Acute Stage Of Stroke Research Articles

Preservation of Cerebellar Afferent Pathway May Be Related to Good Hand Function in Patients with Stroke.

Many chronic stroke patients suffer from worsened hand function, and functional recovery of the hand does not occur well after six months of stroke. Therefore, predicting final hand function after stroke through acute phase imaging would be an important issue in counseling with the patients or their family. Thus, we investigated the remaining white matter integrity in the corticospinal tract (CST) and cortico-ponto-cerebellar tract (CPCT) at the acute stage of stroke and chronic hand function after stroke, and present the cut-off value of fiber number (FN) and fractional anisotropy (FA) of CST and CPCT at the acute stage for predicting final hand function after the recovery period. This retrospective case-control study included 18 stroke patients who were classified into two groups: poor hand function with stroke (n = 11) and good hand function with stroke (n = 7). DTI was done within two months ± 15 days after onset, and the Jebson’s Hand Function test was conducted 6–12 months after onset. The investigation of white matter was focused on the values of FN and FA for CST and CPCT, which were measured separately. The normalized (affected/non-affected) FA and FN values in the CPCT in the good hand function group were higher than those in the poor hand function group. The normalized FN and FA values in the CST were not significantly different between the poor hand function group and the good hand function group. The normalized cut-off value that distinguished the good hand function group from the poor hand function group was 0.8889 for FA in the CPCT. The integrity of the CPCT in the acute stage was associated with hand function in the chronic stage after a stroke. Ultimately, the integrity of the CPCT in the early stage after onset can be used to predict chronic hand function. Based on these results, cerebellar afferent fiber measurements may be a useful addition to predict hand function and plan specific rehabilitation strategies in stroke patients.

The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke.

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response via cytokine signaling, are the first cell population to become activated. Soon after, monocytes arrive from the peripheral immune system, differentiate into macrophages, and further aid in the immune response. Upon activation, both microglia and monocyte-derived macrophages are capable of polarizing into phenotypes which can either promote or attenuate the inflammatory response. Phenotypes which promote the inflammatory response are hypothesized to increase neuronal damage and impair recovery of neuronal function during the later phases of ischemic stroke. Therefore, modulating neuroimmune cells to adopt an anti-inflammatory response post ischemic stroke is an area of current research interest and potential treatment development. In this review, we outline the biology of microglia and monocyte-derived macrophages, further explain their roles in the acute, subacute, and chronic stages of ischemic stroke, and highlight current treatment development efforts which target these cells in the context of ischemic stroke.

Harnessing cortical plasticity via gabapentinoid administration promotes recovery after stroke.

Stroke causes devastating sensory-motor deficits and long-term disability due to disruption of descending motor pathways. Restoration of these functions enables independent living and therefore represents a high priority for those afflicted by stroke. Here, we report that daily administration of gabapentin, a clinically approved drug already used to treat various neurological disorders, promotes structural and functional plasticity of the corticospinal pathway after photothrombotic cortical stroke in adult mice. We found that gabapentin administration had no effects on vascular occlusion, haemodynamic changes nor survival of corticospinal neurons within the ipsilateral sensory-motor cortex in the acute stages of stroke. Instead, using a combination of tract tracing, electrical stimulation and functional connectivity mapping, we demonstrated that corticospinal axons originating from the contralateral side of the brain in mice administered gabapentin extend numerous collaterals, form new synaptic contacts and better integrate within spinal circuits that control forelimb muscles. Not only does gabapentin daily administration promote neuroplasticity, but it also dampens maladaptive plasticity by reducing the excitability of spinal motor circuitry. In turn, mice administered gabapentin starting 1 h or 1 day after stroke recovered skilled upper extremity function. Functional recovery persists even after stopping the treatment at 6 weeks following a stroke. Finally, chemogenetic silencing of cortical projections originating from the contralateral side of the brain transiently abrogated recovery in mice administered gabapentin, further supporting the conclusion that gabapentin-dependent reorganization of spared cortical pathways drives functional recovery after stroke. These observations highlight the strong potential for repurposing gabapentinoids as a promising treatment strategy for stroke repair.

Serpine1 Regulates Peripheral Neutrophil Recruitment and Acts as Potential Target in Ischemic Stroke.

IntroductionPeripheral neutrophil infiltration can exacerbate ischemia–reperfusion injury. We focused on the relationship between various peripheral immune cells and cerebral ischemia–reperfusion (I/R) injury.MethodsIn this study, we investigated the effects of dauricine on neuronal injury induced by ischemia–reperfusion and peripheral immune cells after ischemic stroke in mouse model, and we explored the undefined mechanisms of regulating peripheral immune cells through RNA sequencing and various biochemical verification in vitro and in vivo.ResultsWe found that dauricine improved the neurological deficits of I/R injury, reduced the infarct volume, and improved the neurological scores. Furthermore, dauricine reduced the infiltration of neutrophils into the brain after MCAO-R and increased peripheral neutrophils but unchanged the permeability of the endotheliocyte Transwell system in an in vitro blood-brain barrier (BBB) model. RNA sequencing showed that chemotaxis factors, such as CXCL3, CXCL11, CCL20, CCL22, IL12a, IL23a, and serpine1, might play a crucial role. Overexpression of serpine1 reversed LPS-induced migration of neutrophils. Dauricine can directly bind with serpine1 in ligand–receptor docking performed with the Autodock and analyzed with PyMOL.ConclusionWe identified chemotaxis factor serpine1 played a crucial role in peripheral neutrophil infiltration, which may contribute to reduce the neuronal injury induced by ischemia–reperfusion. These findings reveal that serpine1 may act as a potential treatment target in the acute stage of ischemic stroke.

FLAIR vessel hyperintensities predict functional outcomes in patients with acute ischemic stroke treated with medical therapy.

The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. • FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.

Prognosis associated with asymptomatic intracranial hemorrhage after acute ischemic stroke: a systematic review and meta-analysis.

It remains inconclusive whether asymptomatic intracranial hemorrhage (aICH) after acute ischemic stroke is innocuous. We aimed to conduct a meta-analysis assessing the relationship between the aICH and poor neurological outcomes. We searched PubMed, EMBASE and Web of Science from their inception to 30 November 2021 and performed a meta-analysis on the association between the aICH and neurological prognosis after acute ischemic stroke at 3months, including poor outcomes (modified Rankin Scale [mRS] score ≥ 2 or mRS ≥ 3) and mortality. Fourteen studies were included in the analysis, reporting on a total of 10,915 participants after acute ischemic stroke. The risks of poor outcome (mRS ≥ 2 or mRS ≥ 3) in patients with aICH were significantly higher than patients without ICH (OR 1.70, 95% CI 1.33-2.18; OR 1.43, 95% CI 1.20-1.70, respectively), based on adjusted data. The difference between the two groups was not significant for mortality. The results of subgroup analysis showed aICH were associated with higher ratio of mild poor prognosis (mRS ≥ 2) (OR 1.59, 95% CI 1.11-2.27), but it had no association with functional dependence (mRS ≥ 3) after recanalization. No significant influence of aICH on poor outcome (mRS ≥ 3) was found in non-recanalization group. Further stratified analysis revealed that only aICH with patients receiving endovascular therapy (EVT) could increase the risk of mild poor prognosis (mRS ≥ 2) at 3months. Our results indicate that compared with patients without ICH, those who developed aICH during the acute stage of ischemic stroke had an increasing risk of worse outcome, especially in patients with endovascular therapy.

Global Metabolomic Profiling Reveals Disrupted Lipid and Amino Acid Metabolism Between the Acute and Chronic Stages of Ischemic Stroke

BackgroundStroke is a major cause of serious disability in the United States. Previous studies found multiple associations of serum metabolites with acute ischemic stroke (AIS) compared to controls, but few of them evaluated metabolome in a longitudinal fashion. Therefore, we compared the metabolome of the acute and chronic stages of ischemic stroke. MethodsWe evaluated 1295 serum metabolites from the cohort of 60 stroke patients at acute and chronic stages by performing global metabolomics using ultra-high-performance liquid chromatography/mass spectrometry (LC-MS) and gas chromatography/mass spectrometry (GC-MS). We used Orthogonal Partial Least Square-Discrimination Analysis (OPLS-DA) to inspect group disparity and a mixed regression model to compare metabolites in the acute and chronic stages with Two-Stage Benjamini & Hochberg (TSBH) and Bonferroni correction for multiple testing. ResultsThe OPLS-DA revealed significant separation of acute and chronic stage metabolites. Mixed regression identified 228 metabolites with TSBH, and 29 metabolites with Bonferroni correction different in acute and chronic stages. At the acute stage, there was a consistent increase of the metabolites of mono/diacylglycerols, sphingolipids, medium/long-chain fatty acids, and amino acids glycine, valine, and tyrosine. At the same time, there was a consistent decrease of the metabolites of acyl-choline related fatty acids, phospholipids, and amino acids alanine, aspartate, and tyramine. Additionally, we identified eight novel metabolites significantly altered at the acute stage of stroke. ConclusionOur pilot study demonstrated significant alterations in metabolomic patterns between the acute and chronic stages of stroke, validating some case-control findings. Future investigation in a larger independent cohort is warranted to identify early biomarkers of acute ischemic stroke.

SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression

BackgroundAbnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression.MethodsWe reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches.ResultsThe stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice.ConclusionsThis study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection.Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.

VEGF, a Key Factor for Blood Brain Barrier Injury After Cerebral Ischemic Stroke.

Blood brain barrier (BBB) injury is an important factor affecting the prognosis of ischemic stroke. Extensive research on BBB injury has revealed that blood vessels and neural networks are interdependent and interrelated during and after the development of the brain. An array of signaling molecules, known as angioneurins, can affect both blood vessels and neural networks simultaneously. Angioneurins not only regulate the angiogenesis and remodeling process of the vascular system, but also act as neurotrophic and neuroprotective factors, or serve as guide molecules for axons. Vascular endothelial growth factor (VEGF) is a type of angioneurin that is expressed in neurons, astrocytes, macrophages, and vascular endothelial cells in ischemic and hypoxic brain tissues after cerebral ischemia. VEGF can increase and induce the destruction of the endothelial barrier in the early stages of cerebral ischemia. Both the upregulation of endogenous VEGF levels and the use of exogenous VEGF are harmful in the acute stage of stroke. However, the harmful effects of VEGF on vascular integrity are transient. Several studies have shown that VEGF regulates angiogenesis, neurogenesis, neurite growth and brain edema after cerebral ischemia. Therefore, it is crucial to understand the dual role of VEGF in ischemic stroke. The following will focus on the damage caused by VEGF to the BBB in the context of cerebral ischemic stroke, as well as therapeutic studies targeting VEGF.

Assessment of the Diagnostic Value of Plasma Level of Von Willebrand Factor and ADAMTS13 in Patients with Cerebral Infarction

Background: Von Willebrand Factor (VWF) is a large multimeric plasma gly-coprotein that plays an important role in primary haemostasis. VWF together with ADAMTS13 plays a key role in arterial thrombosis. VWF is integral for platelet adhesion to collagen fibres and atherosclerotic plaues and platelets aggregation under high shear conditions. Upon vascular wall damage, plasma VWF binds to collagen in the exposed endothelial matrix and platelet glycoprotein triggers platelet aggregation and thrombous formation. In the early stages of acute ischaemic stroke, VWF increased significantly and the ADAMTS13 level decreased. The increase of plasma VWF and FVIII in a patient with ischaemic stroke indicated an increased risk of complications and severe neurological deficit. Objective: to evaluate the validity of VWF and ADFAMTS13 as diagnostic markers of cerebral infarction by comparing the two markers’ validity in diagnosis. Methods: this case control study enrolled 38 cerebral infarction patients 20 acute infarction and 18 recurrent infarction. Patients were compared with 65 age and sex with control patients. We performed the VWF assay using the minividas immunofluorescence technique and the ADAMTS13 assay using the ELISA technique. Results: VWF level of acute infarction patients (280.97 ± 109.83 IU/dl) while its level in recurrent infarction (264.93 ± 172.8 IU/dl) were highly significantly increased compared to control (75.8 ± 16.24 IU/dl). ADAMTS13 level of acute infarction patients was (506.11 ± 225.24 ng/dl) and (1386.03 ± 667.64 ng/dl) in recurrent infarction patients with highly significant differences between the acute and control group and non-significant different between recurrent and control. ADAMTS13 is an excellent diagnostic test in acute cerebral infarction but a weak diagnostic test in recurrent cerebral infarction but it is a good diagnostic test in differentiation between acute and recurrent cerebral infarction patients. VWF is an excellent diagnostic test in both acute and recurrent cases. In acute infarction, VWF is positively correlated with kidney function while ADAMTS13 level did not correlate with different laboratory parameters in recurrent infarction. A positive correlation is present between ADAMTS13 and PT & PTT concentration. No correlation exists between VWF & ADAMTS13 in the 3 groups. Conclusion: ADAMTS13 is closely related to the occurrence, development and progression of acute cerebral infarction, protecting the brain from ischaemic reperfusion injury. It is an excellent diagnostic test in acute cerebral infarction but a weak diagnostic test in recurrent cerebral infarction while VWF is an excellent diagnostic test in acute & recurrent cerebral infarction. ADAMTS13 is expected to become a new therapeutic agent in acute cerebral infarction patients.

Changes to Inclusion Criteria and Treatment Outcomes of STA-MCA Bypass during the Acute Stage of Progressive Stroke

Changes to Inclusion Criteria and Treatment Outcomes of STA-MCA Bypass during the Acute Stage of Progressive Stroke

Novel quantitative hemodynamic parameters in ischemic stroke: agreement for the acute and chronic stroke stage

Novel quantitative hemodynamic parameters in ischemic stroke: agreement for the acute and chronic stroke stage

Factors associated with oral intake ability in patients with acute-stage stroke

To investigate the factors predicting oral feeding ability following acute stroke. This retrospective study compared patients admitted to a stroke care unit in 2 groups: an oral intake group and a tube feeding group. The groups were evaluated for 28 items and initial blood investigation tests, and the results compared. Logistic regression analysis was used to identify the clinical variables significantly associated with oral feeding ability. A total of 255 stroke patients (162 in the oral intake group and 93 in the tube feeding group) were admitted to the stroke care unit. Significant differences were observed between the 2 groups for 20 items. Logistic analysis found that the following variables were significant in the prediction model: age, date of initiation of oral feeding, stroke recurrence/patient deterioration during hospitalization, and date of initiation of occupational therapy. Factors associated with achieving oral intake among stroke care unit patients were: young age at time of admission; starting oral intake early; no stroke recurrence/patient deterioration during hospitalization; and achieving rehabilitation of daily activities early during the physical function recovery stage.

Associations between stroke severity, aphasia severity, lesion location, and lesion size in acute stroke, and aphasia severity one year post stroke

ABSTRACT Background The aim of the present study was to investigate the associations stroke severity, aphasia severity, lesion location and lesion size in acute stroke, and aphasia severity in the subacute and chronic stages post stroke. We hypothesized that initial stroke severity and aphasia severity were associated with the patient’s aphasia severity in the subacute and chronic stages of stroke. We expected to find that lesions within the left frontotemporal regions of the brain were associated with aphasia severity post-stroke. Methods Thirty-three patients with aphasia were included in the study. They were assessed with a standardized aphasia test at admission to the hospital (T1), after 3 months (T2) and finally after 12 months (T3). Stroke severity, initial physical impairment, and initial functional independence were also assessed at T1. Diffusion-weighted magnetic resonance imaging was performed as clinical-routine at admission. Voxel-based lesion symptom mapping and a region of interest analysis (ROI) was performed to analyze MRI-findings. Results & Outcomes Initial lesion size and aphasia severity were associated with aphasia severity at T2. Initial stroke severity, aphasia severity, and lesion size were not associated with aphasia severity at T3, but the patients’ aphasia severity at T2 predicted aphasia severity at T3. Lesion analysis showed that lesions within the left postcentral gyrus and the left inferior parietal gyrus were significantly associated with aphasia severity at T3. The ROI-analysis did not yield any significant regions of interest to explain the total variance of the patients’ change in scores on the aphasia test from T1 to T3. Conclusion Lesions within the postcentral gyrus and the inferior parietal gyrus are associated with aphasia severity at T3. Lesion size in the acute stages of stroke is associated with aphasia severity at T1 and T2, but not T3. However, neither initial aphasia severity nor stroke severity was associated with aphasia severity at T3. Aphasia severity in T2 is however strongly associated with aphasia severity in T3.

The Role of Immune Cells in Post-Stroke Angiogenesis and Neuronal Remodeling: The Known and the Unknown.

Following a cerebral ischemic event, substantial alterations in both cellular and molecular activities occur due to ischemia-induced cerebral pathology. Mounting evidence indicates that the robust recruitment of immune cells plays a central role in the acute stage of stroke. Infiltrating peripheral immune cells and resident microglia mediate neuronal cell death and blood-brain barrier disruption by releasing inflammation-associated molecules. Nevertheless, profound immunological effects in the context of the subacute and chronic recovery phase of stroke have received little attention. Early attempts to curtail the infiltration of immune cells were effective in mitigating brain injury in experimental stroke studies but failed to exert beneficial effects in clinical trials. Neural tissue damage repair processes include angiogenesis, neurogenesis, and synaptic remodeling, etc. Post-stroke inflammatory cells can adopt divergent phenotypes that influence the aforementioned biological processes in both endothelial and neural stem cells by either alleviating acute inflammatory responses or secreting a variety of growth factors, which are substantially involved in the process of angiogenesis and neurogenesis. To better understand the multiple roles of immune cells in neural tissue repair processes post stroke, we review what is known and unknown regarding the role of immune cells in angiogenesis, neurogenesis, and neuronal remodeling. A comprehensive understanding of these inflammatory mechanisms may help identify potential targets for the development of novel immunoregulatory therapeutic strategies that ameliorate complications and improve functional rehabilitation after stroke.

Bidirectional Benign Regulation of Acupuncture in the Treatment of Stroke

Acupuncture is a traditional Chinese medicine therapy originated in China. In recent years, acupuncture is widely used in the field of neurological diseases, especially in the acute stage of stroke. Its mechanism of action is becoming clearer; one of the possible mechanisms is its bidirectional benign regulation.

Comparative Characterization of Candidate Molecular Markers in Ischemic and Hemorrhagic Stroke

According to epidemiological studies, the leading cause of morbidity, disability and mortality are cerebrovascular diseases, in particular ischemic and hemorrhagic strokes. In recent years considerable attention has been given to the study of molecular markers of ischemic and hemorrhagic strokes. These studies are relevant because brain-specific protein biomarkers of neurons and glial cells can provide valuable and timely diagnostic information necessary for clinical decision-making.The aim of the study was to reveal the differences in the serum level of molecular markers in acute, subacute and early recovery periods of ischemic and hemorrhagic strokes.Material and methods. The study included 59 patients. Twenty patients were diagnosed with hemorrhagic stroke and 39 had ischemic stroke. The control group included 20 volunteers. Serum levels of molecular CNS markers were determined in acute, subacute, and early recovery stages of stroke. The serum levels of CNS molecular markers of patients with ischemic and hemorrhagic stroke was measured quantitatively by enzyme immunoassay. Statistical analysis was performed by nonparametric Mann-Whitney method.Results. The level of brain-derived neurotrophic factor (BDNF) in the control volunteers was 574.5 [455.5; 615] pg/ml. Significant differences were found for acute and subacute periods of hemorrhagic stroke: it was 674 [560; 749] pg/ml (P=0.003) and 664 [616; 762] pg/ml (P=0.0001).The level of neuron-specific enolase was significantly increased in all periods of the study: it was 4.15 [3.53; 4.8] ng/ml in the control group, 5.4 [4.4; 6.4] ng/ml in acute period of ischemic stroke (P&lt;0.001), 5.4 [4.4; 6.4] ng/ml in early recovery period of ischemic stroke (P=0.001), 5.1 [4.6; 6.4] ng/ml in acute period of hemorrhagic stroke (P=0.014), 664 [616; 762] ng/ml in subacute period of hemorrhagic stroke (P=0.003).In the control group, the serum S-100 protein level was 4.5 [3.8; 5.4] ng/ml. In the acute and early recovery periods of ischemic stroke, S-100 protein level has significantly fallen down to 4.1 [3.4; 4.6] ng/ml (P&lt;0.031) and 3.9 [3.4; 6] ng/ml (P=0.014), respectively. Glial-cell derived neurotrophic factor level was 1.98 [1.64; 2.1] ng/ml in the controls and increased up to 2.4 [2.2; 5] ng/ml (P=0.002) in the acute period and 2.4 [2.3; 2.6] ng/ml (P&lt;0.001) in the subacute period of hemorrhagic stroke.The vascular endothelial growth factor receptor-1 (VEGFR-1) was significantly lower in the subacute period of hemorrhagic stroke: 485 [211; 945] pg/ml in the subacute period vs 903.5 [626; 1115] pg/ml in the controls (P=0.001).Conclusion. We found differences in the serum level of molecular markers in patients with ischemic and hemorrhagic strokes. In the acute period, early recovery period of ischemic stroke, and subacute period of hemorrhagic stroke, there was an increase in the serum level of neuron-specific enolase. The level of brain-derived neurotrophic factor increased significantly in the acute and subacute periods of hemorrhagic stroke. In the acute and early recovery periods of ischemic stroke, the level of S-100 protein decreased. The level of glial cell-derived neurotrophic factor increased in the acute and subacute periods of hemorrhagic stroke. In the subacute period of hemorrhagic stroke, the level of endothelial growth factor receptor-1 significantly decreased. Moreover, there was significant difference between values of this parameter in the subacute period of hemorrhagic stroke and in the early recovery period of ischemic stroke.

Day-by-Day Blood Pressure Variability in the Subacute Stage of Ischemic Stroke and Long-Term Recurrence.

This study aimed to determine whether variability of day-by-day blood pressure (BP) during the subacute stage of acute ischemic stroke is predictive of long-term stroke recurrence. We analyzed 7665 patients (mean±SD age: 72.9±13.1 years; women: 42.4%) hospitalized for first-ever ischemic stroke in 7 stroke centers in Fukuoka, Japan, from June 2007 to November 2018. BP was measured daily during the subacute stage (4-10 days after onset). Its mean and coefficient of variation (CV) values were calculated and divided into 4 groups according to the quartiles of these BP parameters. Patients were prospectively followed up for recurrent stroke or all-cause death. The cumulative event rate was calculated with the Kaplan-Meier method. We estimated the hazard ratios and 95% confidence intervals of the events of interest after adjusting for potential confounders and mean BP values using Cox proportional hazards models. The Fine-Gray model was also used to account for the competing risk of death. With a mean (±SD) follow-up duration of 3.9±3.2 years, the rates of recurrent stroke and all-cause death were 3.9 and 9.9 per 100 patient-years, respectively. The cumulative event rates of recurrent stroke and all-cause death increased with increasing CVs of systolic BP and diastolic BP. The systolic BP CV was significantly associated with an increased risk of recurrent stroke after adjusting for multiple confounders and mean BP (hazard ratio [95% CI] for fourth quartile versus first quartile, 1.26 [1.05-1.50]); the risk of recurrent stroke also increased with an increasing systolic BP CV for nonfatal strokes (1.26 [1.05-1.51]) and when death was regarded as a competing risk (1.21 [1.02-1.45]). Similar associations were observed for the diastolic BP CV. Day-by-day variability of BP during the subacute stage of acute ischemic stroke was associated with an increased long-term risk of recurrent stroke.

Vagus nerve stimulation mediates microglia M1/2 polarization via inhibition of TLR4 pathway after ischemic stroke

Ischemic stroke is the leading cause of death and disability. Microglia are polarized toward the proinflammatory M1 phenotype and neuroprotective M2 phenotype after stroke and play an important role in the pathological process of ischemic stroke. Emerging research suggests that vagus nerve stimulation (VNS) can mediate microglia polarization after ischemic stroke and may serve as a potential treatment for ischemic stroke. However, the mechanism by which VNS mediates microglia polarization remains unclear. In this study, we aimed to investigate the underlying mechanism. Sprague-Dawley rats were randomly divided into the sham, ischemic stroke, ischemic stroke + VNS, ischemic stroke + VNS + lentivirus (LV)-TLR4 and ischemic stroke + VNS + LV-CON groups. LV was injected into the lateral ventricles of the rats 14 days before ischemic stroke surgery, and VNS was administered after 30 min of occlusion. We assessed the infarct volume, neurological scores, the TLR4/MyD88/NF-κB protein level and microglia polarization after 3 days of reperfusion. Our results revealed that VNS can promote M2 microglia polarization and inhibit M1 microglia polarization to alleviate brain injury via inhibition of the TLR4/MyD88/NF-κB pathway in microglia in the acute stage of stroke.

Utilization of Robotic Exoskeleton for Overground Walking in Acute and Chronic Stroke.

Stroke commonly results in gait deficits which impacts functional ambulation and quality of life. Robotic exoskeletons (RE) for overground walking are devices that are programmable to provide high dose and movement-impairment specific assistance thus offering new rehabilitation possibilities for recovery progression in individuals post stroke. The purpose of this investigation is to present preliminary utilization data in individuals with acute and chronic stroke after walking overground with an RE. Secondary analysis on a subset of individuals is presented to understand the mechanistic changes due to RE overground walking. Thirty-eight participants with hemiplegia secondary to stroke were enrolled in a clinical trial conducted at eight rehabilitation centers. Data is presented for four sessions of overground walking in the RE over the course of 2 weeks. Participants continued their standard of care if they had any ongoing therapy at the time of study enrollment. Gait speed during the 10 Meter Walk Test, Gait deviations and the Functional Ambulation Category (FAC) data were collected before (baseline) and after (follow-up) the RE walking sessions. Walking speed significantly increased between baseline and follow-up for participants in the chronic (p <0.01) and acute (p < 0.05) stage of stroke recovery. FAC level significantly improved (p < 0.05) and there were significantly fewer (p < 0.05) gait deviations observed for participants in the acute stages of stroke recovery between baseline and follow-up. Secondary analysis on a subset of eight participants indicated that after four sessions of overground walking with the RE, the participants significantly improved their spatial symmetry. The walk time, step count and ratio of walk time to up time increased from first session to the last session for participants in the chronic and acute stages of stroke. The RE was effectively utilized for overground walking for individuals with acute and chronic stroke with varying severity levels. The results demonstrated an increase in walking speed, improvement in FAC and a decrease in gait deviations (from baseline to follow-up) after four sessions of overground walking in the RE for participants. In addition, preliminary data indicated that spatial symmetry and step length also improved after utilization of an RE for overground walking.