Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Showing posts with label sharp wave ripples. Show all posts
Showing posts with label sharp wave ripples. Show all posts

Wednesday, November 20, 2019

Predicting Alzheimer’s Disease-Like Memory Loss before It Strikes

You will need this so you are going to have to demand some competence from your doctors and stroke hospital to make sure human testing is done. Then if you are really lucky your doctor will have protocols that prevent dementia/Alzheimers.  

Your chances of getting dementia.

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 

5. Parkinson’s Disease May Have Link to Stroke March 2017 

 I'm doing this.
Dementia prevention 19 ways
Don't follow me, I'm not medically trained.

 

Predicting Alzheimer’s Disease-Like Memory Loss before It Strikes 

 


For a person with Alzheimer’s disease, there’s no turning back the clock. By the time she begins to experience memory loss and other worrisome signs, cognitive decline has already set in. And decades of clinical trials have failed to produce treatments that could help her regain her memory.
Today, researchers at Gladstone Institutes are approaching this devastating disease from a different angle. In a new study published in Cell Reports, they demonstrate that particular patterns of brain activity can predict far in advance whether a young mouse will develop Alzheimer’s-like memory deficits in old age.
“Being able to predict deficits long before they appear could open up new opportunities to design and test interventions that prevent Alzheimer’s in people,” said Gladstone Senior Investigator Yadong Huang, senior author of the study.
The new work builds on a 2016 study of mice engineered to carry the gene for apolipoprotein E4 (ApoE4). Carrying the ApoE4 gene is associated with an increased risk—but not a guarantee—of Alzheimer’s disease in humans. As they age, ApoE4 mice often, but not always, develop signs of memory loss similar to those seen in people with Alzheimer’s.
In the previous study, Huang and his team investigated a type of brain activity called sharp-wave ripples (SWRs), which play a direct role in spatial learning and memory formation in mammals. SWRs occur when the brain of a resting mouse or human rapidly and repeatedly replays a recent memory of moving through a space, such as a maze or a house.
“SWRs have two important measurable components: abundance and short gamma (SG) power,” said Emily Jones, PhD, lead author of the new study and recent graduate of UC San Francisco’s (UCSF) Biomedical Sciences Graduate Program. “Broadly, SWR abundance predicts how quickly an ApoE4 mouse can learn and memorize how to get through a maze, and SG power predicts how accurate that memory will be.”
The earlier study revealed that aging ApoE4 mice have lower SWR abundance and weaker SG power than seen in healthy aging mice. Based on those results, Jones and her colleagues hypothesized that measuring SWR activity could predict the severity of demonstrable memory problems in ApoE4 mice during aging.
To test this idea, the researchers first recorded SWR activity in aging ApoE4 mice at rest. One month later, they had the mice perform spatial tasks to test their memory. They found that mice with fewer SWRs and lower SG power were indeed more likely to have worse spatial memory deficits.
“We actually successfully replicated this experiment 2 years later with different mice,” said Huang, who is also a professor in the Departments of neurology and pathology at UCSF. “What was striking is that we were able to use the results from the first cohort to predict with high accuracy the extent of learning and memory deficits in the second cohort, based on their SWR activity.”
Even more striking were the unexpected results of the team’s next experiment.
The researchers were curious how SWR activity evolves over a mouse’s lifetime, which no one had previously investigated. So, they periodically measured SWRs in ApoE4 mice from an early age—long before memory deficits appeared—through middle age, and into old age.
“We thought that, if we got lucky, the SWR measurements we took when the mice were middle aged might have some predictive relationship to later memory problems,” Jones said.
Yadong Huang and Emily Jones speak at a computerEmily Jones (left), first author of the study, and Yadong Huang (right)
Surprisingly, the analysis revealed that deficits in SWR abundance and SG power at an early age predicted which mice performed worse on memory tasks 10 months later—the equivalent of 30 years for a human.
“We were not betting on these results, the idea that young mice with no memory problems already have the seed of what’s going to lead to deficits in old age,” Jones said. “Although we would love to, but we thought it would be ridiculous to be able to predict so far in advance.”
Since SWRs are also found in humans, these findings suggest that SWR abundance and SG power could potentially serve as early predictors of Alzheimer’s disease, long before memory problems arise.
As a next step toward evaluating that possibility, Huang will work with colleagues at the UCSF Memory and Aging Center to determine whether SWRs in Alzheimer’s patients show deficits in abundance and SG power similar to those seen in mouse models of the disease.
“A major advantage of this approach is that researchers have recently developed a noninvasive technique for measuring SWRs in people, without implanting electrodes in the brain,” Huang said.
If SWRs are indeed predictive of Alzheimer’s in humans, measuring them could boost research and drug development efforts in two important ways. First, they could be used to select participants for clinical trials testing new drugs to stave off Alzheimer’s. Enrolling patients who already show SWR deficits would enhance the trials’ statistical power. Second, SWR measurements could be taken repeatedly and noninvasively, enabling researchers to test drug effects over time, even before memory deficits appear.
Huang emphasizes the value of SWRs as a functional predictor, one that directly measures the decline in brain function seen in Alzheimer’s, as opposed to a pathological change that only appears as a result of the underlying disease.
“I feel strongly that Alzheimer’s research should not just focus on pathology, but use functional alterations like SWR deficits to guide research and drug development,” he said. “Our new findings support this kind of approach.”
The new study is just one facet of Gladstone’s extensive Alzheimer’s research program. “Gladstone provides a unique setting that makes it possible to do the kind of translational research necessary to improve understanding and treatment of this disease,” Huang said.
About the Research Project
Other authors include: Anna Gillespie, PhD, from UCSF, Seo Yeon Yoon from Gladstone, and Loren Frank, PhD, from UC San Francisco and the Howard Hughes Medical Institutes.

Sunday, January 1, 2017

The Rhythm That Makes Memories Permanent

You will need to ask your doctor how to use this news to improve your memory post-stroke. Don't just take tests proving your memory is bad, that is fucking stupid. DEMAND your doctor give you EXACT protocols to improve memory. Anything less is pure incompetency.
http://neurosciencenews.com/memory-synapses-swrs-5828/

Summary: Sharp wave ripples, brain waves important for memory consolidation, are influenced by synaptic inhibition, researchers report.
Source: Institute of Science and Technology Austria.
Scientists at IST Austria identify mechanism that regulates rhythmic brain waves — inhibition at synapses is the key to make memories permanent.
Every time we learn something new, the memory does not only need to be acquired, it also needs to be stabilized in a process called memory consolidation. Brain waves are considered to play an important role in this process, but the underlying mechanism that dictates their shape and rhythm was still unknown. A study now published in Neuron shows that one of the brain waves important for consolidating memory is dominated by synaptic inhibition.
So-called sharp wave ripples (SWRs) are one of three major brain waves coming from the hippocampus. The new study, a cooperation between the research groups of Professors Peter Jonas and Jozsef Csicsvari at the Institute of Science and Technology Austria (IST Austria), found the mechanism that generates this oscillation of neuronal activity in mice. “Our results shed light on the mechanisms underlying this high-frequency network oscillation. As our experiments provide information both about the phase and the location of the underlying conductance, we were able to show that precisely timed synaptic inhibition is the current generator for sharp wave ripples.” explains author Professor Peter Jonas.
When neurons oscillate in synchrony, their electrical activity adds together so that measurements of field potential can pick them up. SWRs are one of the most synchronous oscillations in the brain. Their name derives from their characteristic trace when measuring local field potential: the slow sharp waves have a triangular shape with ripples, or fast field oscillations, added on. SWRs have been suggested to play a key role in making memories permanent. In this study, the researchers wanted to identify whether ripples are caused by a temporal modulation of excitation or of inhibition at the synapse, the connection between neurons. For Professor Jozsef Csicsvari, a pooling of expertise was crucial in answering this question: “SWRs play an important role in the brain, but the mechanism generating them has not been identified so far – probably partly because of technical limitations in the experiments. We combined the Jonas group’s experience in recording under voltage-clamp conditions with my group’s expertise in analyzing electrical signals while animals are behaving. This collaborative effort made unprecedented measurements possible and we could achieve the first high resolution recordings of synaptic currents during SWR in behaving mice.”
The neuroscientists found that the frequency of both excitatory and inhibitory events at the synapse increased during SWRs. But quantitatively, synaptic inhibition dominated over excitation during the generation of SWRs. Furthermore, the magnitude of inhibitory events positively correlated with SWR amplitude, indicating that the inhibitory events are the driver of the oscillation. Inhibitory events were phase locked to individual cycles of ripple oscillations. Finally, the researchers showed that so-called PV+ interneurons – neurons that provide inhibitory output onto other neurons – are mainly responsible for generating SWRs.
a graph.
During sharp wave ripples (shown on the top) the inhibitory conductance (blue curve) has a much higher amplitude than the excitatory conductance (red curve). This shows that inhibition is the underlying mechanism that creates the brain wave. NeuroscienceNews.com image is credited to IST Austria.
The authors propose a model involving two specific regions in the hippocampus, CA1 and CA3. In their model SWRs are generated by a combination of tonic excitation from the CA3 region and phasic inhibition within the CA1 region. Jian Gan, first author and postdoc in the group of Peter Jonas, explains the implications for temporal coding of information in the CA1 region: “In our ripple model, inhibition ensures the precise timing of neuronal firing. This could be critically important for preplay or replay of neuronal activity sequences, and the consolidation of memory. Inhibition may be the crucial player to make memories permanent.”
About this neuroscience research article
Funding: The study was funded by Fond zur Förderung der Wissenschaftlichen Forschung, European Research Council.
Source: Peter Jonas – Institute of Science and Technology Austria
Image Source: NeuroscienceNews.com image is credited to IST Austria.
Original Research: Full open access research for “Phase-Locked Inhibition, but Not Excitation, Underlies Hippocampal Ripple Oscillations in Awake Mice In Vivo” by Jian Gan, Shih-ming Weng, Alejandro J. Pernía-Andrade, Jozsef Csicsvari, and Peter Jonas in Neuron. Published online December 29 2016 doi:10.1016/j.neuron.2016.12.018