Acute Phase Of Ischemic Stroke Research Articles

High neutrophil percentage and neutrophil-lymphocyte ratio in acute phase of ischemic stroke predict cognitive impairment: A single-center retrospective study in China.

Background and aimsRecently, various hemocyte and blood cell ratios have garnered researchers' attention, as a low-cost, widely prevalent, and easy-to-measure index for diagnosing and predicting disease. Therefore, we sought to investigate the effect and predictive value of the peripheral blood neutrophil percentage and neutrophil-lymphocyte ratio (NLR) in the acute phase of ischemic stroke (AIS) in post-stroke cognitive impairment (PSCI).MethodsWe selected 454 patients with mild AIS and acquired general clinical data. The patients were divided into PSCI and post-stroke no cognitive impairment (PSNCI) groups according to their Montreal Cognitive Assessment (MOCA) scores. We assessed whether there were differences in clinical data, peripheral blood neutrophil percentage, and NLR values between the different groups. We also analyzed the independent influences on the occurrence of PSCI using a binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the above inflammatory indicators and models containing different inflammatory indicators for PSCI.ResultsIn total, 454 patients were included, of whom 253 (55.7%) patients were in the PSCI group, with a mean age of 62.15 ± 7.34 years and median neutrophil percentage and NLR of 0.64 (0.32–0.95) and 2.39 (0.71–54.46), respectively. Both neutrophil percentage (adjusted OR = 1.025; 95% confidence interval: 1.005–1.406) and NLR as a categorical variable (Q5, adjusted OR = 2.167; 95% CI: 1.127–4.166) were independent risk factors for PSCI, and the Q5 group (NLR ≥ 4.05) had significantly worse overall cognition and executive function.ConclusionsNeutrophil percentage and NLR in the acute phase of AIS were independently associated with PSCI, and a high NLR was strongly associated with executive function. In addition, neutrophil percentage and NLR have diagnostic values for PSCI.

Diagnostic Yield of ECG-Gated Cardiac CT in theAcute Phase of Ischemic Stroke vsTransthoracic Echocardiography.

Guidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE). We performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations. Between May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5-7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28-16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%). Cardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

SPP1/AnxA1/TIMP1 as Essential Genes Regulate the Inflammatory Response in the Acute Phase of Cerebral Ischemia-Reperfusion in Rats.

BackgroundIschemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear.MethodsGene expression profiles of two rat ischemic stroke-related data sets, GSE61616 and GSE97537, were downloaded from the GEO database for Gene Set Enrichment Analysis (GSEA). Then, GEO2R was used to screen differentially expressed genes (DEGs). Furthermore, 170 differentially expressed intersection genes were screened and analyzed for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Candidate genes and miRNAs were obtained by DAVID, Metascape, Cytoscape, STRING, and TargetScan. Finally, the rat middle cerebral artery occlusion-reperfusion (MCAO/R) model was constructed, and qRT-PCR was used to verify the predicted potential miRNA molecule and its target genes.ResultsGO and KEGG analyses showed that 170 genes were highly associated with inflammatory cell activation and cytokine production. After cluster analysis, seven hub genes highly correlated with post-stroke neuroinflammation were obtained: Cxcl1, Kng1, Il6, AnxA1, TIMP1, SPP1, and Ccl6. The results of TargetScan further suggested that miR-340-5p may negatively regulate SPP1, AnxA1, and TIMP1 simultaneously. In the ischemic penumbra of rats 24 h after MCAO/R, the level of miR-340-5p significantly decreased compared with the control group, while the concentration of SPP1, AnxA1, and TIMP1 increased. Time-course studies demonstrated that the mRNA expression levels of SPP1, AnxA1, and TIMP1 fluctuated dramatically throughout the acute phase of cerebral ischemia-reperfusion (I/R).ConclusionOur study suggests that differentially expressed genes SPP1, TIMP1, and ANXA1 may play a vital role in the inflammatory response during the acute phase of cerebral ischemia-reperfusion injury. These genes may be negatively regulated by miR-340-5p. Our results may provide new insights into the complex pathophysiological mechanisms of secondary inflammation after stroke.

The relationship between red blood cell distribution width at admission and post-stroke fatigue in the acute phase of acute ischemic stroke.

IntroductionPost-stroke fatigue (PSF) is a common complication in the patients with acute ischemic stroke (AIS). This prospective study aimed to investigate the relationship between red blood cell distribution width (RDW) at admission and PSF in the acute phase.MethodsThe AIS patients were enrolled in Nantong Third People's Hospital, consecutively. PSF in the acute phase was scored according to the Fatigue Severity Scale. Levels of RDW were measured at admission. The associations were analyzed using multivariate regression and restricted cubic splines (RCS).ResultsFrom April 2021 to March 2022, a total of 206 AIS patients (mean age, 69.3 ± 10.7 years; 52.9% men) were recruited. After the adjustment for potential confounding factors, RDW at admission remained the independent associated factor with PSF in the acute phase (OR [odds ratio], 1.635; 95% CI [confidence interval], 1.153–2.318; P = 0.006). The linear dose-response associations of RDW with PSF in the acute phase were found, based on the RCS model (P for non-linearity = 0.372; P for linearity = 0.037). These results remained significant in other models.ConclusionsRDW at admission could serve as a novel biomarker of PSF in the acute phase of AIS.

Clinical Evidence of Acetyl-L-Carnitine Efficacy in the Treatment of Acute Ischemic Stroke: A Pilot Clinical Trial.

Background This study was undertaken to evaluate the influence of oral Acetyl-L-carnitine (ALC) in patients with acute ischemic stroke. Methods Sixty-nine cases with acute ischemic stroke with the onset of symptoms less than 24 hours not candidates for reperfusion therapy were randomly assigned to either the ALC group (1000 mg three times per day for three consecutive days) or the matching placebo group. The study outcomes based on intention-to-treat criteria included the change in the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 90, as well as the change in serum levels of the inflammatory and oxidative stress biomarkers over the 3-day treatment protocol. Results The NIHSS score and mRS score on day 90 were improved by 5.82 and 0.94 scores, respectively, in the ALC-treated group compared to 2.83 and 0.11 scores, respectively, in the placebo-treated group, which demonstrated the superiority of ALC relative to placebo. By using the multivariable analysis after adjusting for other variables in the model, compared to the group treated with placebo, patients in the ALC group had lower NIHSS score (β: -2.40, 95% CI: -0.69, -4.10 (p = 0.007)) and mRS score (β: -1.18, 95% CI: -0.52, -1.84 (p = 0.001)) 90 days after the intervention. The percentage of patients with a favourable functional outcome at day 90, defined as mRS scores of 0 or 1, was significantly higher in the ALC group in comparison to the placebo group (52.9% versus 28.6%). Further, over the 3-day treatment protocol, in the patients receiving ALC, the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and neuron-specific enolase (NSE), showed a significant decrease, while the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L-carnitine's level showed a significant increase compared to those in patients receiving placebo indicating significant alteration. Conclusions Although preliminary, these results suggested that ALC administration during the acute phase of ischemic stroke might be helpful in improving functional and neurological outcomes that are probably linked to its anti-inflammatory and antioxidant properties. Trial Registration. This trial is registered with IRCT20150629022965N17 at Iranian Registry of Clinical Trials (registration date: 25/07/2018).

The Influence of Periodontal Diseases and the Stimulation of Saliva Secretion on the Course of the Acute Phase of Ischemic Stroke.

Background and purpose: The course of an ischemic stroke depends on many factors. The influence of periodontal diseases and the stimulation of salivation on the course and severity of stroke remains unresolved. Therefore, the aim of the study was to analyze the severity of ischemic stroke depending on the occurrence of periodontal diseases and saliva stimulation. Methods: The severity of the neurological condition was assessed using the NIHSS scale on days one, three and seven of stroke. The incidence of periodontal diseases was classified using the Hall’s scale in the first day of stroke. On days one and seven of stroke, the concentration of IL-1β, MMP-8, OPG and RANKL in the patients’ saliva was assessed using the Elisa technique. At the same time, the level of CRP and the number of leukocytes in the peripheral blood were tested on days one, three and seven of the stroke, and the incidence of upper respiratory and urinary tract infections was assessed. Results:100 consecutive patients with their first ever ischemic stroke were enrolled in the study. 56 randomly selected patients were subjected to the stimulation of salivation, the remaining patients were not stimulated. In the study of the severity of the neurological condition using the NIHS scale on days three and seven of stroke, the degree of deficit in patients without periodontal disease significantly improved compared to patients with periodontal disease, respectively (p < 0.01 and p = 0.01). Patients from the stimulated group had more severe neurological deficit at baseline (p = 0.04). On days three and seven of neurological follow-up, the condition of patients from both groups improved with a further distinct advantage of the unstimulated group over the stimulated group, respectively (p = 0.03 and p < 0.001). In patients from both groups, a statistically significant decrease in CRP and lymphocyte levels was observed on day seven in relation to day one. Conclusions: The occurrence of periodontal disease in a patient with stroke affects the severity of stroke. Stimulation of the mouth and salivary glands in these patients may have a positive effect on the course of stroke, taking into account the dynamics of neurological symptoms.

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.

Serum TG/HDL-C level at the acute phase of ischemic stroke is associated with post-stroke cognitive impairment.

The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) bears a relation with poor outcomes of acute ischemic stroke (AIS), but the impact of serum TG/HDL-C level on post-stroke cognitive impairment (PSCI) remains unknown. We conducted this prospective study to explore the association between TG/HDL-C and PSCI. Consecutive AIS patients from the Stroke Units of our hospital were prospectively enrolled between July 1, 2020, and June 30, 2021. Blood samples were collected within 24h after admission. Cognition function was evaluated by the Montreal Cognitive Assessment (MoCA) at 3months after stroke. We used logistic regression analyses to explore the relationship between TG/HDL-C and PSCI, and then used a receiver operating characteristic (ROC) analysis to assess the ability of acute TG/HDL-C for predicting PSCI. A total of 227 AIS patients were recruited. Compared with patients without PSCI, those with PSCI had a higher level of TG/HDL-C at admission (P < 0.01). The multivariate logistic regression analyses showed that TG/HDL-C level was independently associated with PSCI (P < 0.01). The area under the curve of the ROC for TG/HDL-C as predictor of PSCI was 0.701 (95%CI 0.635-0.768). The optimal cutoff value of TG/HDL-C to indicate PSCI was 1.564, which gave a sensitivity of 55.2% and specificity of 80.6%. Our study demonstrated that a higher level of TG/HDL-C at the acute phase of ischemic stroke predicted the presence of PSCI at 3months after stroke.

A Review of the Role of Transthoracic and Transesophageal Echocardiography, Computed Tomography, and Magnetic Resonance Imaging in Cardioembolic Stroke.

Stroke is a major source of morbidity and mortality worldwide, accounting for the second largest cause of mortality and the third greatest cause of disability. Stroke is frequently preceded by a transient ischemic attack (TIA). The etiologies of 20–30% of ischemic strokes are unknown, and thus are termed “cryptogenic strokes”. About 25% of ischemic strokes are cardioembolic. Strokes occur at a rate of around 2% per year in individuals with heart failure with reduced ejection fraction (HFrEF), with a strong correlation between stroke risk and the degree of ventricular impairment. Furthermore, stroke risk is augmented in the absence of anticoagulation therapy. Cardioembolic strokes, when treated inadequately, have a greater predilection for recurrences than atherothrombotic strokes, both early and late in life. The role of a patent foramen ovale in strokes, specifically in “cryptogenic strokes”, is a matter of concern that deserves due attention. The use of tissue-engineered heart valves and aspirin for minimizing the risk of stroke is recommended.Transthoracic echocardiography (TTE) is advantageous for assessing heart function in the acute phase of ischemic stroke. Transesophageal echocardiography (TEE) is considered the criterion standard procedure for detecting LAA thrombi. Computed tomography (CT) scans are good imaging modalities for identifying and excluding bleeding. Magnetic resonance imaging (MRI) images are by far the most effective imaging technique available for assessing the brain parenchymal state.We conducted a thorough review of the literature on the use of imaging modalities, highlighting the important contribution of TTE, TEE, CT, and MRI in the evaluation of cardioembolic stroke.

TIME OF BLOOD PRESSURE IN TARGET RANGE IN ACUTE ISCHEMIC STROKE

Objective: The management and the prognostic role of blood pressure (BP) during the acute phase of acute ischemic stroke (AIS) still remain controversial. Time in target range (TTR) of BP was recently introduced and is suggested that reflects both patient’s mean BP levels and the magnitude of BP variability (BPV). The purpose of this study is to investigate the association of blood pressure TTR derived from 24-hour ambulatory BP monitoring (ABPM), during the acute phase of AIS, with the severity of stroke and its predictive value for the 3 months outcome. Design and method: A total of 228 AIS patients (175 without prior disability) underwent ABPM every 20 minutes within 48 hours from onset using an automated oscillometric device (TM 2430, A&amp;D Company Ltd). Clinical and laboratory findings were recorded. Mean BP parameters, BPV (standard deviation) and TTR for systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) were calculated. Endpoints were death and disability/death at 3 months. Results: A total of 14,942 BP measurements were recorded (~66 per AIS patient) within 72 hours of stroke onset. Patient’s 24-hour blood pressure TTR was 34.7 ± 29.9%, 64.3 ± 24.2% and 55.3 ± 29.4% for SBP, DBP and MAP respectively. TTR of DBP and MAP differed according to stroke severity with a “J’’ association in all AIS patents. In patients without prior hypertension, TTR was lower as stroke severity increased for both DBP (p = 0.031) and MAP (p = 0.016). In 175 patients without prior disability, increase in TTR of DBP and MAP associated significantly with a decreased risk of disability/death in the unadjusted and fully adjusted models (HR: 0.96, 95% CI: 0.95–0.98, p = 0.001 and HR: 0.97, 95% CI: 0.95–0.98, p = 0.001). Increase in SBP TTR was associated significantly with an increased risk of disability/death in fully adjusted model with the addition of mean SBP (HR: 1.03, 95% CI: 1.00–1.07, p = 0.047). Conclusions: TTR can be included for a more detailed description of BP course, according to stroke severity, and for the evaluation of BP predictive role, in addition to mean BP values, derived from ABPM during the acute phase of AIS.

Association between homocysteine levels in acute stroke and poststroke depression: A systematic review and meta-analysis.

BackgroundHomocysteine (Hcy) has been confirmed to be associated with depression, but its relationship with poststroke depression (PSD) remains controversial. So far, there is no meta‐analysis of the correlation between Hcy level in acute stroke and PSD.MethodsA systematic search of a sub‐database of studies reporting the level of Hcy in the acute phase of ischemic stroke and PSD as of November 2021 was performed. Data extraction was performed strictly according to the inclusion and exclusion criteria. All data were analyzed using STATA 11.0. The standardized root mean square difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables.ResultsA total of 11 studies were included in this study, including 2789 participants. The results of this meta‐analysis showed that admission the levels of Hcy were significantly higher in PSD survivors, compared to non‐PSD survivors (SMD = 0.37, 95%CI = 0.07–0.66, P ＜ .001). Subgroup analysis showed that survivors with PSD diagnosed more than 3 months after stroke had significantly different the levels of from non‐PSD survivors (6 months: SMD = 0.61, 95%CI = 0.40–0.82, 9 months: SMD = 1.00, 95%CI = 0.59–1.41).ConclusionThe level of Hcy in the acute phase of ischemic stroke is a risk factor for PSD.

The Unconventional Growth Factors Cerebral Dopamine Neurotrophic Factor and Mesencephalic Astrocyte-Derived Neurotrophic Factor Promote Post-ischemic Neurological Recovery, Perilesional Brain Remodeling, and Lesion-Remote Axonal Plasticity.

Considerable efforts are currently made to develop strategies that boost endogenous recovery once a stroke has occurred. Owing to their restorative properties, neurotrophic factors are attractive candidates that capitalize on endogenous response mechanisms. Non-conventional growth factors cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) promote neuronal survival and reduce neurological deficits in the acute phase of ischemic stroke in mice. Their effects on endogenous repair and recovery mechanisms in the stroke recovery phase were so far unknown. By intracerebroventricular delivery of CDNF or MANF starting 3days post-stroke (1µg/day for 28days via miniosmotic pumps), we show that delayed CDNF and MANF administration promoted functional neurological recovery assessed by a battery of behavioral tests, increased long-term neuronal survival, reduced delayed brain atrophy, glial scar formation, and, in case of CDNF but not MANF, increased endogenous neurogenesis in the perilesional brain tissue. Besides, CDNF and MANF administration increased long-distance outgrowth of terminal axons emanating from the contralesional pyramidal tract, which crossed the midline to innervate ipsilesional facial nucleus. This plasticity promoting effect was accompanied by downregulation of the axonal growth inhibitor versican and the guidance molecules ephrin B1 and B2 in the previously ischemic hemisphere at 14 dpi, which represents a sensitive time-point for axonal growth. CDNF and MANF reduced the expression of the proinflammatory cytokines IL1β and TNFα in both hemispheres. The effects of non-conventional growth factors in the ischemic brain should further be examined since they might help to identify targets for restorative stroke therapy.

Elevation of cardiac biomarkers in stroke is associated with pathological findings on cardiac MRI-results of the HEart and BRain interfaces in Acute Stroke study.

Cardiac biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT), are frequently elevated in ischemic stroke patients but the mechanisms underlying this elevation are insufficiently understood. We determined the presence of cardiac damage, assessed using cardiac magnetic resonance imaging (CMR), in stroke patients with elevated hs-cTnT and brain natriuretic peptide (BNP). This is a post hoc analysis of the prospective, investigator-initiated, cross-sectional HEart and BRain interfaces in Acute Stroke (HEBRAS) study. All patients underwent the measurement of hs-cTnT and BNP as well as gadolinium-enhanced CMR in the acute phase of ischemic stroke. We performed unadjusted and adjusted logistic regression models to assess the association between hs-cTnT and BNP elevation and the presence of pathological CMR findings. Two hundred and thirty-three stroke patients (median age 67 years, 33% female) were included, of whom 43 (21%) had elevated hs-cTnT and 109 (47%) had elevated BNP. Hundred of the 233 (43%) patients had pathological findings on CMR had focal fibrosis as detected by late-gadolinium enhancement (LGE) in 51 (23%), left-ventricular hypertrophy (LVH) in 38 (16%), reduced LVEF in 32 (14%), and left-atrial dilatation in 34 (15%). After adjustment for potential confounders, both hs-cTnT (adjOR 5.0 (95%CI 2.1-11.7), p < 0.001) and BNP (adjOR 4.1 (95%CI 2.3-7.3), p < 0.001) were significantly associated with pathological findings on CMR. Hs-cTnT was associated with LGE, LVEF, and LVH, whereas BNP was associated with left-atrial dilatation and LVEF, LVH. Elevated cardiac biomarkers in acute stroke including CMR are strongly associated with pathological findings on CMR. In acute stroke patients, the elevation of cardiac biomarkers may identify patients who require a more thorough cardiology work-up.

Cochrane Review on Endovascular Thrombectomy and Intra-Arterial Interventions for Acute Ischemic Stroke

Cochrane Review on Endovascular Thrombectomy and Intra-Arterial Interventions for Acute Ischemic Stroke

Single-Cell RNA-Sequencing Analyses Revealed Heterogeneity and Dynamic Changes of Metabolic Pathways in Astrocytes at the Acute Phase of Ischemic Stroke.

Astrocyte plays important roles in the pathogenesis of ischemic stroke and reperfusion injury. They intensively participate in the energy metabolism of the brain, while their heterogeneity and function after ischemic stroke remain controversial. By employing single-cell sequencing of mice cortex at 12 h after transient middle cerebral artery occlusion (tMCAO) and comparing with the similar published datasets of 24h after tMCAO, we uncover the cellular phenotypes and dynamic change of astrocytes at the acute phase of ischemic stroke. In this study, we separately identified 3 major subtypes of astrocytes at the 12 h-tMCAO-system and 24 h-tMCAO-system, indicated the significant differences in the expression of genes and metabolic pathways in the astrocytes between the two time nodes after ischemic stroke, and detected the major change in the energy metabolism. These results provided a comprehensive understanding of the characteristic changes of astrocytes after ischemic stroke and explored the potential astrocytic targets for neuroprotection.

Personalized Neurophysiological and Neuropsychological Assessment of Patients with Left and Right Hemispheric Damage in Acute Ischemic Stroke.

The leading factors of post-stroke disability are motor disorders and cognitive dysfunctions. The aim of the study was to identify and provide a rationale for the variable early cognitive dysfunction in right and left hemispheric damage in patients with acute stroke. The study included 80 patients diagnosed with ischemic stroke. All patients were assessed for cognitive status, depression, fatigue and anxiety. For objectification, the method of evoked potentials (P300) and neuroimaging were used. Our findings revealed distinguishing features of cognitive dysfunction and identified a combination of the most informative markers characteristic of right and left hemispheric damage in patients with acute ischemic stroke. In patients with damage to the left hemisphere, a predominance of dysregulation syndrome (decrease in executive function and attention) was revealed, accompanied by various disorders such as severe anxiety and fatigue. The causes of this cognitive dysfunction may be directly related to stroke (damage to subcortical structures), as well as to a preexisting reduction in higher mental functions associated with age and vascular conditions. Cognitive impairments in patients with lesions of the right hemisphere were characterized by polymorphism and observed in the mental praxis, speech (with predominant semantic component) and abstract thinking domains. They are closely linked to each other and are more related to the lateralization of the lesion and preexisting neurodegeneration than to the localization of the ischemic lesion. The study of P300-evoked potentials is a good tool for confirming cognitive dysfunction. The latent period of the P300 wave is more sensitive to neurodegeneration, while the amplitude factor characterizes vascular pathology to a greater extent. The results of the study provide a rationale for a comprehensive assessment of lateralization, stroke localization, underlying diseases, neurophysiological parameters and identified cognitive impairments when developing a plan of rehabilitation and neuropsychological measures aimed at cognitive and emotional recovery of patients both in the acute phase of ischemic stroke and when selecting further personalized rehabilitation programs.

Intravital Imaging Reveals the Ameliorating Effect of Colchicine in a Photothrombotic Stroke Model via Inhibition of Neutrophil Recruitment.

Although post-stroke neutrophil recruitment is known to be deleterious to neural tissues in the peri-infarct area, the precise behavior of recruited neutrophils remains elusive. In this study, potential therapeutic agents for modifying neutrophil behavior in the peri-infarct area were explored through intravital imaging of an experimental stroke mouse model. By applying in vivo 2-photon imaging to study a tightly controlled photothrombotic stroke mouse model, we established a highly sensitive and reproducible method for investigating the temporal dynamics of ischemic brain lesions. Taking advantage of this system, we revealed that neutrophil depletion by a neutrophil-specific antibody ameliorated the expansion of the infarct area, confirming the deleterious effect of neutrophils in the peri-infarct cortex. To identify neutrophil-targeted therapeutic approaches, we screened various agents and found that colchicine and an anti-P-selectin antibody were the most effective in inhibiting neutrophil attachment to the vessel wall in the early phase (6h post-infarction). Interestingly, further investigation in the later phase (16h post-infarction) revealed that colchicine potently inhibited neutrophil infiltration into the peri-infarct cortex; however, the anti-P-selectin antibody did not. Subsequent analysis revealed that the effect of the anti-P-selectin antibody against neutrophil attachment to the vessel wall was transient and thus insufficient for mitigating neutrophil infiltration. Finally, we revealed that colchicine treatment effectively ameliorated infarct expansion. In conclusion, we have established an intravital strategy to directly investigate pathophysiology in the ischemic border zone, and found that colchicine administration in the acute phase of ischemic stroke is a potential novel therapeutic strategy.

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats.

Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton’s jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats’ cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

Neuroprotective Effect of Physical Activity in Ischemic Stroke: Focus on the Neurovascular Unit.

Cerebral ischemia is one of the major diseases associated with death or disability among patients. To date, there is a lack of effective treatments, with the exception of thrombolytic therapy that can be administered during the acute phase of ischemic stroke. Cerebral ischemia can cause a variety of pathological changes, including microvascular basal membrane matrix, endothelial cell activation, and astrocyte adhesion, which may affect signal transduction between the microvessels and neurons. Therefore, researchers put forward the concept of neurovascular unit, including neurons, axons, astrocytes, microvasculature (including endothelial cells, basal membrane matrix, and pericyte), and oligodendrocytes. Numerous studies have demonstrated that exercise can produce protective effects in cerebral ischemia, and that exercise may protect the integrity of the blood-brain barrier, promote neovascularization, reduce neuronal apoptosis, and eventually lead to an improvement in neurological function after cerebral ischemia. In this review, we summarized the potential mechanisms on the effect of exercise on cerebral ischemia, by mainly focusing on the neurovascular unit, with the aim of providing a novel therapeutic strategy for future treatment of cerebral ischemia.

Platelet-Derived Drug Targets and Biomarkers of Ischemic Stroke-The First Dynamic Human LC-MS Proteomic Study.

(1) Objective: The aim of this dynamic LC-MS (liquid chromatography and mass spectrometry) human platelet proteomic study was to identify the potential proteins candidates for biomarkers of acute ischemic stroke (AIS), their changes during the acute phase of stroke and to define potential novel drug targets. (2) Methods: A total of 32 patients (18–80 years old) were investigated that presented symptoms of AIS lasting less than 24 h from the onset, confirmed by neurological examination and/or new cerebral ischemia visualized in the CT (computed-tomography) scans. The analysis of platelet proteome was performed using LC-MS at baseline, and then on the third and seventh day from the onset of symptoms. The control group was demographically matched without any clinical signs of acute brain injury. (3) Results: The differences between platelets, at 24 h after first symptoms of stroke subjects and the control group included: β-amyloid A4 and amyloid-like protein 2, coactosin-like protein, thymidine phosphorylase 4 (TYMP-4), interferon regulatory factor 7 (IRF7), vitamin K-dependent protein S, histone proteins (H2A type 1 and 1-A, H2A types 2B and J, H2Av, -z, and -x), and platelet basic protein. The dynamic changes in the platelet protein concentration involved thrombospondin-1, thrombospondin-2, filamin A, B, and C. (4) Conclusions: This is the first human dynamic LC-MS proteomic study that differentiates platelet proteome in the acute phase of ischemic stroke in time series and compares the results with healthy controls. Identified proteins may be considered as future markers of ischemic stroke or therapeutic drug targets. Thymidine phosphorylase 4 (TYMP-4) holds promise as an interesting drug target in the management or prevention of ischemic stroke.