior and metabolic functions.

Why It Matters

There is a broad range of advice on what to eat and when to consume it. According to the researchers, information from studies like these may aid consumers and medical professionals in making better decisions at all stages of life.

“While our findings do not necessarily indicate that someone should not consume low-calorie sweeteners in general, they do highlight that habitual low-calorie sweetener consumption during early life may have unintended, long-lasting impacts,” said Scott Kanoski, associate professor of biological sciences at USC Dornsife.

What It Means for Humans

While most studies of low-calorie sweeteners focus on one substance and use amounts far exceeding the norm, the researchers made sure the study was in line with real-life conditions for people.

• Sweeteners tested include saccharin, acesulfame potassium (ACE-K) and stevia — which are commonly used in sweetened foods.
• The amount of sweetener consumed fell within FDA-approved guidelines for humans.

In Their Words

“Research using rodent models and low-calorie sweeteners has typically involved consumption levels that far exceed the FDA ‘acceptable daily intake’ (ADI) levels and used only a single sweetener. To design our research to be more applicable to humans, we kept consumption levels within the ADI and used multiple low-calorie sweeteners to determine if effects were specific to a given sweetener or general across sweeteners.” — Lindsey Schier, Gabilan Assistant Professor of Biological Sciences at USC Dornsife

The Experiment

To determine the effect of low-calorie sweetener consumption on memory, the researchers used methods that test object recognition and spatial recognition.

Rats were provided water sweetened with either stevia, ACE-K or saccharin or plain water, along with their normal food.
After a month, the rats’ memory was tested using two different methods — one tests if they remember an object they’ve seen before and the other is a maze.
In the end, rats consuming sweetener were less likely to remember an object or the path through the maze than those that drank only plain water.

What Else?

The scientists also found other effects among the rats after they consumed sweeteners.

• They had fewer receptors on their tongues that detect sweet taste.
• The biological mechanism in their intestines that transports glucose into the blood was altered.
• Their brains had changed, specifically in regions associated with memory control and reward-motivated behavior.

What’s Next?

Kanoski and Schier say the findings reveal more questions worth exploring, including:

• How do sweetener substitutes cause a reduction in sweet taste receptors and how does that affect later dietary behavior?
• What does the change in the nutrient transport in the gut mean for health?
• What biological mechanisms link sweetener consumption with the changes to the brain?

The researchers say they intend to explore ways to reverse the long-lasting effects of adolescent low-calorie sweetener consumption and to study how it influences food choices and preferences later in life.

Reference: “Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats” by Linda Tsan, Sandrine Chometton, Anna M.R. Hayes, Molly E. Klug, Yanning Zuo, Shan Sun, Lana Bridi, Rae Lan, Anthony A. Fodor, Emily E. Noble, Xia Yang, Scott E. Kanoski and Lindsey A. Schier, 13 September 2022, JCI Insight.
DOI: 10.1172/jci.insight.157714

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Insitute on Deafness and Other Communication Disorders, and the National Science Foundation.

Dementia: How falls, poorer health may help predict earlier diagnosis up to 9 years

Your doctor better do baseline testing for you post stroke so EXACT PROTOCOLS CAN BE INITIATED TO PREVENT ANY FURTHER DECLINE!

Your risk of dementia, has your doctor told you of this?

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

What is your doctor's EXACT PROTOCOL TO PREVENT DEMENTIA?

Dementia: How falls, poorer health may help predict earlier diagnosis up to 9 years

Diagnosing dementia earlier may help scientists come up with better treatments. Westend61/Getty Images

• More than 55 million people globally have dementia.
• Researchers from the University of Cambridge show it is possible to see signs of dementia as early as nine years before a person receives a diagnosis.
• Scientists also found those who developed Alzheimer’s were more likely to have had a fall and had poorer overall health at baseline.

More than 55 million peopleTrusted Source around the world have dementia — a group of conditions affecting a person’s brain function.

Although there is currently no cure for dementia, the earlier a doctor can diagnoseTrusted Source a person with dementia, the better in terms of symptom management, treatmentTrusted Source, and slowing its progression.

Now, a team of researchers from the University of Cambridge shows it is possible to view dementia signs in people as early as nine years before they receive a diagnosis.

This study was recently published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

What is dementia?

Dementia impacts the brain, making it difficult to remember things, communicate, or accomplish everyday tasks like driving or using a cell phone.

The umbrella term dementia encompasses a number of neurological conditions, including:

• Alzheimer’s disease
• dementia associated with Parkinson’s disease
• vascular dementia
• Pick’s disease (frontotemporal dementia)
• Creutzfeldt-Jakob disease

Most people begin to show signs of dementiaTrusted Source in their mid-60s(I'm 66), however, some can begin as early as their 30s.

There are a number of early warning signs that doctors look for when diagnosing dementia. These include:

1. loss of memory that disrupts everyday life(Nope)
2. confusion with dates, times, and places(Nope)
3. difficulty managing normal tasks at home or work(Nope)
4. communication issues(Nope)
5. constantly misplacing items(Nope)
6. balance issues(The only time I fall is when I'm doing extremely challenging walks in nature)
   
7. difficulty solving problems(Nope)
8. withdrawn from social activities(I do massive amounts of social activities)
   
9. mood and/or personality changes(Nope, I'm eternally happy)
   
10. decreased judgment skills(Nope)

Signs 9 years before diagnosis

According to Dr. Tim Rittman, senior clinical research fellow in the Department of Clinical Neurosciences at the University of Cambridge, honorary neurology consultant at the Addenbrookes Memory Clinic in Cambridge, and senior author of this study, the team was trying to find how early it is possible to detect changes in memory, thinking, and day-to-day function that might be caused by a progressive brain disease, such as Alzheimer’s disease, Parkinson’s disease, and other similar conditions.

“One of the criticisms of clinical trials of drugs to target progressive brain diseases is that they have captured disease too late, at a time when it may not be possible to change the course of (the) disease,” he explained to Medical News Today. “It has not been clear how early it is possible to detect changes in the brain in these diseases.”

“Some evidence from genetic types of dementia suggests that changes happen years before the diagnosis is made, but until now it has been much more difficult to prove this is true for non-genetic types of dementia and other progressive brain diseases,” Dr. Rittman continued.

“If we can catch progressive brain diseases at the earliest stage we might be able to stop them (from) progressing with changes in lifestyle or new drugs.”
— Dr. Tim Rittman

For this study, Dr. Rittman and his team used data from the UK Biobank, which includes medical information from more than 500,000 people recruited between 2006–2010 at ages 40–69.

Upon analysis, researchers found those who eventually developed Alzheimer’s disease scored poorly on tests related to problem-solving tasks, reaction times, remembering lists of numbers, pair matching, and prospective memoryTrusted Source than people who did not develop dementia. Participants took these tests five to nine years before receiving a dementia diagnosis.

People who developed Alzheimer’s were more likely to have had a fall than those who did not. And researchers found for most dementia conditions studied, people reported poorer overall health at baseline.

Helping prevent future decline

When discussing the next steps for this research, Dr. Rittman said in this study his team used only memory and thinking tests and surveys about people’s day-to-day functions. Including extra tests, such as brain scansTrusted Source or blood tests, might allow them to even better predict a person’s risk of dementia.

“At the moment, we would like to see people use these tests to select people for clinical trials of drugs to slow or stop progressive brain diseases,” he said.

“We would also like to see these tests choose people for diet and lifestyle change to try and prevent future decline in progressive brain diseases to preserve memory, thinking, and mobility,” he added.

Preventive strategies for dementia

Medical News Today also spoke with Dr. Scott Kaiser, a geriatrician and director of geriatric cognitive health for the Pacific Neuroscience Institute in Santa Monica, CA, about this study.

He found this study “validating and important” because although clinicians already know certain things like biomarkersTrusted Source, PET scansTrusted Source, and blood tests can show pathological changes of neurodegeneration many years ahead of symptoms, this study shows there are more subtle symptoms that could also be predictive.

“This is really important because if we could better identify those who are at risk of developing dementia and other neurodegenerative conditions, we have a better chance of intervening early to do something about it. And that can be intervention through lifestyle changes, through changes of managing other known risk factors like vascular risk factors (such as) high blood pressureTrusted Source. And it also can help us better select people for clinical trials to study new potential treatments.”
— Dr. Scott Kaiser

“This is the key — identifying people early so that we can intervene early and really begin to engage true preventive strategies,” he added.

When it comes to the next steps for this research, Dr. Kaiser said he would like to see additional refinement to have a strong predictive risk model where doctors can detect people who are at higher risk earlier and route them into supportive programs to help reduce their risks, such as exerciseTrusted Source programs and nutritional supportTrusted Source.

“There have been successful interventions where in targeting those known risk factors, we can actually reduce people’s risk significantly, bordering on just potentially preventing altogether some cases from ever occurring,” Dr. Kaiser said.

“One of the real keys to the success of those kinds of interventions is finding those people (with) that hidden and rising risk. … And we need that — we’re looking at 150 million people living with dementia in the coming decades if we don’t find effective ways to prevent or otherwise modify this disease course,” he added.