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After a stroke, the brain runs a repair programme of its own. The microglia, the brain’s resident immune cells, switch out of their initial inflammatory state and into a reparative one, producing growth factors such as insulin-like growth factor 1 (IGF1) that rebuild myelin around damaged nerve fibres and strengthen synaptic connections. This is a large part of what makes the early months after stroke so productive for rehabilitation… but it only lasts around two months, and once it fades, deficits tend to become permanent. Why it fades has never been well understood…

A team at the Institute of Science Tokyo, working with the Tokyo Metropolitan Institute of Medical Science, Kyushu University and the University of Freiburg, published their findings in Nature on 13 May 2026. They identified a transcription factor called ZFP384 which rises as the microglia lose their reparative properties; it disrupts the chromatin interactions mediated by a protein called YY1 that the microglia need in order to express their repair genes. The point with ZFP384, is that as it climbs, the repair programme switches off regardless of whether the brain still needs it. When the team deleted the Zfp384 gene from microglia in mouse stroke models, those animals held onto their recovery-associated gene expression far longer, with better remyelination, more synaptic plasticity and improved long-term neurological function.

They then built a therapeutic antisense oligonucleotide, ASO-Zfp384, to suppress the gene directly. An ASO is a short synthetic strand of nucleic acid designed to bind to the messenger RNA of a specific gene and trigger its degradation, turning that gene’s expression down. Six ASOs already hold FDA approval across three neurological conditions, including nusinersen for spinal muscular atrophy and tofersen for SOD1-associated ALS. ASOs cannot cross the blood-brain barrier when given systemically, so they are delivered by intrathecal injection into the cerebrospinal fluid, spreading along the neuraxis into the spinal cord and brain; imaging studies show glial cells take them up before neurons do, which matters here, since microglia are the target.

The timing of the ASO-Zfp384 results is significant…  the treatment sustained microglial reparative function and still worked when given a week, and even a month, after stroke onset; far outside the window in which clot-busting drugs are useful. Rather than suppressing inflammation, which has been the conventional approach, it retained the brain’s own repair programme. The team then examined brain tissue from human stroke patients and found the same relationship: as the human equivalent, ZNF384, rose, IGF1 declined. This is obviously animal research and the distance to the clinic is considerable; the next stage is safety and efficacy testing in larger preclinical models before any move toward human trials, so realistic NHS availability is a decade or more away. But. very interesting data to absorb.

If you’ve come across transcranial magnetic stimulation (rTMS) as a possible (clinical) add-on to stroke rehabilitation, an interesting review published in July 2026 in the journal Brain Sciences, led by Marcin Karol Setlak and colleagues at the Medical University of Silesia in Poland, draws a careful line between what the tech can and cannot yet do. rTMS is a non-invasive way of changing the excitability of the brain’s motor and language networks; the idea is not to replace rehabilitation but to prime the affected area so that the physiotherapy or speech work you do afterwards lands more effectively. The review’s focus is a more precise version of it; neuronavigated rTMS (nrTMS)… which links the stimulation to your own MRI scan and tracks the coil position in real time.

So, conventional rTMS is usually aimed using scalp landmarks or standard coordinate systems, which give only a rough approximation of the cortical target underneath… and after a stroke, the lesion, the surrounding reorganisation and any change in brain shape can shift the relationship between the scalp and the region you want to stimulate. So two patients treated on the same nominal protocol can end up with stimulation over different targets. Neuronavigation reduces that uncertainty; the target is defined on the patient’s own MRI, the coil position and angle are monitored during stimulation, and the same target can be reproduced session after session. When rTMS is delivered over many sessions alongside motor training, that reproducibility matters, because small differences in coil placement otherwise add up.

Stroke is the most studied use of rTMS in rehabilitation, mostly for upper-limb motor recovery, but also for aphasia, neglect and dysphagia. Two broad strategies are common; low-frequency stimulation (around 1 Hz) to the undamaged hemisphere to reduce its inhibitory influence, or high-frequency stimulation to the damaged hemisphere to boost its activity. Both rest on the interhemispheric imbalance model, but the review is clear that neither should be applied mechanically… in patients with extensive damage to the corticospinal tract, boosting the lesioned side may not be enough, and in patients who rely on the other hemisphere for residual movement, suppressing it may do harm. Which strategy suits you depends on your lesion, your remaining motor output, and how far your networks have already reorganised.

Better targeting is not the same as better outcomes, and the review is direct about the difference. Neuronavigation improves the accuracy and reproducibility of where the coil sits, but it does not by itself control how far the stimulation spreads through the tissue, which depends on coil design, coil-to-cortex distance, intensity and your individual anatomy. And most of the clinical evidence supporting rTMS after stroke was gathered using conventional, non-navigated protocols. So its specific superiority over standard rTMS in stroke recovery has not yet been shown in controlled trials.

The authors call nrTMS a precision-enhancing tool rather than a treatment in its own right. rTMS in general is available in some UK centres for selected uses, but neuronavigated protocols for stroke rehabilitation remain specialised and investigational, held back by equipment cost, the need for recent MRI, planning time, operator training, and close teamwork between neurologists, physiotherapists and neurophysiology teams. Routine NHS use for stroke is some way off and depends on trials showing the added precision produces real functional gains. At ARNI, the ARNI Instructors and I work on the principle that any priming intervention only counts if the rehabilitation that follows is intensive and task-specific; nrTMS is worth following, but the training that comes after it is still what does the work.

Did you know that strokes follow predictable time-of-day patterns? They happen more often in the morning hours and are often more severe near the end of the sleep period. A study published in the Journal of Clinical Investigation, led by Lauren Hablitz PhD at the University of Rochester Medicine and building on more than a decade of research by Maiken Nedergaard MD DMSc (whose lab discovered the glymphatic system in 2012), found that reinforcing the body’s natural daily rhythms after stroke improved motor recovery, shrank lesion size, lowered brain inflammation and boosted the brain’s waste-clearing system in mouse models. The benefits appeared even when treatment started three days after the stroke, well beyond the window for clot-busting drugs.

The glymphatic system circulates cerebrospinal fluid through brain tissue, clearing waste products and the inflammatory signals that build up after injury. This clearance is most active during sleep and controlled by the body’s internal 24-hour clock; stroke disrupts both, which slows the cleaning down when the brain needs it most. As Hablitz puts it: ‘stroke is not just a vascular event, but a disorder of timing.’ Her theory is that much of the lingering damage after stroke comes down to a failure of clearance: ‘if the system responsible for clearing signalling molecules isn’t working properly, everything builds up.’

The researchers tested four ways of restoring circadian rhythm: timed light exposure, melatonin, a clock-targeting drug called KL001, and time-restricted feeding (eating within a set daily window). KL001 and time-restricted feeding were then tested in stroke models, and both improved recovery, reduced lesion size and lowered inflammation. ‘All of the cytokines moved in the same direction,’ Hablitz notes… the brain appeared to be clearing inflammatory signals across the board rather than the treatment hitting one single target. Time-restricted feeding is already under study for heart disease and diabetes; it needs no specialist equipment and could, in principle, be done at home.

This is still animal research and human trials are needed before anyone can say it works the same way in people. Hablitz’s next steps are to establish whether improved glymphatic flow directly drives recovery and whether circadian-based interventions can move into clinical trials. At ARNI, the ARNI Instructors and I treat sleep and daily rhythm as rehabilitation factors rather than background lifestyle advice; this research sets out a neurological mechanism behind that.

If you have had a lacunar stroke, you probably have been told it was caused by fatty plaque narrowing your arteries, and put on aspirin or another antiplatelet drug to prevent the next one. New research from the University of Edinburgh, published in the journal Circulation in July 2026, suggests that picture may be wrong; the strongest link was not with narrowed arteries at all, but with the widening and enlargement of the small blood vessels deep within the brain. This helps explain why the standard drugs you may be taking have often had limited success at preventing this particular kind of stroke.

Lacunar stroke happens when the brain’s tiniest blood vessels are damaged by a condition called small vessel disease. It is a major cause of disability and is linked to cognitive decline, dementia and a raised risk of further strokes; but until now, no one has been able to pin down exactly what drives it, which of course has made it hard to treat properly. To investigate, researchers from the University of Edinburgh, the UK Dementia Research Institute and international collaborators studied 229 people who had had either a lacunar stroke or a mild non-lacunar stroke. Each had clinical and cognitive assessments and MRI brain scans shortly after their stroke and again a year later, so the team could track the type of stroke, monitor the small vessel disease, and spot any new brain damage that developed over the year.

The results turned the usual assumption on its head. Narrowing of the larger arteries was not associated with lacunar stroke or with small vessel disease at all; it was more common in other forms of stroke, but it did not predict new brain damage on the follow-up scans. Artery widening was the opposite story. Patients with enlarged, widened arteries were more than four times more likely to have had a lacunar stroke… and the widening was also linked to more severe small vessel disease, faster progression of brain damage, and a greater chance of developing new ‘silent’ strokes… small areas of brain injury that happen without obvious symptoms. More than one in four participants developed these silent strokes during the study, even though they were taking the standard treatments meant to prevent them.

As Joanna Wardlaw, Professor of Applied Neuroimaging at the University of Edinburgh, puts it: ‘this study provides strong evidence that lacunar stroke is not caused by fatty blockage of larger arteries, but by disease of the small vessels within the brain itself… it explains why conventional treatments like antiplatelet drugs are not as effective for this type of stroke and highlights the urgent need to develop new therapies that target the underlying microvascular damage’. The point is not that aspirin is useless, but that for lacunar stroke it may have been aimed at the wrong target all along.

The research is already feeding into new treatment strategies. The LACunar Intervention Trial 3 (LACI-3) is testing whether existing medicines, including cilostazol and isosorbide mononitrate, can protect the brain’s small vessels, lower the risk of further strokes, and reduce long-term problems with memory, mobility and dementia after lacunar stroke. These drugs are already licensed for other uses, which could shorten the path to routine prescription if the trials succeed; but LACI-3 needs to report and be reviewed before anything changes in standard care, so realistic NHS use for lacunar stroke is still a few years away.

I’ve detailed Neubond on this Blog before – good news.. it’s on its way! As you know so well, after stroke, trying to move your affected hand and feeling nothing happen is one of the most frustrating experiences you can have… ut because the link between the brain’s intention to move and the sensory feedback that confirms movement has broken down.

Neubond, an Imperial College London spinout founded by Dr Patrick Sagastegui Alva, Jumpei Kashiwakura and Professor Dario Farina (head of Imperial’s Neuromechanics and Rehabilitation Technology lab, whose team spent over a decade developing the core science), has just announced a £1.5 million seed funding round led by Waseda University Ventures (its first investment in a UK company), alongside SFC Capital and New Wave Ventures, to finalise its wearable stroke rehabilitation platform and complete a pivotal clinical study at Charing Cross Hospital.

The device is basically a compact bracelet worn on the forearm. Sensors inside detect faint electrical signals from muscles even when the patient cannot see or feel any movement occurring; when the bracelet picks up a signal, a companion app shows the patient in real time that their muscle has activated, closing the sensory feedback loop that stroke has opened. As Professor Farina puts it: ‘we have strong evidence that neuroplasticity can be induced by detecting a motor command and applying artificial sensory feedback… guiding the brain to remake connections.’ The tech originated from prosthetic hand interface research; Sagastegui and Kashiwakura realised the detection component had an independent clinical application for stroke rehabilitation and built from there.

In a pilot with 15 patients, range of motion improved by 30% after one month. These are early numbers from a small sample; the Charing Cross study will provide the larger dataset needed to inform a full clinical trial and MHRA approval. The funding also completes product development toward a device that can be used at home independently and monitored remotely by clinicians… which addresses one of the most persistent gaps in stroke rehab: what continues (or more commonly does not continue) after hospital discharge. Co-founder Kashiwakura is direct about the aim: ‘motivation is vital for stroke patients; our platform uses a simple biofeedback mechanism so that patients can see the effect their rehabilitation efforts are having.’

Neubond is of course not yet available and MHRA approval is still ahead; routine availability is realistically several years away.

BOTOX never did much for your spasticity? Or never worked as well as you hoped? Now there is a longer-lasting NHS-available alternative that a number of ARNI survivors have tried and rated positively. Cryoneurolysis has been used in medicine since the 1970s for sensory pain management; in 2018 researchers adapted it to target the motor nerves driving spasticity specifically, and by January 2024 Oxford University Hospitals NHS Foundation Trust had established a routine cryoneurolysis service at the Oxford Centre for Enablement, accepting GP and consultant referrals from anywhere in the UK. Botulinum toxin has a dose ceiling, a duration limit of around 3 months, and can develop tachyphylaxis, diminishing response with repeated injections over time; cryoneurolysis has none of those constraints, and its duration of effect of 6 to 12 months from a single treatment is one of its most practical advantages.

The procedure uses a handheld probe to freeze targeted nerve fibres to around -88°C, temporarily halting the signals driving spasticity while leaving the endoneurium, the nerve’s structure, intact; natural regeneration follows over 6 to 9 months. A diagnostic nerve block with local anaesthetic is performed first; if your muscle relaxes and passive mobility improves, you’re confirmed as a candidate, and the cryoprobe is then guided to the precise motor nerve using ultrasound and electrical stimulation so surrounding tissue is unaffected.

The positive evidence for the intervention seems to building quite consistently, but is still primarily case series rather than large-scale RCTs. For example, a feasibility case series published in Neurology International in April 2026, treating three adults with chronic post-stroke hemiparesis, found MAS scores decreased by at least 2 points in targeted patterns with improvements sustained at 6 months and no serious adverse events. A larger 2025 study of 59 participants with plateaued or refractory upper limb spasticity found significant improvements at 12 months in shoulder abduction (+9.7°), shoulder flexion (+8.1°) and elbow extension (+21.3°), alongside MAS reductions of 2.0 points for shoulder abduction and 1.7 for shoulder flexion… average daily pain, participant satisfaction and upper limb disability all improved. A January 2026 case in Neurology International documented a stroke survivor 12 years post-injury with an implanted FES device; targeted sequential cryoneurolysis improved his gait deviation index beyond minimal detectable difference thresholds – confirming for the first time that cryoneurolysis is fully compatible with implanted FES devices.

In Luxembourg, the spastiCRYO-LL trial received ethics committee approval in April 2024 and is generating the first quantitative gait-laboratory evidence for cryoneurolysis at scale. In Canada, a mechanistic pilot study at Parkwood Institute is targeting 25 stroke patients to characterise neuroplasticity effects via TMS, fMRI and near-infrared spectroscopy – testing whether the controlled nerve disruption cryoneurolysis creates may itself trigger neuroplastic reorganisation beyond simple tone reduction. In the UK it’s available at Oxford University Hospitals, the National Hospital for Neurology and Neurosurgery at Queen Square (UCLH) and St George’s University Hospitals. Your GP, stroke physician or neurologist must submit a formal referral.