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.

Targeted Brain Cooling Boosts LVO Recovery After Thrombectomy

 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!

Targeted Brain Cooling Boosts LVO Recovery After Thrombectomy

Targeted cooling to the brain during endovascular thrombectomy significantly improved functional outcomes in patients with large-vessel occlusion ischemic stroke.

Results of the CHILL-ART trial showed that cooling the brain by infusion of saline chilled to 4 °C led to a substantial increase in the number of patients who achieved a favorable functional outcome at 90 days.(Favorable to survivors is 100% RECOVERY; not your tyranny of low expectations where failure is considered success!)

“Even when we successfully remove the clot, many patients do not regain independence because of ongoing brain injury after blood flow is restored,” said principal investigator Zhi-Xin Huang, MD, Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China.(Yeah, that's called the neuronal cascade of death and will kill off hundreds of millions of neurons in the first week! I'd suggest billing your doctors and hospital $1000 a dead neuron, that would concentrate their minds!)

“Our findings show that targeted cooling delivered directly into the brain at the moment of reperfusion can meaningfully improve recovery without adding risk,” he noted.

Article Key Points

Targeted brain cooling during thrombectomy significantly improved recovery in ischemic stroke patients, with a 15% increase in functional independence at 90 days. The CHILL-ART trial suggests this approach is safe, effective, and easily implementable.

A second trial of a similar technique, FOCUS, also conducted in China, did not show a significant benefit, but functional outcomes trended in a positive direction in the intervention group, and there was a safety benefit with a reduction of any intracerebral hemorrhage (ICH) incidence at 24 hours.

“These findings validate the feasibility of selective intra-arterial cooling as an adjunctive therapy during endovascular thrombectomy. The marked decrease in any intracerebral hemorrhage indicates a potential protective effect on the blood-brain barrier and microvasculature, which may translate into clinical benefits,” FOCUS investigator, Shen Li, MD, Beijing Shijitan Hospital, Beijing, China, said.

The findings from both studies were presented on May 6 at the European Stroke Organization Conference (ESOC) 2026.

A Novel Approach

The CHILL-ART trial investigator, Raul Nogueira, MD, University of Pittsburgh School of Medicine, Pittsburgh, explained that hypothermia is known to be an effective neuroprotectant.

He noted that substantial data support the concept, but implementation has remained challenging. Systemic hypothermia has been associated with several drawbacks: It takes time to induce, can disrupt endovascular treatment workflows, and has been linked to significant adverse effects, including higher rates of pulmonary infection, potential coagulopathy and bleeding complications, and refractory shivering. As a result, this approach has not been widely pursued.

The CHILL-ART and FOCUS trials investigated a novel approach of inducing regional hypothermia by infusing chilled saline intra-arterially directly into the brain at the end of the thrombectomy procedure.

The intervention uses standard thrombectomy equipment and refrigerated saline, making it readily scalable in routine clinical practice without requiring specialized devices or additional training.

The CHILL-ART trial enrolled 262 patients across 26 comprehensive stroke centers. Participants within 24 hours of stroke onset were randomized to receive either thrombectomy plus intra-arterial infusion of 350 ml of cold saline (hypothermia group) or thrombectomy with room-temperature saline (control group). The saline was administered at 50ml pre-reperfusion and 300 ml directly after reperfusion.

The median patient age was 70 years, and the median National Institutes of Health Stroke Scale score was 14. The trial imposed no exclusion criteria based on baseline ASPECTS, and patients could be enrolled up to 24 hours after stroke onset. However, the median ASPECTS was high at 8, and treatment was initiated fairly early, at a median of between 5 and 6 hours after stroke onset, Nogueira reported.

15% Absolute Increase in Functional Independence

The study’s primary outcome, functional independence defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days, was achieved in 54.7% of patients in the hypothermia group compared with 39.8% in the control group (adjusted risk ratio, 1.36; 95% CI, 1.05 1.76; P =.018). This gives a number need to treat for one additional favorable outcome of 7.

Safety outcomes were comparable between groups, with no significant increase in symptomatic ICH (7.0% vs 9.0%) or 90-day mortality (13.3% vs 18.0%).

By combining reperfusion with targeted neuroprotection, the study introduces a promising new approach into acute stroke treatment, and these findings support broader adoption of intra-arterial hypothermia as an accessible, cost-effective strategy to reduce disability after stroke, the CHILL-ART trial investigators concluded.

However, the FOCUS trial results were not as favorable. The trial, conducted at 12 hospitals, enrolled 258 patients with anterior circulation large-vessel occlusion stroke who presented within 24 hours of symptom onset. Participants were randomized to receive either selective intra-arterial cooling plus endovascular thrombectomy or standard thrombectomy alone.

Results showed no significant difference in functional outcomes at 90 days between the two groups, with an adjusted common odds ratio of 1.16 (95% CI, 0.75-1.79; P = .51).

However, the safety results were encouraging, with a reduction in ICH rates in the cooling group with an adjusted risk difference of -0.174 (95% CI, -0.288 to -0.059; P = .003). There was no difference in the occurrence of symptomatic ICH or mortality between groups.

Easy and Inexpensive

Noguera pointed out that this approach is easy and inexpensive.

“We can use the typical neurovascular thrombectomy equipment, and it’s very easy to implement. You just need cold saline at 4 degrees,” he said.

Nogueira added that the results of the two studies were not necessarily contradictory, noting that both were only moderately sized trials. He suggested that the benefit seen in the CHILL-ART trial — a 15% absolute improvement in functional independence — was larger than expected, whereas the FOCUS trial produced more modest results than investigators had hoped for.

However, he noted that the mRS shift analyses from the two studies were actually similar, suggesting the apparent discrepancy may reflect differences in statistical power and sample size rather than fundamentally different findings.

“We are going to need more trials, larger numbers, and potentially meta-analyses, to really answer this question,” he said.

Still, Nogueira argued that the studies together provide important validation of the concept. “While we are going to need more data before changing guidelines, I think we have validated this concept here, and it is definitely a big step in the right direction,” he commented.

He added that regional brain cooling should now become a major focus of thrombectomy research because of its simplicity and apparent promise.

“I would say this regional cooling approach should be the biggest priority in thrombectomy research now because it’s so easy to implement, and we have a very strong signal of effectiveness,” Nogueira said.

Large Therapeutic Effect

Commenting on the CHILL-ART trial, Marieta Peycheva, MD, Medical University of Plovdiv, Plovdiv, Bulgaria, characterized the findings as “really amazing.”

She asked about safety, noting that there appeared to be slight increase in pneumonia in the intervention group.

Nogueira replied that the safety appears very good. He pointed out that rates of symptomatic ICH and mortality were numerically lower in the hypothermia groups in both trials, which he said was encouraging from a neurologic safety perspective.

Although pneumonia occurred slightly more often among patients receiving hypothermia, he emphasized that the cooling strategy produced minimal systemic effects because it was delivered over only a brief period rather than inducing prolonged whole-body hypothermia.

“Of course we need to look at that carefully in the future, but I think overall, in both trials we saw the same direction towards a benefit and very good safety.”

Commenting on the CHILL-ART trial, Peter Kelly, MD, University College Dublin, Dublin, Ireland, said the study really stood out.

“It showed a big therapeutic effect — a 15% absolute benefit in terms of 90-day functional independence, it looked very safe, and it involved just cooling a bag of saline to 4 °C.”

“This should certainly kick off a whole collection of new trials to try to confirm those really interesting results,” he added.

Both trials were investigator initiated. The authors reported having no relevant disclosures.

Debate heats up following contrasting trial results on brain cooling during stroke thrombectomy

 I guess you better hold off on having a stroke until this is solved. 

All my previous research posts on this suggested no useful intervention. Obviously no protocols were ever written on hypothermia so everyone is still shooting in the dark. The result being that survivors are still screwed with no consequences to the doctors who haven't written up protocols on this. Don't you just love incompetence?

They still are measuring the wrong endpoint! IT'S 100% RECOVERY!

• hypothermia (44 posts to February 2011)

Debate heats up following contrasting trial results on brain cooling during stroke thrombectomy

Two randomised trials presented this week at the European Stroke Organisation Conference (ESOC; 6–8 May 2026, Maastricht, Netherlands) have generated new evidence on the potential benefits of delivering intra-arterial cooling during mechanical thrombectomy procedures in large vessel occlusion (LVO) acute ischaemic stroke patients, with one producing clinical data favouring this approach and the other demonstrating safety but suggesting more neutral efficacy findings.

“The divergent results of the CHILL-ART and FOCUS trials present a classic dilemma: weighing conflicting data from similar protocols before publication,” said World Stroke Organization (WSO) vice president Gustavo Saposnik (University of Toronto, Toronto, Canada), speaking with NeuroNews in light of these first-time presentations. “While CHILL-ART suggests a robust functional benefit, FOCUS tempers this optimism, showing no functional gain despite a safety signal in reduced intracranial haemorrhage [ICH].

“This inconsistency highlights the uncertainty inherent to neurovascular research, echoing the turbulent history of [mechanical thrombectomy] prior to the 2015 pivotal trials. We must await full publication to parse technical or population differences. Currently, selective intra-arterial hypothermia remains a promise, not a proven standard. These results are hypothesis-generating; more definitive, large-scale data are required before routine integration into thrombectomy workflows.”

Positive efficacy data

CHILL-ART—the first of these multicentre randomised controlled trials (RCTs) to be shared during a late-breaking session at ESOC 2026—demonstrated that delivering targeted brain cooling during thrombectomy significantly improves recovery outcomes, as a meaningful increase in 90-day functional independence was observed in patients receiving adjunctive intra-arterial selective hypothermia versus those receiving standard thrombectomy alone.

The CHILL-ART RCT enrolled 262 anterior-circulation LVO patients across 26 comprehensive stroke centres in China. Participants aged 18–85 years and treated within 24 hours of stroke onset were randomly assigned to receive either thrombectomy plus intra-arterial infusion of cold saline in the hypothermia group, or thrombectomy with room-temperature saline in the control group.

The trial’s primary endpoint of functional independence (modified Rankin scale [mRS] score 0–2)(That's NOT 100% RECOVERY, IS IT? So failure!) at 90 days was achieved in 54.7% of patients in the hypothermia group compared to 39.8% in the control group, with an adjusted risk ratio of 1.36 (95% confidence interval [CI], 1.05–1.76; p=0.018). Investigators reported at ESOC 2026 that this equated to a number needed to treat (NNT) of seven. And, “importantly”, in the researchers’ view, safety outcomes were comparable between the hypothermia and control groups, with no significant increase in symptomatic ICH (7% vs 9%, respectively) nor 90-day mortality (13.3% vs 18%, respectively).

Subsequent sensitivity analyses also replicated these findings, indicating the robustness of the trial’s results, and outcomes were shown to be consistent across all study subgroups as well.

“Even when we successfully remove the clot, many patients do not regain independence because of ongoing brain injury after blood flow is restored,” said CHILL-ART principal investigator Zhi-Xin Huang (Southern Medical University, Guangzhou, China), who presented these data alongside Raul Nogueira (University of Pittsburgh Medical Center, Pittsburgh, USA). “Our findings show that targeted cooling delivered directly into the brain at the moment of reperfusion can meaningfully improve recovery without adding risk.”

According to the investigators, the intervention evaluated in this trial uses standard thrombectomy equipment and refrigerated saline, making it readily scalable in routine clinical practice without requiring specialised devices or additional training.

The researchers also note that, more broadly, CHILL-ART addresses a “critical unmet need” in stroke care: improving outcomes after technically successful clot removal.

By combining reperfusion with targeted neuroprotection, the study introduces a “promising new paradigm” in acute stroke treatment, and its findings may inform future clinical guidelines and support broader adoption of intra-arterial hypothermia as an accessible, cost-effective strategy to reduce disability after stroke, the investigators further posit.

Safe yet neutral outcomes

The FOCUS trial—also investigating selective intra-arterial cooling as an adjunct to thrombectomy for LVO acute ischaemic stroke, and also presented at ESOC 2026—found that, while the cooling technique did not improve functional recovery, it did significantly reduce the risk of any ICH. According to the study’s investigators, these findings therefore provide important insights into the potential role of targeted brain cooling in stroke treatment.

FOCUS was an RCT conducted across 12 hospitals in China that enrolled 258 patients with anterior-circulation LVO stroke who presented within 24 hours of symptom onset. Patients were randomly assigned to receive either selective intra-arterial cooling plus thrombectomy or standard thrombectomy treatment alone.

The trial’s results showed no significant difference in functional outcomes at 90 days between the two groups, with an adjusted common odds ratio of 1.16 (95% CI, 0.75–1.79; p=0.51). However, the cooling technique demonstrated notable safety benefits, reducing the incidence of any ICH at 24 hours compared to standard treatment (adjusted risk difference, -0.174; 95% CI, -0.288 to -0.059; p=0.003). Additionally, there was no difference in the occurrence of symptomatic ICH or mortality between groups.

The FOCUS investigators note that, while hypothermia has long been studied as a potential neuroprotective therapy for stroke based on its ability to reduce brain metabolism and limit secondary injury, its potential benefits require further study at this stage.

“These findings validate the feasibility of selective intra-arterial cooling as an adjunctive therapy during endovascular thrombectomy,” commented leading study author Shen Li (Capital Medical University, Beijing, China), who presented these data at ESOC 2026. “The marked decrease in any ICH indicates a potential protective effect on the blood-brain barrier and microvasculature, which may translate into clinical benefits. Although we did not observe a functional improvement in this trial, it paves the way for future studies with larger sample sizes or refined patient selection to fully unlock the neuroprotective potential of hypothermia.”

Life Recovery Systems secures IDE to test ThermoSuit cooling device in ischaemic stroke patients

 

All this earlier research was inconclusive. My posts on hypothermia didn't show much benefit so ask your competent? doctor why this one might have better results.

hypothermia (58 posts to February 2011)

Life Recovery Systems secures IDE to test ThermoSuit cooling device in ischaemic stroke patients

Life Recovery Systems (LRS) has received an investigational device exemption (IDE) from the US Food and Drug Administration (FDA) to test its ThermoSuit system (TSS) in a pivotal trial of ischaemic stroke patients.

The US regulator has given IDE approval for the enrolment of a maximum of 160 patients overall in up to eight hospitals. The study will randomise patients to receive standard care either with or without cooling to 32±1°C. Its primary endpoint will be post-stroke cognitive impairment, while secondary endpoints will include neurological recovery and mortality.(Why isn't the endpoint 100% recovery?  You don't believe in measuring what survivors want? That is grounds for firing!

Here is your business101 requirements. Not measuring 100% recovery is the height of incompetence!

“What's measured, improves.” So said management legend and author Peter F. Drucker )

The previous SISCO pilot clinical study—the results of which have been published in Frontiers in Neurology—concluded that the TSS was feasible to use, cooled rapidly and had acceptable safety while also showing trends suggesting improved recovery in ischaemic stroke patients.

“Laboratory studies have predicted that rapid, early cooling would be effective in reducing brain injuries caused by ischaemic strokes, while slow, delayed cooling has failed,” said Robert Schock, vice president of research and development (R&D) at LRS. “Nearly 800,000 Americans suffer strokes each year, and we believe we could help many of them.”

“This is a testament to the unmatched cooling power of the ThermoSuit system,” noted LRS chief executive officer (CEO) Matt Center. “It enhances the investment opportunity in LRS. We are looking forward to pursuing US FDA clearance for the stroke market.”

The TSS uses liquid convection cooling, typically cooling to its target temperature in 40 minutes, according to a recent press release from LRS. The release also states that core temperature is monitored while cooling and, at about 33°C, the water and patient are removed from the suit. The patient is then maintained at target for 24 hours with conventional surface cooling.

LRS further notes that this clinical trial IDE does not represent a final regulatory clearance for an ischaemic stroke indication with the TSS—and that the current US FDA-cleared indications for the device are temperature reduction where clinically indicated, such as in hyperthermic patients, and temperature monitoring.

Trust to trial brain cooling collar for head injury patients

 

All this earlier research was inconclusive. My posts on hypothermia didn't show much benefit so ask your competent? doctor if they have trialed hypothermia in their hospital and the results.

hypothermia (58 posts to February 2011)

Trust to trial brain cooling collar for head injury patients

A study will assess whether a cooling collar can improve recovery after traumatic brain injury.

The device, named CB240 Aurora, is applied around the neck and aims to lower brain temperature in a targeted way.

Brain cooling, or induced hypothermia, can limit swelling after stroke or head injury. Whole-body cooling can cause side effects such as immune suppression and chest infections.

Cambridge University Hospitals NHS Foundation Trust, which runs Addenbrooke’s Hospital, said the trial would be the “world’s first in-human study” of the device.

The collar is described as a selective temperature-control device that aims to avoid the side effects linked with whole-body cooling.

The system is portable and could be used outside hospital settings such as at roadsides or sporting events.

The trial will begin this month at Addenbrooke’s under the neurosciences and trauma critical care teams. The hospital specialises in the treatment of brain injuries and tumours.

Twenty patients with severe traumatic brain injury are expected to be enrolled over 12 months in the study, named SELETHERM 2.

Half will be randomised to receive selective brain cooling with the collar for the first 72 hours, while the remainder will receive standard current therapies.

Dr Andrea Lavinio, who is leading the study, said: “In traumatic brain injury, hypothermia has long been considered a potentially neuroprotective strategy, but large clinical trials have not demonstrated a consistent benefit.”

“One possible explanation is that the side-effects associated with whole-body cooling may outweigh any neuroprotective effects.”

“This pilot study will assess whether selective, brain-directed temperature control can be delivered while minimising systemic effects.”

Neuroprotective refers to strategies that protect brain cells from damage or death.

Dr Lavinio is a minority shareholder in Neuron Guard S.R.L, the company that developed the prototypes.

James Piercy, who suffered a severe head injury after a road accident in 2011, has advised on the study from a patient’s perspective.

He said: “I’m really excited to help the HealthTech Research Centre support technologies like this.

“Reducing the risk of the secondary injuries produced by brain swelling can dramatically improve people’s chances of a good quality of life after an accident.”

Triggered Hypothermia Protects the Brain After Injury

 Do you really think your competent? doctor and hospital can get this tested in humans? 

Triggered Hypothermia Protects the Brain After Injury

Summary: Scientists have discovered a way to induce a hibernation-like state that protects the brain after injury—without using external cooling. By activating a specific population of neurons, researchers created a reversible drop in body temperature that preserved neuron health and improved motor recovery in mice.

Brain imaging revealed reduced inflammation and greater neuron survival in damaged regions. This breakthrough could one day offer a safer, controlled method to harness hypothermia’s neuroprotective effects in treating traumatic brain injury.

Key Facts:

• Internal Hypothermia: Activating certain neurons triggered a reversible, hibernation-like state that lowered body temperature.
• Neuroprotection: Mice treated this way showed better motor performance and neuron survival after brain injury.
• Reduced Inflammation: Brain imaging revealed less neuroinflammation in injured tissue compared to controls.

Source: SfN

Hypothermia can preserve neuron health following brain injury, but complications from external cooling make it less promising therapeutically.

Recent evidence suggests that activating a specific neuron population triggers a reversible, hibernation-like hypothermic state without external cooling, but does this form of hypothermia still preserve neuron health?

In a new Journal of Neuroscience paper, researchers led by Takeshi Sakurai at the University of Tsukuba explored this question using male mice. 

The researchers found that triggering this specific hypothermic state in mice improved motor performance following brain injury. Imaging methods showed that neurons also had improved survival in the injured brain area accompanied by less signs of neuroinflammation.

The researchers further identified cellular features consistent with the idea that this form of hypothermia may preserve neural health. 

While this work is preclinical, the authors suggest that it unveils a potential way to work around complications from external cooling when using hypothermia as a treatment for traumatic brain injury.

Speaking on future experimental plans, says Sakurai, “Optimizing the timing and duration of this treatment after injury, testing across additional injury models, and evaluating safety and efficacy in larger animals will be important next steps.”

Key Questions Answered:

Q: What is hypothermia therapy for brain injury?

A: Hypothermia therapy lowers body temperature to slow cellular damage and inflammation after injury, preserving neuron health.

Q: What makes this approach different?

A: Instead of using external cooling, researchers triggered a natural, neuron-driven hypothermic state similar to hibernation.

Q: Why does this matter for future treatments?

A: It could help develop safer, more precise hypothermia-based therapies without complications linked to external cooling.

About this neurology research news

Author: SfN Media
Source: SfN
Contact: SfN Media – SfN
Image: The image is credited to Neuroscience News

Innovation using hypothermia for stroke treatment

 Can't figure out what drug they are talking about, so ask your competent? doctor for details and when research is complete and when the protocol will get to their hospital.

All this earlier research was inconclusive. My posts on hypothermia didn't show much benefit so I don't know where she's seeing that.

hypothermia (56 posts to February 2011)

 

Innovation using hypothermia for stroke treatment

The effect of inadvertent systemic hypothermia after mechanical thrombectomy in patients with large-vessel occlusion stroke

 What created protocol is your competent? hospital following in this until further research is done? Do they even have ANY PROTOCOLS FOR STROKE?

The effect of inadvertent systemic hypothermia after mechanical thrombectomy in patients with large-vessel occlusion stroke

Kristina auf dem Brinke¹Fabian Kück²Ala Jamous³Marielle Ernst³Nils Kunze-Szikszay⁴Marios-Nikos Psychogios⁵Ilko L. Maier^1*

• ¹Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
• ²Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany
• ³Department of Neuroradiology, University Medical Center Göttingen, Göttingen, Germany
• ⁴Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany
• ⁵Department of Neuroradiology, Universitätsspital Basel, Basel, Switzerland

Background and aims: Postinterventional hypothermia is a frequent complication in patients with large-vessel occlusion strokes (LVOS) after mechanical thrombectomy (MT). This inadvertent hypothermia might potentially have neuroprotective but also adverse effects on patients’ outcomes. The aim of the study was to determine the rate of hypothermia in patients with LVOS receiving MT and its influence on functional outcome.

Methods: We performed a monocentric, retrospective study using a prospectively derived databank, including all LVOS patients receiving MT between 2015 and 2021. Predictive values of postinterventional body temperature and body temperature categories (hyperthermia (≥38°C), normothermia (35°C–37.9°C), and hypothermia (<35°C)) on functional outcome were analyzed using multivariable Bayesian logistic regression models. Favorable outcome was defined as modified Rankin Scale (mRS) ≤3.

Results: Of the 480 included LVOS patients with MT (46.0% men; mean ± SD age 73 ± 12.9 years), 5 (1.0%) were hyperthermic, 382 (79.6%) normothermic, and 93 (19.4%) hypothermic. Postinterventional hypothermia was significantly associated with unfavorable functional outcome (mRS > 3) after 90 days (OR 2.06, 95% CI 1.01–4.18, p = 0.045). For short-term functional outcome, patients with hypothermia had a higher discharge NIHSS (OR 1.38, 95% CI 1.06 to 1.79, p = 0.015) and a higher change of NIHSS from admission to discharge (OR 1.35, 95% CI 1.03 to 1.76, p = 0.029).

Conclusion: Approximately a fifth of LVOS patients in this cohort were hypothermic after MT. Hypothermia was an independent predictor of unfavorable functional outcomes. Our findings warrant a prospective trial(WHO EXACTLY ARE YOU CONTACTING TO GET THIS FURTHER RESEARCH DONE? NOBODY? So you're incompetent?) investigating active warming during MT.

Therapeutic hypothermia for stroke: Unique challenges at the bedside

 All this earlier research was inconclusive so why this repeat research rather than do some actual research that might get it successfully translated to clinical interventions?  I blame the mentors and senior researchers for the failure of setting correct objectives. The whole point of stroke research is to solve stroke, not just tell us of the problems that exist in solving stroke. LEADERS SOLVE PROBLEMS; Are you a leader or a mouse?

• hypothermia (54 posts to February 2011)

 

Therapeutic hypothermia for stroke: Unique challenges at the bedside

Je Sung You^1†, Jong Youl Kim^2† and Midori A. Yenari^3*

• ¹Department of Emergency Medicine, Yonsei University College of Medicine, Seoul, South Korea
• ²Department of Anatomy, Yonsei University College of Medicine, Seoul, South Korea
• ³Department of Neurology, The San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA, United States

Therapeutic hypothermia has shown promise as a means to improving neurological outcomes at several neurological conditions. At the clinical level, it has been shown to improve outcomes in comatose survivors of cardiac arrest and in neonatal hypoxic ischemic encephalopathy, but has yet to be convincingly demonstrated in stroke. While numerous preclinical studies have shown benefit in stroke models, translating this to the clinical level has proven challenging. Major obstacles include cooling patients with typical stroke who are awake and breathing spontaneously but often have significant comorbidities. Solutions around these problems include selective brain cooling and cooling to lesser depths or avoiding hyperthermia. This review will cover the mechanisms of protection by therapeutic hypothermia, as well as recent progress made in selective brain cooling and the neuroprotective effects of only slightly lowering brain temperature. Therapeutic hypothermia for stroke has been shown to be feasible, but has yet to be definitively proven effective. There is clearly much work to be undertaken in this area.(But you did NOTHING TO SOLVE THAT PROBLEM!)

Introduction

Acute ischemic stroke is the primary cause of about 85% of strokes worldwide and is most frequently caused by blood clots or atherosclerosis occluding cerebral blood flow (1, 2). Studies have shown that decreasing the time between presentation and intervention can improve clinical outcomes (2, 3). Modern management efforts thus emphasize the time sensitivity of stroke treatment. Antiplatelet and anticoagulant drugs have long been the mainstay of ischemic stroke management, along with the use of acute thrombolysis and mechanical thrombectomy to revascularize thrombosed vessels (4–6). If initiated rapidly, these revascularization strategies reduce morbidity and improve neurological outcomes, although the window for these interventions is on the order of hours (6, 7). Unfortunately, due to a variety of constraints, a majority of patients tend to present too late for these interventions and are not eligible for potentially life-saving and disability-preventing treatments (8–11). Thus, adjunctive treatments may be needed to extend this critical time interval to offer treatments to a broader number of stroke victims.

Therapeutic hypothermia (TH) has been suggested as a potential approach to achieve the goal (12, 13). In 2002, two randomized controlled trials (RCT) showed the induction of mild hypothermia (32–34°C) produced more favorable neurologic outcomes and improved survival after cardiac arrest compared with patients for whom body temperatures were maintained in the normothermic range (14, 15). TH has since been rapidly implemented worldwide and established as a gold standard in the management of comatose survivors of cardiac arrest; however, TH has only been shown to be effective at the clinical level in patients suffering from cardiac arrest and in neonates suffering from hypoxic ischemic encephalopathy (HIE) (16–18). In this review, TH refers to cooling the body in order to preserve organ viability and is so far the most effective therapy for improving neurological outcomes in comatose survivors of cardiac arrest (14, 18, 19). Subsequent studies have also shown that modulation of body temperature to normal and slightly below normal levels may also be beneficial. Thus, the term targeted temperature management (TTM) refers to modulation of body temperature including TH.

In spite of the optimism of TTM in cardiac arrest and neonatal HIE, clinical applications of TTM in other acute brain injuries, such as hemorrhagic or ischemic stroke and traumatic brain injury, have yet to demonstrate improvement in clinical outcomes (20–25). Yet, multiple preclinical studies have consistently shown that TH induces multiple and synergistic effects for neuroprotection in experimental models (16, 26). A major challenge in translating this to the clinical level is that therapeutic hypothermia studies in many experimental models used small species where whole body cooling can be achieved in a short period of time. By contrast, humans have much larger mass, and whole body cooling to achieve target brain temperatures for optimal neuroprotection requires many hours. Furthermore, patients with stroke are typically older with comorbidities, which could complicate TH. Thus, selectively cooling the brain has the potential not only to achieve more rapid cooling but may reduce systemic complications. Efforts to achieve this included using internal catheters to reduce temperatures of the cerebral vessels, which would then cool brain tissue (23, 25), or cooling caps to directly cool the brain (27–29), but these approaches have achieved limited success. Regardless, it is clear that reducing brain temperature can improve neurological outcomes from many acute brain insults. This review covers the current state of TTM as it relates to clinical stroke care.

Mechanisms of hypothermic protection in experimental ischemic stroke

To understand the robust neuroprotective effects of TH, it is important to understand the preclinical works related to understanding why TH seems so effective. TH has long been thought to lead to beneficial effects by decreasing brain metabolism (16), but through multiple experimental studies, it has now been recognized that TH exerts neuroprotection by favorably altering a broad range of pathological pathways, including the regulation of brain metabolism, apoptosis, microglial activation, cerebral blood flow, inflammation, and neurotrophic factors (16, 26). As such, this may be a major reason why lowering brain temperature may lead to preservation of brain tissue and function.

Effect of hypothermia on brain metabolism, blood flow, and excitotoxicity

In ischemic stroke models, hypothermia to brain at temperatures of 33°C (mild hypothermia) showed improved cerebral blood flow and preservation of the cellular metabolic rate (30, 31). During stroke, cerebral blood flow (CBF) is disrupted following vessel occlusion. If blood flow is restored (reperfusion), there is a brief and abrupt overshoot of CBF, followed by gradual deterioration. Microvascular narrowing was thought to underlie this deterioration (32), and TH has been shown not only to improve and maintain CBF by preventing microcirculatory collapse but also seems to prevent this brief overshoot of CBF upon reperfusion (33).

Brain metabolism is also sensitive to temperature. Mild hypothermia reduces oxygen consumption by a ~5%/°C decrease in body temperature in the range of 22–37°C (2). Cerebral ischemia also leads to increased accumulation of extracellular glutamate and influx of calcium (34). Hypothermia has been documented to prevent glutamate accumulation and subsequent excitotoxicity mediated by calcium influx (26, 35). More recently, hypothermia also appears to suppress the calcium-sensing receptor (CaSR) expression, which regulates calcium influx and upregulates the inhibitory gamma-aminobutyric acid B receptor 1 (GABA-B-R1) (36). As such, hypothermia appears to induce neuroprotective effects in ischemia models by affecting multiple aspects of brain metabolism and neurotransmission.

Neuroprotection by hypothermia: Cell death pathways

Beyond early observations that hypothermia preserves tissue metabolic reserves and reduces ischemic elaboration of excitotoxins, hypothermia has also been shown to positively influence several ischemic cell death pathways, such as apoptosis (37). Several studies have shown that hypothermia can prevent apoptotic cell death in stroke models (38–40). TH was first shown to affect several aspects of the intrinsic pathway, ultimately leading to neuroprotection. The intrinsic pathway is initiated within the cell mitochondria via release of various factors, such as cytochrome c and apoptosis-initiating factor (AIF), into the cytosol (41). Mild hypothermia has been shown to increase the anti-apoptotic protein Bcl-2, which, in turn, inhibits cytosolic cytochrome c release and subsequent caspase activation (42). A few studies have also shown that mild hypothermia reduces the generation of pro-apoptotic Bax (43–46). Downstream of Bcl2, hypothermia has been shown to influence protein kinase C (PKC) family members, such as anti-apoptotic (PKCε) or pro-apoptotic (PKCδ), so as to lead to overreduction in apoptotic cell death (39).

The extrinsic apoptotic pathway is triggered via death receptors, which, when ligated, leads to cell death. A prototypical death receptor, Fas, and its corresponding ligand, Fas ligand (FasL), have also been studied in stroke models, and interrupting this pathway has been shown to improve outcomes in stroke models (47). TH has been shown to decrease the expression of Fas and FasL and subsequent activation of downstream caspase-8 (48–51).

TH can also affect caspase-independent apoptosis. The mitochondrial apoptosis-inducing factor (AIF) pathway involves direct apoptotic cell death and is capable of inducing apoptosis without activating caspases (52). Mild hypothermia suppressed AIF translocation from the mitochondria to the cytosol and led to reduced apoptotic cell death in an ischemic stroke model (53). In sum, TH is capable of influencing many cell death pathways in such a way so as to favor cell survival.

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