Motor imagery enhances swallowing motor cortex excitability and activates sensorimotor regions: a TMS and fNIRS study

 Will your competent? doctor bring this intervention into the hospital? NO? Why not? Although first they have to initiate research on stroke subjects.

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

Motor imagery enhances swallowing motor cortex excitability and activates sensorimotor regions: a TMS and fNIRS study

• Tuo Lin,
• Gengbin Chen,
• Yaojian Lao,
• Wanqi Li,
• Guangqing Xu &
• Yue Lan 

We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.

Abstract

Background

Action observation (AO) and motor imagery (MI) represent promising, non-invasive strategies for promoting neuroplasticity in motor rehabilitation by engaging the shared neural substrates of actual movement. However, their translation to swallowing rehabilitation, particularly for neurogenic dysphagia, lacks a robust neurophysiological foundation. A critical barrier is the absence of direct, multimodal evidence comparing how swallowing-specific static AO (SAO), dynamic AO (DAO), and MI differentially engage the cortical swallowing network. Specifically, their immediate effects on corticobulbar excitability and hemodynamic activation within key sensorimotor regions remain unquantified and poorly contrasted, limiting the rationale for their targeted clinical application.

Objective

This study employed a dual-modal neuroimaging approach to precisely quantify and compare the immediate neurophysiological effects of SAO, DAO, and MI on the human swallowing sensorimotor system. We aim to evaluate their modulatory effects on bilateral suprahyoid motor cortical excitability and intracortical inhibitory/facilitatory circuitry using transcranial magnetic stimulation (TMS), and map their hemodynamic activation patterns within core sensorimotor cortices compared to motor execution (ME) using functional near-infrared spectroscopy (fNIRS).

Methods

Thirty-two healthy adults underwent integrated assessments using transcranial magnetic stimulation (TMS) and functional near-infrared spectroscopy (fNIRS). TMS measured motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) in bilateral suprahyoid motor cortices during rest, SAO, DAO, and MI. fNIRS mapped hemodynamic changes in dorsal/ventral precentral (dPreCG/vPreCG) and postcentral gyri (dPoCG/vPoCG), superior/middle frontal gyri (SFG/MFG) during swallowing-specific SAO, DAO, MI and ME.

Results

MI reduced bilateral SICI and increased left ICF, concurrently activating bilateral dPoCG, left SFG/MFG, and right dPreCG/vPreCG/vPoCG—regions overlapping with ME-activated networks (bilateral vPreCG/vPoCG/MFG), with left MFG, right vPreCG/vPoCG as coactivating areas. In contrast, DAO reduced left SICI but elicited no hemodynamic activation, while SAO showed no significant effects.

Conclusion

MI enhances the excitability of the swallowing motor cortex and activates the key sensorimotor cortical areas governed ME of swallowing. MI shows greater superiority over AO and may become a promising effective rehabilitation strategy for neurogenic dysphagia.

Trial registration Chinese Clinical Trial Registry, ChiCTR2000036715. Registered on 24 August 2020, https//www.chictr.org.cn/bin/home.

Blood-activating, depression-relieving formula alleviates post-stroke depression: mechanistic insights from network pharmacology and microglial validation

 Why are you researching treating depression rather than preventing it in the first place? 

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

100% recovery protocols would solve that problem. You'll want 100% recovery when you are the 1 in 4 per WHO that has a stroke

Better start working on that goal now.

And your board of directors is so incompetent they don't recognize incompetence in their staff!

Blood-activating, depression-relieving formula alleviates post-stroke depression: mechanistic insights from network pharmacology and microglial validation

• N

  Na Zhao

• L

  Lumi Zhang

• W

  Wei Li

• Y

  Yiru Wang

• Z

  Zhengyu Zhu

• 

  Zhimin Wu *

• Department of Neurology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Zhejiang, China

Abstract

Introduction: 

Post-stroke depression (PSD) is common and disabling, yet mechanism-based, multi-target therapies that jointly curb neuroinflammation and support cell survival are scarce. We evaluated a Blood-Activating, Depression-Relieving (BADR) herbal formula for effects on PSD-relevant molecular hubs and microglial phenotypes.

Methods: 

BADR constituents from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were standardised and mapped to human protein targets. Target-disease interaction networks were assembled in Search Tool for the Retrieval of Interacting Genes/Proteins, clustered with Molecular Complex Detection, and functionally annotated via Kyoto Encyclopedia of Genes and Genomes Orthology-Based Annotation System (KEGG/GO). For experimental validation, BV2 microglia were activated with lipopolysaccharide (LPS; 24 h) and co-treated with BADR within a pre-established non-cytotoxic range; dexamethasone (1 μM) served as comparator. Outcomes included cytokines (IL-1β, TNF-α, IL-6; enzyme-linked immunosorbent assay), expression of selected nodes (EGFR, STAT3, JUN, PIK3CA, BCL2; quantitative real-time polymerase chain reaction/western blot), viability (Cell Counting Kit-8), and apoptosis (flow cytometry).

Results: 

Network analysis highlighted two dense modules enriched for PI3K-AKT, JAK–STAT, and neuroactive-ligand signaling. Hubs included EGFR, AKT1, STAT3, JUN, PIK3CA, and BCL2, with EGFR, STAT3, PIK3CA, JUN, and BCL2 prioritised for cellular validation based on topology, pathway relevance, and compound-target connectivity. In BV2 cells, BADR attenuated LPS-induced IL-1β, TNF-α, and IL-6 surges, improved viability, and reduced total apoptosis, with directionally comparable effects to dexamethasone. Mechanistically, BADR down-regulated EGFR/JUN/STAT3/PIK3CA and restored BCL2 at transcript and protein levels.

Conclusion: 

By converging network-level predictions with microglial phenotyping, the formula exerts coordinated anti-inflammatory and pro-survival effects centred on the EGFR-STAT3-PI3K nodes in a PSD-relevant context. These data provide a mechanistic rationale for further phosphorylation-level and in vivo validation toward multi-target PSD therapeutics.

More at link.

Why Some Brains Stay Sharp Despite Alzheimer’s-Related Changes by mindbodygreen

 Has your competent? doctor translated this into AN EXACT PROTOCOL, So you won't get Alzheimers? NO? Why not?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

And your board of directors is so incompetent they don't recognize incompetence in their staff!

 

Why Some Brains Stay Sharp Despite Alzheimer’s-Related Changes

ECT Reprograms Adult Neurons into a Youthful State

 

Have your competent? doctor and hospital initiate research/human testing that finishes the job and delivers 100% recovery protocols! Why can't that be done?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

And your board of directors is so incompetent they don't recognize incompetence in their staff! 

ECT Reprograms Adult Neurons into a Youthful State

Summary: Researchers engineered a highly specialized patterned stimulation protocol called REPOPS (Repeated Electroconvulsive-like Patterned Optical/Electrical Stimulation) in murine models to precisely mirror the neural activation patterns of ECT. The empirical data unmasked a stunning structural transformation: intensive ECT-like stimulation coaxes fully mature, non-dividing adult neurons to undergo an active process of cellular dematuration.

By entering a state of nuclear reprogramming driven unexpectedly by the cell-cycle protein Cyclin B, mature neurons fundamentally reshape their identity, winding back their genetic clocks to resemble highly plastic, early postnatal developmental states.

Key Facts

• The Cellular Dematuration Framework: Genome-wide transcriptomic profiling unmasked that REPOPS forces mature, fully differentiated adult neurons to suppress their adult genetic markers. Instead, they reactivate gene expression blueprints that match early postnatal development. Widespread genome-wide chromatin mapping confirmed long-lasting structural changes in chromatin accessibility, proving this youthful state is epigentically locked in place for over a month.
• Unexpected Post-Mitotic Cell Cycle Re-entry: The most jaw-dropping molecular discovery was that adult neurons, cells that are strictly post-mitotic and can never divide again, suddenly expressed gene networks typically reserved exclusively for the G2/M division phase of proliferating cells. The neurons displayed clear physical hallmarks of mitosis, including widespread histone phosphorylation, the breakdown of the nuclear lamina protective skin, and pronounced chromatin condensation.
• Cyclin B Isolated as the Molecular Driver: To prove this cell-cycle activation was driving the structural shift rather than acting as a random byproduct, Miyakawa’s lab deployed targeted genome-editing technology. Mice engineered to lack Cyclin B (the core molecular key required to cross the G2/M phase boundary) exhibited a total failure of nuclear reprogramming and showed zero behavioral improvements following stimulation, identifying Cyclin B as the absolute gatekeeper of ECT efficacy.
• The “Intermediate State” of Heightened Plasticity: Calcium-flux live imaging in actively behaving mice revealed that REPOPS does not simply act as an on/off switch for neural circuits. Instead, it coaxes the brain into a unique “intermediate state” of intense plasticity. The network completely shifted how it encoded information, selectively suppressing spatial coding maps while heavily boosting speed-related navigation tracking for over two weeks.
• Human Validation in the Dentate Gyrus: Transitioning from mice to humans, the team’s reanalysis of postmortem brain tissue from deceased patients with major depression revealed an identical biological footprint. Individuals who had undergone ECT treatments prior to their passing displayed the exact same immature-like gene expression patterns within the dentate gyrus (the primary gateway of the hippocampus) compared to non-ECT patients, confirming human translation.
• A Double-Edged Sword for Neurology: Professor Miyakawa emphasizes that this newly uncovered intermediate state is a powerful, highly flexible biological tool. While this extreme boost in structural plasticity is precisely what allows an injured brain to break free from severe depression, the team warns that if the exact same nuclear reprogramming occurs under incorrect or overly aggressive conditions (such as advanced neurodegeneration or epilepsy), it could spin out of control and drive severe pathology.
• Source: Fujita Health University

Nearly 90 years after Ugo Cerletti and Lucio Bini introduced electroconvulsive therapy (ECT), brain stimulation therapies such as ECT and Repetitive Transcranial Magnetic Stimulation (rTMS) are common in psychiatry because they are highly effective for treating depression and schizophrenia, yet their cellular mechanisms remain poorly understood.

The team introduced REPOPS, a form of patterned stimulation in mice designed to mimic key features of ECT-like neuronal activation.

Mice subjected to REPOPS showed increased locomotor activity and reduced depression-like behavior, revealing stimulation-induced lasting behavioral changes similar to ECT-like states. At the cellular level, the stimulation induced a state of cellular dematuration, in which adult neurons had gene expression patterns resembling those seen in early postnatal development.

Stimulation for three days caused only transient changes, while ten-day stimulation resulted in a stable dematuration state that persisted for over a month. Genome-wide chromatin mapping revealed widespread and persistent changes in chromatin accessibility, providing molecular evidence for the durability of this state.

A reanalysis of postmortem brain RNA-seq data from patients with mood disorders showed that ECT-treated individuals exhibited a similar immature-like gene expression pattern in the dentate gyrus compared to non-ECT-treated patients, suggesting that similar immature-like changes may also occur in the human dentate gyrus after ECT.

Surprising Emergence of Cell Cycle Re-entry in Mature Neurons

A gene expression analysis revealed an unexpected finding: despite being post-mitotic (cells that no longer divide), neurons following REPOPS exhibited gene expression patterns characteristic of the G2/M phase of the cell cycle in dividing cells, accompanied by nuclear hallmarks of mitosis — histone phosphorylation, disruption of the nuclear lamina, and chromatin condensation.

These molecular and structural changes suggested nuclear reprogramming. Using genome-editing technology, the researchers demonstrated that mice lacking Cyclin B, a key molecular regulator of the G2/M phase transition, showed less nuclear reprogramming and behavioral changes, identifying it as a driver of cellular state triggered by neuronal stimulation.

An Intermediate State of Heightened Plasticity

The researchers next asked how nuclear reprogramming affects neuronal function. They used microscopic imaging of calcium fluxes, a proxy for neuronal activity, in behaving mice. Curiously, REPOPS did not simply turn neuronal activity on or off. Instead, it produced a patterned shift in how neurons encode different types of information — spatial coding was suppressed while speed-related coding was enhanced — that persisted for over two weeks.

Taken together, these molecular, nuclear structural, and functional findings led the researchers to propose that the dematured cellular state induced by ECT-like stimulation represents an “intermediate state” of high plasticity — neither the normal mature state nor the fully immature one — where the specific configuration may depend on how strongly, how often, and under what conditions neuronal activity is applied. The plasticity supporting therapeutic effects in depression could, under different conditions such as epilepsy or neurodegeneration, contribute to pathology instead.

“Nuclear reprogramming — the ability of neurons to fundamentally reshape their own identity — is a candidate mechanism we had not previously considered,” said Prof. Miyakawa. “These findings provide a new cellular framework for thinking about how durable changes in neural function can arise, and they offer a potential route to improved therapies.”

Key Questions Answered:

Q: How can a cell that is “post-mitotic” start using cell-cycle genes without turning into a tumor or dividing?

A: This is what makes Professor Miyakawa’s discovery an absolute shock to traditional biology. For decades, neuroscience has taught that once a neuron reaches maturity, it becomes permanently post-mitotic, meaning it locks its cell-division machinery away forever. If a mature neuron attempts to force its way through cell division, it typically triggers immediate cell death. The REPOPS framework proves that neurons can cleverly hijack the early stages of this division machinery (the G2/M phase) without actually completing the physical split. They use proteins like Cyclin B to intentionally soften their internal structure, break down their nuclear lining, and loosen up their packed DNA. They aren’t trying to duplicate; they are using the tools of cell division to perform a massive, structural house clean, allowing them to rapidly rewrite their active genes.

Q: What is “cellular dematuration,” and why does winding back a neuron’s clock cure severe depression?

A: Think of severe, chronic depression like a deep, frozen rut in a muddy road. Over months or years of illness, the adult brain’s neural connections become incredibly rigid, locking negative emotional paths in place. “Cellular dematuration” is the biological equivalent of melting that frozen mud back into soft clay. By forcing adult neurons to temporarily express genes that look exactly like those found in a newborn baby’s brain, ECT-like stimulation strips away this unhealthy structural rigidity. The neuron doesn’t lose its long-term identity, but it enters an open, highly sensitive “intermediate state” of intense plasticity. This sudden malleability gives the brain a vital window to wipe away the rigid, depressive neural ruts and wire up entirely new, healthy pathways.

Q: If this treatment induces such massive brain changes, why don’t patients lose all their memories or cognitive function?

A: The live calcium-flux imaging in behaving models provided a fascinating answer to this concern. The treatment does not act like a chaotic eraser that turns off neural signaling across the board. Instead, entering this high-plasticity intermediate state causes the brain to elegantly pivot how it processes information. For instance, the researchers observed that while the neurons temporarily suppressed their spatial layout maps, they simultaneously cranked up their sensitivity to tracking speed. The brain remains active and functional, but its processing modes are temporarily shifted. Because the study showed these changes spontaneously stabilize and return to an adult baseline after a month, it confirms that the brain undergoes a structured, temporary transition rather than permanent damage.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this neuroscience research news

Author: Hisatsugu Koshimizu
Source: Fujita Health University
Contact: Hisatsugu Koshimizu – Fujita Health University
Image: The image is credited to Neuroscience News

Original Research: Open access.

“Repetitive Neuronal Activation Regulates Cellular Maturation State via Nuclear Reprogramming” by Tomoyuki Murano, Hideo Hagihara, Katsunori Tajinda, Keizo Takao, Yoshihiro Takamiya, Kaoru Katoh, Alfred J. Robison, Mitsuyuki Matsumoto, Masakazu Namihira & Tsuyoshi Miyakawa. Nature Communications
DOI:10.1038/s41467-026-74202-w

Prediction models for post-stroke delirium: a systematic review with an exploratory meta-analysis of predictors

 

Why are your predicting failure to recover RATHER THAN DELIVERING RECOVERY?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

You're all fired! You need to create EXACT RECOVERY PROTOCOLS! 

You've known of the need for years and delivered nothing!  Take a hike!

39% post stroke delirium (4 posts to July 2021)

Prediction crapola like this does nothing to get survivors recovered! Your comeuppance when you have a stroke and don't recover will be a bitter pill for you to swallow.

Prediction models for post-stroke delirium: a systematic review with an exploratory meta-analysis of predictors

• W

  Weiya Ma

• 

  Sumin Ma † *

• Q

  Qiaomin Tang † *

• Y

  Yuanyuan Sun

• C

  Chen Hu

• Department of Nursing, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China

Abstract

Objective: 

To systematically identify and synthesize predictors of post-stroke delirium (PSD) derived from existing prediction models, and to assess the methodological quality of these studies using PROBAST.

Methods: 

A comprehensive systematic search was conducted in nine databases from inception to April 2026. Studies developing or validating prediction models for PSD were included. Data extraction was guided by the CHARMS checklist. Methodological quality and risk of bias were assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Meta-analysis was performed to pool the effect sizes of predictors and the area under the receiver operating characteristic curve (AUC).

Results: 

Sixteen studies (24 models) with sample sizes ranging from 100 to 14,475 were included. Model discrimination was moderate to good, with reported AUC values ranged from 0.72 to 0.94. The meta-analytic pooled AUC was 0.83 (95% Confidence interval: 0.81–0.85). Age, NIHSS (National Institutes of Health Stroke Scale score), neutrophil-to-lymphocyte ratio, visual impairment, and infection were identified as common significant predictors. PROBAST assessment revealed a high overall risk of bias in all studies, primarily due to methodological shortcomings in the analysis domain. Calibration was assessed in six studies with acceptable performance, whereas clinical utility was rarely evaluated.

Conclusion: 

This study highlights several important predictors of PSD. However, due to the high risk of bias, the reliability of existing models remains uncertain. Although the pooled AUC of 0.84 suggests moderate to good discrimination, its performance in individual clinical settings may vary markedly. Future studies should adhere to unified PSD diagnosis criteria, employ robust validation strategies, and explore advanced modeling techniques to improve model reliability and clinical utility.

More at link.

Modified small vessel disease score as the top predictor of stroke outcome after thrombectomy: a CT-based machine learning study

 

Why are your predicting failure to recover RATHER THAN DELIVERING RECOVERY?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

You're all fired! You need to create EXACT RECOVERY PROTOCOLS! 

Prediction crapola like this does nothing to get survivors recovered! Your comeuppance when you have a stroke and don't recover will be a bitter pill for you to swallow.

Modified small vessel disease score as the top predictor of stroke outcome after thrombectomy: a CT-based machine learning study

• 

  Thiago Oscar Goulart 1† *

• 

  Rui Kleber do Vale Martins-Filho 2

• 

  Millene Rodrigues Camilo 2

• 

  Daniel Giansante Abud 2

• 

  Octávio Marques Pontes-Neto 2

• 1. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States

• 2. Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Abstract

Background: 

Mechanical thrombectomy (MT) improves outcomes in ischemic stroke (IS) due to large vessel occlusion (LVO), but ~50% of patients fail to achieve functional independence.

Objectives: 

We investigated whether cerebral small vessel disease (cSVD), assessed by the modified Small Vessel Disease (mSVD) score and Brain Frailty Score (BFS), outperforms individual CT markers in predicting 90-day outcomes after MT.

Design: 

Prospective cohort with retrospective analysis.

Methods: 

We included 351 patients with anterior circulation LVO treated with MT. Admission CT was used to score cSVD markers (leukoaraiosis, atrophy, lacunes) and compute mSVD and BFS. Eight logistic regression models and a Random Forest algorithm were used to predict poor outcome [modified Rankin Scale (mRS) 3–6]. Model performance was evaluated using AUC-ROC and compared via DeLong tests.

Results: 

Poor outcomes were associated with older age, higher NIHSS, systolic blood pressure, glycemia, and more severe leukoaraiosis and atrophy. Severe mSVD (score = 3) independently predicted poor outcomes (OR = 3.267; CI: 1.731–6.168; p = 0.009). mSVD outperformed BFS and individual CT markers (AUC = 0.904 vs. 0.889/0.898; DeLong p < 0.05) and ranked as the top predictor in Random Forest (importance = 42.05). Treatment efficacy declined with increasing mSVD: the probability of a favorable outcome was 15.53% and poor outcome was 84.47% for mSVD = 3, compared to 89.23% and 10.77%, respectively, for mSVD = 0. A secondary model incorporating 24h NIHSS and hemorrhagic transformation improved discrimination (AUC = 0.954), but mSVD remained a key independent predictor.

Conclusions: 

In this prospective study in a middle-income country, mSVD score was the strongest predictor of post-thrombectomy outcome, outperforming BFS and isolated imaging markers. While cSVD does not contraindicate MT, it reflects reduced cerebrovascular resilience. Integrating mSVD into baseline CT evaluation may enhance risk stratification and treatment guidance.

More at link.

Drug-induced ‘brain freeze’ could slow stroke damage, study finds

 

Have your competent? doctor and hospital initiate research that finishes the job and delivers 100% recovery protocols! Why can't that be done?

Laziness? Incompetence? Or just don't care? NO leadership? NO strategy? Not my job? Not my Problem!

Drug-induced ‘brain freeze’ could slow stroke damage, study finds

Drug-induced hypometabolism may slow stroke-related brain damage, according to early research involving animals and people.

The experimental treatment uses two existing medicines to reduce metabolism and create a state resembling hypothermia.

Tests in mice and rhesus monkeys found that the approach protected brain tissue, while an early trial involving 32 stroke patients reported no notable side effects.

The treatment combined chlorpromazine, an antipsychotic medicine, with the sedative promethazine. The combination was known as C+P.

The small human trial found no significant improvements in the amount of brain damage or participants’ ability to carry out daily activities independently.

Further studies will be needed to establish what benefits the treatment might offer people who have experienced strokes.

The research also provided more information about the role of hypometabolism, when the body uses less energy, in the protective effects associated with hypothermia.

Dr Eric Landsness, assistant professor of neurology at Washington University School of Medicine in St Louis, was not involved in the research.

He said: “What’s exciting about this study is that it’s clear that it’s not just the hypothermia, but it’s the hypometabolism.”

The researchers tested C+P as a treatment for acute ischaemic stroke, which occurs when blood flow to the brain is suddenly blocked.

Ischaemic strokes account for more than 85 per cent of strokes. The acute form is a medical emergency involving the sudden loss of blood flow and neurological function.

Restoring blood flow through reperfusion treatment can cause further damage through processes that began while the brain was deprived of blood.(That's called the neuronal cascade of death and will kill off hundreds of millions of neurons in the first week!; noted by Rockefeller University back in 2008! And you incompetently don't know that?)

Dr Patrick Lyden, professor of physiology and neuroscience, neurology and neurosurgery at the University of Southern California Keck School of Medicine, was not involved in the study.

He said: “You can get significant injury from a lot of processes that were set in motion during the ischaemia.”

Researchers have previously examined whether hypothermia could protect brain tissue from damage caused by both ischaemia and the return of blood flow.

Lyden described hypothermia as “one of the most powerful ways of protecting the brain that we’ve ever studied in lab animals”.

He added: “It’s the standard by which all other brain protectants are measured.”

Hypothermia occurs when body temperature falls below 35°C.

Under normal circumstances, it can be dangerous because the cold may slow the heart and nervous system enough to cause cardiac and respiratory failure.

One theory behind its therapeutic effects is that cooling slows metabolism in a similar way to hibernation.

Lyden said slowing metabolism could also delay the process of brain-cell death.

Therapeutic hypothermia can protect the brain following cardiac arrest and is sometimes used to treat newborn babies with hypoxic-ischaemic encephalopathy.

This is a brain injury caused by reduced oxygen and blood flow around the time of birth.

However, studies of hypothermia in adults who have experienced strokes have produced less encouraging results.

The researchers suggested C+P might provide a more effective way to slow metabolism in stroke patients.

Earlier experiments found that the combination reduced inflammation in the nervous system in rodent stroke models, possibly through metabolic changes that were independent of hypothermia.

In the new study, researchers compared C+P with two other ways of lowering body temperature in mice: adenosine 5’-monophosphate and surface cooling using cold water and ice packs.

All three approaches caused hypothermia, but only C+P reduced overall oxygen consumption and energy expenditure, two signs of slower metabolism.

Landsness said the findings suggested metabolism was more than a secondary effect of hypothermia and should be studied in its own right.

In mice, C+P reduced the burning of sugar by the brain and brown fat, tissue that burns fuel to produce heat.

The treatment was also linked to less brain tissue damage and lower lactate accumulation after stroke. Lactate can build up and contribute to cell death.

Similar effects were observed in rhesus monkeys treated with C+P.

The small human trial suggested that the metabolic effects could also occur in people.

Patients given the highest dose had lower levels of metabolism-related proteins in their blood.

They were also the only participants to experience a significant fall in body temperature four hours after treatment, although their temperatures did not reach the level defined as hypothermia.

Temperatures did fall to that level in the mice and monkeys.

The participants also received standard treatments to restore blood flow to the brain.

C+P did not reduce the amount of brain damage detected 72 hours after treatment or improve independence in daily activities after 90 days.

The study authors, based at Capital Medical University in Beijing, did not respond to a request for comment.

They said future trials could establish whether C+P protects the brain following a stroke.

Although the treatment caused no notable side effects in the early human trial, Lyden said the medicines could potentially interact and cause muscle spasms, seizures or changes in heart rhythm.

He suggested that researchers may need to find other medicines capable of slowing metabolism without these potential risks.

Landsness said: “The new paper happened to fall upon a drug [combo] that happens to induce hypothermia and hypometabolism, but we don’t necessarily know why.”

Further research will be needed to understand how the drugs produce these effects.

Landsness’s laboratory is studying the neural circuits involved in hypothermia and hypometabolism, which could identify other targets for treatment.