Long-term Stroke Recovery Research Articles

Peripheral, but not central, IGF-1 treatment attenuates stroke-induced cognitive impairment in middle-aged female Sprague Dawley rats: The gut as a therapeutic target

Stroke results in immediate sensory or motor disability and increases the risk for long term cognitive-affective impairments. Thus, therapies are urgently needed to improve quality of life for stroke survivors, especially women who are at a greater risk for severe stroke after menopause. Most current research on stroke therapies target the central nervous system; however, stroke also impacts peripheral organ systems. Our studies using acyclic (estrogen-deficient) middle aged female Sprague Dawley rats show that this group not only displays worse outcomes after stroke as compared to adult females, but also has lower levels of the neuroprotective peptide Insulin-like Growth Factor (IGF1) in circulation. Intracerebroventricular (ICV) administration of IGF1 to this group decreases infarct volume and improves sensory motor performance in the acute phase. In this study, we show that, despite this neuroprotection, ICV-IGF1 did not reduce peripheral inflammation or improve post stroke cognitive impairment in the chronic phase. In view of the evidence that stroke induces rapid gut dysfunction, we tested whether systemic delivery of IGF1 (intraperitoneal, IP) would promote gut health and consequently improve long-term behavioral outcomes. Surprisingly, while IP-IGF1, delivered 4 h and 24 h after ischemic stroke, did not reduce infarct volume or acute sensory motor impairment, it significantly attenuated circulating levels of pro-inflammatory cytokines, and attenuated stroke-induced cognitive impairment. In addition, IP-IGF1 treatment reduced gut dysmorphology and gut dysbiosis. Our data support the conclusion that therapeutics targeting peripheral targets are critical for long-term stroke recovery, and that gut repair is a novel therapeutic target to improve brain health in aging females.

Combination of Atractylenolide I, Atractylenolide III, and Paeoniflorin promotes angiogenesis and improves neurological recovery in a mouse model of ischemic Stroke

BackgroundPrognosis is critically important in stroke cases, with angiogenesis playing a key role in determining outcomes. This study aimed to investigate the potential protective effects of Atractylenolide I (Atr I), Atractylenolide III (Atr III), and Paeoniflorin (Pae) in promoting angiogenesis following cerebral ischemia.MethodsThe bEnd.3 cell line was used to evaluate the effects of these three compounds on vascular endothelial cell proliferation, migration, and tube formation. Male C57BL/6 mice underwent transient middle cerebral artery occlusion (MCAO), followed by daily intragastric administration of the Chinese medicine compounds to assess their impact on brain protection and angiogenesis. In vivo experiments included measuring infarct size and assessing neurological function. Immunofluorescence staining and an angiogenesis antibody array were used to evaluate angiogenesis in ischemic brain tissue. Functional enrichment analysis was performed to further investigate the pathways involved in the protective effects of the compounds. Molecular docking analysis explored the potential binding affinity of the compounds to insulin-like growth factor 2 (IGF-2), and Western blotting was used to measure levels of angiogenesis-related proteins.ResultsIn vitro, the combination of Atr I, Atr III, and Pae enhanced cell proliferation, promoted migration, and stimulated tube formation. In vivo, the combined treatment significantly facilitated neurological function recovery and angiogenesis by day 14. The treatment also increased levels of angiogenesis-related proteins, including IGF-2. Pearson correlation analysis revealed a strong positive association between IGF-2 levels in ischemic brain tissue and angiogenesis, suggesting a good affinity of the compounds for the IGF-2 binding site, as supported by molecular docking analysis.ConclusionThe administration of Atr I, Atr III, and Pae has shown significant enhancements in long-term stroke recovery in mice, likely due to the promotion of angiogenesis via increased activation of the IGF-2 pathway in ischemic brain tissue.Graphical

Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhages

BackgroundThe intravenous delivery of adult neural precursor cells (NPC) has shown promising results in enabling cerebroprotection, brain tissue remodeling, and neurological recovery in young, healthy stroke mice. However, the translation of cell-based therapies to clinical settings has encountered challenges. It remained unclear if adult NPCs could induce brain tissue remodeling and recovery in mice with hyperlipidemia, a prevalent vascular risk factor in stroke patients.MethodsMale mice on a normal (regular) diet or on cholesterol-rich Western diet were exposed to 30 min intraluminal middle cerebral artery occlusion (MCAO). Vehicle or 106 NPCs were intravenously administered immediately after reperfusion, at 3 day and 7 day post-MCAO. Neurological recovery was evaluated using the Clark score, Rotarod and tight rope tests over up to 56 days. Histochemistry and light sheet microscopy were used to examine ischemic injury and brain tissue remodeling. Immunological responses in peripheral blood and brain were analyzed through flow cytometry.ResultsNPC administration reduced infarct volume, blood–brain barrier permeability and the brain infiltration of neutrophils, monocytes, T cells and NK cells in the acute stroke phase in both normolipidemic and hyperlipidemic mice, but increased brain hemorrhage formation and neutrophil, monocyte and CD4+ and CD8+ T cell counts and activation in the blood of hyperlipidemic mice. While neurological deficits in hyperlipidemic mice were reduced by NPCs at 3 day post-MCAO, NPCs did not improve neurological deficits at later timepoints. Besides, NPCs did not influence microglia/macrophage abundance and activation (assessed by morphology analysis), astroglial scar formation, microvascular length or branching point density (evaluated using light sheet microscopy), long-term neuronal survival or brain atrophy in hyperlipidemic mice.ConclusionsIntravenously administered NPCs did not have persistent effects on post-ischemic neurological recovery and brain remodeling in hyperlipidemic mice. These findings highlight the necessity of rigorous investigations in vascular risk factor models to fully assess the long-term restorative effects of cell-based therapies. Without comprehensive studies in such models, the clinical potential of cell-based therapies cannot be definitely determined.

A Modified Transcranial Middle Cerebral Artery Occlusion Model to Study Stroke Outcomes in Aged Mice.

In experimental stroke research, middle cerebral artery occlusion (MCAO) with an intraluminal filament is widely used to model ischemic stroke in mice. The filament MCAO model typically exhibits a massive cerebral infarction in C57Bl/6 mice that sometimes includes brain tissue in the territory supplied by the posterior cerebral artery, which is largely due to a high incidence of posterior communicating artery atresia. This phenomenon is considered a major contributor to the high mortality rate observed in C57Bl/6 mice during long-term stroke recovery after filament MCAO. Thus, many chronic stroke studies exploit distal MCAO models. However, these models usually produce infarction only in the cortex area, and consequently, the assessment of post-stroke neurologic deficits could be a challenge. This study has established a modified transcranial MCAO model in which the MCA at the trunk is partially occluded either permanently or transiently via a small cranial window. Since the occlusion location is relatively proximal to the origin of the MCA, this model generates brain damage in both the cortex and striatum. Extensive characterization of this model has demonstrated an excellent long-term survival rate, even in aged mice, as well as readily detectable neurologic deficits. Therefore, the MCAO mouse model described here represents a valuable tool for experimental stroke research.

Salt-induced maladaptive innate immune memory impedes stroke recovery

Abstract A high salt diet (HSD) is a top risk factor for human mortality. Beyond its heavily implicated role in hypertension, it is now linked to the development of inflammatory diseases before the onset of cardiovascular events. Even after salt reduction, HSD can induce prolonged tissue damage, yet the mechanisms by which HSD induces persistent negative effects on immune system are largely unexplored. While HSD is an established risk factor for stroke, its impact on long-term stroke recovery is unknown. Here, we model two major stroke types, intracerebral hemorrhage, and cerebral ischemia, to investigate how HSD induces unfavorable immune responses and subsequently impacts long-term tissue repair. We found HSD exclusively hampers alternative activation in monocytes-derived macrophages (MDMs) while sparing the major parenchymal macrophage—microglia—in the stroke brain. HSD induces innate immune memory in the hematopoietic stem and progenitor cells through downregulating mitochondrial oxidative phosphorylation and NR4a orphan nuclear receptors expression. This immunological memory was retained in the brain-infiltrating MDMs and restrained their reparative functions. Consequently lead to impaired tissue repair and neurobehavioral recovery during stroke recovery phase. Pharmacological treatment with NR4a1 activator and genetic overexpression of NR4a1 restored MDMs reparative phenotype suppressed by HSD and enabled stroke recovery. These findings establish a new mechanism linking HSD-induced maladaptive innate immune memory to a hindered macrophage alternative activation and delayed tissue recovery. Our data unveil innate immune memory and NR4a1 as potential therapeutic targets for treating HSD-associated diseases.

Poststroke Intravenous Transplantation of Human Mesenchymal Stem Cells Improves Brain Repair Dynamics and Functional Outcomes in Aged Mice.

Stroke is the primary cause of chronic disability in the elderly, as there are no neurorestorative treatments for those who do not qualify for recanalization therapy. Experimental evidence in stroke animals suggests that transplantation of bone marrow-derived human mesenchymal stem cells (hMSCs) holds promise, but hMSC transplantation has not been systematically tested in aged animals. We tested the hypothesis that poststroke hMSC transplantation improves stroke recovery in aged mice by promoting brain repair. Permanent focal cerebral ischemia was induced in 20-month-old C57BL/6 male mice by distal middle cerebral artery occlusion. Bone marrow-derived hMSCs were expanded in vitro and then administrated intravenously into mice (1×106 cells in PBS) 24 hours after distal middle cerebral artery occlusion. Sensorimotor and cognitive functions, brain atrophy, and brain repair processes (neurogenesis, angiogenesis, oligodendrogenesis) were assessed for up to 56 days after stroke. Poststroke hMSC transplantation did not mitigate brain atrophy or improve neuronal survival at 56 days after distal middle cerebral artery occlusion. However, hMSC-treated mice displayed superior neurobehavioral performances in the open field, rotarod, adhesive removal, novel object, and Morris water maze tests compared with PBS-treated controls. hMSCs promoted white matter integrity and enhanced angiogenesis and oligodendrogenesis-but not neurogenesis-in the stroke brain. Positive correlations between neurobehavioral performance and brain repair profiles or white matter integrity were observed in stroke mice. Poststroke hMSC transplantation improves long-term stroke recovery in aged mice, likely via mechanisms involving enhanced microvascular regeneration and white matter restoration.

Platelet depletion does not alter long-term functional outcome after cerebral ischaemia in mice

Platelets are key mediators of thrombus formation and inflammation during the acute phase of ischaemic stroke. Particularly, the platelet glycoprotein (GP) receptors GPIbα and GPVI have been shown to mediate platelet adhesion and activation in the ischaemic brain. GPIbα and GPVI blockade could reduce infarct volumes and improve functional outcome in mouse models of acute ischaemic stroke, without concomitantly increasing intracerebral haemorrhage. However, the functional role of platelets during long-term stroke recovery has not been elucidated so far.Thus, we here examined the impact of platelet depletion on post-stroke recovery after transient middle cerebral artery occlusion (tMCAO) in adult male mice. Platelet depleting antibodies or isotype control were applied from day 3–28 after tMCAO in mice matched for infarct size. Long-term functional recovery was assessed over the course of 28 days by behavioural testing encompassing motor and sensorimotorical functions, as well as anxiety-like or spontaneous behaviour. Whole brain flow cytometry and light sheet fluorescent microscopy were used to identify resident and infiltrated immune cell types, and to determine the effects of platelet depletion on the cerebral vascular architecture, respectively.We found that delayed platelet depletion does not improve long-term functional outcome in the tMCAO stroke model. Immune cell abundance, the extent of thrombosis and the organisation of the cerebral vasculature were also comparable between platelet-depleted and control mice. Our study demonstrates that, despite their critical role in the acute stroke setting, platelets appear to contribute only marginally to tissue reorganisation and functional recovery at later stroke stages.

Abstract P814: Complex Movement Representations of Mouse Motor Cortex After Experimental Stroke

Stroke injury and incomplete long-term stroke recovery remain key health issues in the United States and world-wide. We seek to help identify cellular dysfunction of the motor cortex after stroke, and its possible circuit remodeling during stroke recovery, since this structure is heavily implicated in this biology. We propose to measure evoked motor responses during long-train intracortical microstimulation (LT-ICMS) of motor cortex in the mouse as a method to identify the functional organization of this structure and plasticity following experimental stroke that relates to functional recovery. This work is one of the first to use LT-ICMS in mice after experimental stroke and it is employed in this study because it evokes complex, multi-joint forelimb movements that may match the temporal activity patterns of motor cortical cells during volitional movement and relate to skilled motor behavior. Permanent stroke injury is induced here using photothrombotic occlusion of the distal middle cerebral artery (MCAo) using Rose Bengal dye and green laser photostimulation. Skilled motor behavior is tested using the single pellet reaching task. Each mouse completes 30 days of post-injury or sham-injury single pellet reaching that is followed by an evaluation of cortical forelimb movement representation using LT-ICMS and then histological testing of lesion size and location. LT-ICMS is delivered as 500 millisecond trains of biphasic 200 microsecond pulses (delivered at 333 Hz) via a platinum/iridium microelectrode. The microelectrode is applied to test sites across the motor cortex (354 micron spacing) that are each at a depth of 800 microns. Evoked movements to LT-ICMS are quantified using high-speed video kinematic tracking of the forelimb. Experimental blind conditions are maintained until study completion. Statistics are then used to relate outcomes of behavioral reaching, LT-ICMS, and lesion characteristics. Collectively, the goal of this project is to understand whether (and how) complex movement representations derived by LT-ICMS change during stroke recovery in order to guide rehabilitative and interventional stroke therapies.

Ultrasound Controlled Anti-Inflammatory Polarization of Platelet Decorated Microglia for Targeted Ischemic Stroke Therapy.

Stroke is a lethal cerebral disease with severe sequelae and high mortality. Microglia, the main immune cell in the cerebrum, possess therapeutic potential for strokes as its specific anti-inflammatory phenotype can reduce inflammation and promote neuron regeneration. However, the on-demand anti-inflammatory polarization of microglia at the stroke site is uncontrollable for therapeutic application. Here, we develop a platelet hybrid microglia platform which can specifically polarize to the anti-inflammatory phenotype by ultrasound irradiation for targeted cerebrum repair after stroke. The engineered microglia have strong adherence to the injured cerebral vessels with platelet membrane fusion and realize on-demand anti-inflammatory polarization with ultrasound-responsive IL-4 liposome decoration. The intravenously injected microglia platform showed anti-inflammatory polarization at the stroke site with insonation, and accelerated the M2-type polarization of endogenous microglia for long-term stroke recovery. Satisfied prognoses were achieved with reduced apoptosis, promoted neurogenesis, and functional recovery, indicating the implications of the microglia platform for stroke therapy.

Depression and Diabetes Mellitus Multimorbidity Is Associated With Loss of Independence and Dementia Poststroke.

Many patients with ischemic stroke present with multiple comorbidities that threaten survival and recovery. This study sought to determine the risks of adverse long-term stroke outcomes associated with multimorbid diabetes mellitus and depression. Retrospective analysis of prospectively collected data on consecutive patients without premorbid dementia admitted from the community for a first-ever acute ischemic stroke to comprehensive stroke centers across Ontario, Canada (2003-2013). Premorbid histories of diabetes mellitus and depression were ascertained within 5 years before stroke admission. Adjusted hazard ratios (aHR [95% CI]) of admission to long-term care, incident dementia, readmission for stroke or transient ischemic attack and all-cause mortality, over time among those discharged back into the community poststroke. Among 23 579 stroke admissions, n=20 201 were discharged back into the community. Diabetes mellitus and depression were associated with synergistic hazards of admission to long-term care (X2=5.4; P=0.02) over a median follow-up of 5.6 years. This interaction was observed among women specifically; depression multimorbidity showed particularly high hazards of admission to long-term care (aHRDepression=1.57 [1.24-1.98]) and incident dementia (aHRDepression=1.85 [1.40-2.44]) among women with diabetes mellitus. In the whole cohort, diabetes mellitus and depression were associated individually with long-term care admission (aHRDiabetes=1.20 [1.12-1.29]; aHRDepression=1.19 [1.04-1.37]), incident dementia (aHRDiabetes=1.14 [1.06-1.23]; aHRDepression=1.27 [1.08-1.49]), stroke/transient ischemic attack readmission (aHRDiabetes=1.18 [1.10-1.26]; aHRDepression=1.24 [1.07-1.42]), and all-cause mortality (aHRDiabetes=1.29 [1.23-1.36]; aHRDepression=1.16 [1.05-1.29]). The risks of dementia and needing long-term care in the years after surviving a stroke were particularly elevated among women when premorbid diabetes mellitus and depression occurred together. Long-term stroke recovery strategies might target high-risk patients with mood and metabolic multimorbidity.

Adaptive Immune Cells Link Microbial Metabolites to Stroke Recovery.

Ischemic stroke has pervasive effects outside the CNS, leading to a cascade of inflammatory events that drives multiorgan dysfunction and hampers long-term stroke recovery. Peripheral organs, such as the lung ([Mai et al., 2017][1], [2019][2]), heart ([Bieber et al., 2017][3]), and intestine ([Singh

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons.

Type 2 diabetes (T2D) hampers stroke recovery though largely undetermined mechanisms. Few preclinical studies have investigated the effect of genetic/toxin-induced diabetes on long-term stroke recovery. However, the effects of obesity-induced T2D are mostly unknown. We aimed to investigate whether obesity-induced T2D worsens long-term stroke recovery through the impairment of brain's self-repair mechanisms - stroke-induced neurogenesis and parvalbumin (PV)+ interneurons-mediated neuroplasticity. To mimic obesity-induced T2D in the middle-age, C57bl/6j mice were fed 12 months with high-fat diet (HFD) and subjected to transient middle cerebral artery occlusion (tMCAO). We evaluated neurological recovery by upper-limb grip strength at 1 and 6 weeks after tMCAO. Gray and white matter damage, stroke-induced neurogenesis, and survival and potential atrophy of PV-interneurons were quantitated by immunohistochemistry (IHC) at 2 and 6 weeks after tMCAO. Obesity/T2D impaired neurological function without exacerbating brain damage. Moreover, obesity/T2D diminished stroke-induced neural stem cell (NSC) proliferation and neuroblast formation in striatum and hippocampus at 2 weeks after tMCAO and abolished stroke-induced neurogenesis in hippocampus at 6 weeks. Finally, stroke resulted in the atrophy of surviving PV-interneurons 2 weeks after stroke in both non-diabetic and obese/T2D mice. However, after 6 weeks, this effect selectively persisted in obese/T2D mice. We show in a preclinical setting of clinical relevance that obesity/T2D impairs neurological functions in the stroke recovery phase in correlation with reduced neurogenesis and persistent atrophy of PV-interneurons, suggesting impaired neuroplasticity. These findings shed light on the mechanisms behind impaired stroke recovery in T2D and could facilitate the development of new stroke rehabilitative strategies for obese/T2D patients.

Abstract TP115: Cellular and Molecular Characterization of Microglia in Secondary Thalamic Injury After Ischemic Stroke

Introduction: Secondary thalamic injury develops progressively after cortical ischemic stroke. This secondary injury associates with somatosensory dysfunctions and hinders recovery. However, the underlying pathological mechanisms are unclear. Previously our time course histological study characterized neuronal degeneration and inflammatory responses in the secondary thalamic injury after cortical ischemic stroke. In this study, we further investigated the cellular and molecular changes of microglia during the development of secondary thalamic injury. Methods: Left middle cerebral artery was permanently occluded to generate cortical ischemic stroke on male C57BL6J mice. Brain sections were collected on post-stroke days (PD) 1, 3, 7, 14 and 28. Immunostaining was used to detect microglia/macrophage activation (Iba-1) in the ipsilesional thalamus (iTH). Flow cytometry was used to discriminate between microglia and peripheral macrophages at PD28. iTH at PD7 and PD28 were processed for NanoString neuropathology transcriptome analysis (780 genes) to investigate the molecular changes. Microglial activation related genes were validated by qPCR. Results: In iTH, very few activated microglia/macrophages were detected at PD1. Clusters of microglia/macrophages appeared at PD7, became denser at PD14 and peaked at PD28. Flow cytometry analysis confirmed that at PD28, most of the microglial/macrophage population in iTH was CD11b + CD45 low , indicating they were mainly resident microglia. Furthermore, a subtype of CD11c+ microglia population were identified in iTH. NanoString analysis revealed significant changes in iTH transcriptome, with 50 differentially expressed genes at PD7 and 191 at PD28 when compared to naive mice. Several microglial activation related genes (CX3CR1, CSF1R and TLR2) were significantly increased at PD28 iTH compared to naïve and PD7. Conclusion: We have characterized the cellular and molecular changes of microglia in secondary thalamic injury. We demonstrated that the activated microglia/macrophages in iTH were mainly resident microglia exhibiting increased microglial specific genes. Targeting microglial activation may alleviate secondary thalamic injury and promote long-term stroke recovery.

A large, open source dataset of stroke anatomical brain images and manual lesion segmentations

Stroke is the leading cause of adult disability worldwide, with up to two-thirds of individuals experiencing long-term disabilities. Large-scale neuroimaging studies have shown promise in identifying robust biomarkers (e.g., measures of brain structure) of long-term stroke recovery following rehabilitation. However, analyzing large rehabilitation-related datasets is problematic due to barriers in accurate stroke lesion segmentation. Manually-traced lesions are currently the gold standard for lesion segmentation on T1-weighted MRIs, but are labor intensive and require anatomical expertise. While algorithms have been developed to automate this process, the results often lack accuracy. Newer algorithms that employ machine-learning techniques are promising, yet these require large training datasets to optimize performance. Here we present ATLAS (Anatomical Tracings of Lesions After Stroke), an open-source dataset of 304 T1-weighted MRIs with manually segmented lesions and metadata. This large, diverse dataset can be used to train and test lesion segmentation algorithms and provides a standardized dataset for comparing the performance of different segmentation methods. We hope ATLAS release 1.1 will be a useful resource to assess and improve the accuracy of current lesion segmentation methods.

Role of sleep-disordered breathing and sleep-wake disturbances for stroke and stroke recovery.

Background:Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) are highly prevalent in stroke patients. Recent studies suggest that they represent both a risk factor and a consequence of stroke and affect stroke recovery, outcome, and recurrence.Methods:Review of literature.Results:Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in TIA and stroke patients are recommended in view of the very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of obstructive SDB with continuous positive airway pressure is recommended given the strength of the increasing evidence in support of a positive effect on outcome (Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB. Recently, both reduced and increased sleep duration, as well as hypersomnia, insomnia, and restless legs syndrome (RLS), were also suggested to increase stroke risk. Mainly experimental studies found that SWD may in addition impair neuroplasticity processes and functional stroke recovery. Treatment of SWD with hypnotics and sedative antidepressants (insomnia), activating antidepressants or stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias) are based on single case observations and should be used with caution.Conclusions:SDB and SWD increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome. Current knowledge supports the systematic implementation of clinical procedures for the diagnosis and treatment of poststroke SDB and SWD on stroke units.

Splenic responses in ischemic stroke: new insights into stroke pathology.

In the past decade, the significant contribution of the spleen to ischemic brain damage has gained considerable attention in stroke research. As the largest natural reservoir of immune cells, the spleen establishes critical connections with the ischemic brain during the progression of stroke and mobilizes its cells to the site of injury. Multiple "alarm" signals released from the injured brain are essential for the initiation of brain-spleen communication. Spleen-derived cells, including neutrophils, lymphocytes, and monocytes/macrophages, are known to contribute significantly to ischemic brain damage. Understanding the dynamic splenic responses to stroke will not only provide insights into the evolvement of ischemic brain injury but will also identify potential targets for stroke treatment. Here, we review recent studies on the functions of the spleen in ischemic stroke. We have included a discussion of several therapeutic strategies that target splenic responses and reduce acute ischemic brain damage in preclinical studies. Future investigations on the effects of the spleen on long-term stroke recovery are highly warranted.

Long-term recovery trajectory after stroke: an ongoing negotiation between body, participation and self

Purpose: Research has mainly focused on the first year of recovery trajectory after stroke, but there is limited knowledge about how stroke survivors manage their long-term everyday lives. This study seeks to fill this gap by exploring the long-term (1–13 years) negotiations of stroke survivors when they experience progress, wellbeing and faith in the future. Method: Repeated in-depth interviews were conducted with nine people living with moderate impairment after stroke and their closest relatives. Concepts from phenomenology and critical psychology constituted the frame of reference of the study. Results: The long-term stroke recovery trajectory can be understood as a process of struggling to overcome tensions between three phenomena under ongoing change: the lived body, participation in everyday life and sense of self. During the recovery process, stroke survivors experience progress, well-being and faith in the future when moving towards renewed relationships, characterised by (1) a modified habitual body, (2) repositioned participation in specific everyday life contexts and (3) a transformed sense of self. Conclusions: This study stresses the importance of developing new forms of professional support during the long-term recovery trajectory, to stimulate and increase interaction and coherence in the relationship between the stroke survivor's bodily perception, participation in everyday life and sense of self.Implications for RehabilitationThe study deepening how the long-term recovery trajectory after stroke is about ongoing embodied, practical and socially situated negotiations.The study demonstrates that the recovery trajectory is a long term process of learning where the stroke survivor, as an embodied agent, gradually modifies new bodily habits, re-position participation and transforming of the self.Health personnel are usually available in the acute and early rehabilitation period. The three phenomenons under ongoing change; “body”, “participation” and “self” are at this point just about being moved toward a renewed and a more coherent relationship in the stroke survivor long-lasting everyday life situated recovery trajectory.Available rehabilitation services at the municipal level supporting stroke survivors and relatives practical, social and interpersonal long-term challenges in everyday life can be important for minimizing their struggles and for promoting the experience progress, wellbeing and faith in the future.

Sleep Disturbance Impairs Stroke Recovery in the Rat

There is a lack of experimental evidence to support the hypothesis that sleep may modulate stroke outcome as suggested by clinical observations. We have previously shown that sleep disturbance (SDis) over 3 days aggravates brain damage in a rat model of focal cerebral ischemia. The aim of this study is to further investigate effects of SDis on long-term stroke recovery and neuroplasticity as assessed by axonal sprouting, neurogenesis, and angiogenesis. Focal cerebral ischemia was induced by permanent occlusion of the distal branches of middle cerebral artery. Twelve hours after initiation of ischemia, SDis was performed over 3 consecutive days (deprivation of 80% sleep during the 12-h light phase). Weekly assessments on sensorimotor function by the single pellet reaching test (SPR) were performed for 5 weeks after surgery. Axonal sprouting was evaluated by anterograde tracing with biotinylated dextran amine (BDA) and neurogenesis/angiogenesis by bromodeoxyuridine (BrdU) labelling along with cell-type markers. Control groups included ischemia without SDis, sham with SDis, and sham without SDis. Basic sleep research laboratory. Rats subjected to SDis after ischemia showed significantly less recovery of forearm motor skills during the post-stroke period of 5 weeks. This effect was accompanied by a substantial reduction in axonal sprouting, expression of synaptophysin, and the ischemia-stimulated neural and vascular cell proliferation. SDis has detrimental effects on functional and morphological/structural outcomes after stroke, suggesting a role of sleep in the modulation of recovery processes and neuroplasticity.

The initial acute phase response predicts long-term stroke recovery

Indicators of an acute phase response (APR) in acute ischemic stroke have been shown to correlate with infarct size and predict stroke recurrence. In this study, we examined how well the APR indicators predicted long-term stroke recovery compared with standard clinical predictors of recovery. Plasma levels of interleukin-6 (IL-6), fibrinogen, white blood cells (WBCs), and serum albumin were measured within 4+/-2 days of onset in 131 stroke patients who were free of apparent infections. Standard clinical predictors included initial National Institutes of Health Stroke Scale (NIHSS), infarct size on computed tomography (CT), and Glasgow scale. The individual correlations with 6-month Glasgow outcome were IL-6, 0.42; fibrinogen, 0.24; WBC, 0.35; albumin, 0.47; NIHSS, 0.53; infarct size, 0.19; and initial Glasgow, 0.57. (all P<.005). Multiple regression analysis yielded an adjusted R(2) of .31 for the APR indicators, compared with .38 for the clinical variables. These results indicate that the initial APR is highly correlated with 6-month stroke recovery and that this correlation approaches that observed with standard clinical predictors.