Year: 2026
Type: editorial
Abstract: Stroke remains among the leading causes of death and acquired disability worldwide, and the therapeutic advances of recent decades have expanded the range of problems that contemporary stroke management must address. Reperfusion therapy has been extended to later time windows and to larger ischaemic cores, case fatality has fallen across many health systems, and a growing population of survivors consequently live for years with cognitive, affective and physical sequelae. The clinical problem has therefore shifted, at least in part, from improving survival towards characterising the aftermath of acute stroke.The first volume of this Research Topic addressed acute biomarkers, neuromodulation and rehabilitation technology. The present volume comprises eighteen contributions, and its most striking feature is the breadth of disciplines from which they have emerged, appearing across eight Frontiers journals encompassing neurology, human neuroscience, psychiatry, neuroscience, surgery, pharmacology, endocrinology and nutrition; with the strongest submissions concerning inflammation, immune competence, metabolism, mood, cognition, surgical judgement and cost, frequently within the same patient.Four contributions address the first hours and days after onset, each engaging a decision for which trial evidence remains incompletely defined.United States comprehensive stroke centre, comparing thirty-two treated patients with a historical standard-care cohort. No symptomatic or asymptomatic intracranial haemorrhage occurred by any of three standard definitions, and no thrombocytopenia was observed.Importantly, and in contrast to the trial on which the protocol was based, more than eighty per cent received tirofiban after early neurological deterioration had already occurred, at a median of 28.8 h from last known well. The authors therefore describe a rescue strategy for a population in whom current guidelines recommend no targeted therapy, and appropriately characterise their favourable neurological outcomes as hypothesis-generating. Xie L. et al. analysed 48,294 Xie F. et al. contribute a health-economic dimension too infrequently addressed in acute stroke research, modelling edaravone dexborneol administered as a sublingual tablet versus concentrated solution for injection. Using clinical inputs from the TASTE-SL and TASTE trials, the proportion achieving a modified Rankin Scale score of ≤1 did not differ significantly between formulations, while the oral formulation outperformed in costeffectiveness. The more consequential implication may be one of accessibility, since an oral route removes the infusion infrastructure otherwise required. Lin et al. prospectively sampled peripheral blood on days 1, 3 and 7 following endovascular therapy in acute anterior circulation large vessel occlusion, measuring monocyte human leukocyte antigen-DR (mHLA-DR) expression alongside interleukin-6, C-reactive protein and procalcitonin. Following multivariate adjustment, it was reduced mHLA-DR expression at day 1, together with dysphagia, that independently predicted stroke-associated pneumonia.As mHLA-DR is an established marker of monocyte activity and plays a central role in the immune response, this finding implicates stroke-induced immunodepression rather than excess inflammation. These findings complement the registry data of Xie L. et al., in which pneumonia affected more than a quarter of thrombolysed patients with atrial fibrillation. These immunological findings suggest both a possible mechanism and a way of identifying susceptible patients early Complications are not exclusively immune-mediated, however, and Zhang W. et al. address one that is largely iatrogenic and, in principle, preventable. In 305 patients with severe stroke, refeeding syndrome following initiation of enteral nutrition was accompanied by the characteristic fall in serum phosphorus and was associated with significantly higher rates of new acute liver injury, acute kidney injury, mechanical ventilation and 28-day mortality, together with worse modified Rankin Scale scores at discharge. The main implication is therefore one of prevention rather than prediction, and nutritional management in severe stroke may deserve more attention than it currently receives.Six contributions address depression after stroke, the largest cluster in this collection and, given that the condition affects approximately one third of survivors and remains underrecognised, this represents a much welcomed emphasis.Four pursue a common strategy, namely the identification of at-risk patients using laboratory values obtained at admission. Su et al. prospectively followed 318 patients with first-ever acute ischaemic stroke, finding that those in the highest tertile of the systemic immuneinflammation index were 3.5 times more likely to develop depression at three months. In two complementary analyses of a single cohort at Shanxi Bethune Hospital, Kong et al. (2025) examined the admission uric acid to high-density lipoprotein cholesterol ratio and Kong et al.(2026) the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio, reporting independent associations with 90-day depressive outcomes in both instances; in the latter, each unit increase conferred approximately 35% higher odds following adjustment.Luo et al. extended this approach to haemorrhagic stroke, demonstrating in 446 patients with spontaneous intracerebral haemorrhage that admission serum prealbumin was lower among those subsequently diagnosed with depression. Given that prealbumin is a negative acutephase protein, the direction of this association is concordant with the inflammatory findings in the previous contributions discussed.The practical appeal is worth noting, in that risk stratification may require no new assays but better use of measurements already present in the medical record. The predictive performance of any single index nonetheless remains modest, and the next step is to compare these markers directly and to test them prospectively, for which these studies provide a useful foundation.Two reviews supply the mechanistic account that renders such associations biologically plausible. Tang et al. review impaired hippocampal neurogenesis as a mechanism of poststroke depression. Ischaemic injury does increase neural stem cell proliferation acutely, yet the hippocampus derives little benefit: proliferation is short-lived, few progenitors survive, cell fate shifts towards astrogenesis, and the neurons produced are often abnormal in shape and location. The authors also review hypothalamic-pituitary-adrenal axis hyperactivity, neuroinflammation, reduced brain-derived neurotrophic factor signalling and monoaminergic disturbance. One pathway is of particular interest here: interleukin-6 drives indoleamine 2,3dioxygenase, which diverts tryptophan away from serotonin synthesis. This is precisely the biology that would link a raised inflammatory index at admission to depression months later.Li and Gao review depression following intracerebral haemorrhage, reported between 18% and 60% and less well characterised than its ischaemic counterpart. Alongside monoamine imbalance and bidirectional neuroinflammation, they emphasise oxidative stress and iron dysregulation arising from the breakdown of extravasated blood, mechanisms that are specific to haemorrhage and that argue against simply applying frameworks developed for ischaemic stroke. points on the Fugl-Meyer Assessment for the Upper Extremity was achieved by 91.7% of the intervention group compared with 43.3% of controls, with corresponding gains reflected in the Barthel Index and Functional Independence Measure. Given that upper limb recovery remains one of the most difficult problems in stroke rehabilitation, and that the subacute window represents the period of greatest neuroplastic capacity, trials of this kind therefore address an important gap.Taken together, these eighteen contributions describe a field in which progress is occurring across several distinct areas. The most consistent theme across the collection is the effort to extract prognostic information from data that already exist, whether admission blood results, registry records or routine bedside assessment. Such approaches are widely applicable, and are of particular relevance to centres without access to advanced imaging or specialised biomarker panels. Low-cost prognostic information is essential if risk stratification is to be feasible at scale, and several studies collected here represent progress towards that objective.
Source: Frontiers in Human Neuroscience
Authors: William Huynh, Nasser Kashou
Institutions: The University of Sydney, UNSW Sydney
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223304000