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Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

ABSTRACT: Background and Purpose: Stroke induces immediate profound alterations of the peripheral immune system rendering patients more susceptible to post-stroke infections. The precise mechanisms maintaining stroke-induced immune alterations (SIIA) remain unknown. High-Mobility-Group-Protein B1 (HMGB-1) is elevated for at least 7 days post-stroke and has been suggested to mediate SIIA. Patients with rapid clinical recovery of neurological deficits rarely develop severe infections. We therefore investigated whether rapid neurological recovery (either spontaneous or secondary to neurovascular recanalization therapy) alters the course of SIIA. National Institutes of Health Stroke Scale (NIHSS) served as surrogate marker for neurological improvement. Methods: Fluorescence-activated cell sorting was used to define leukocyte subpopulations. C-reactive protein (CRP), procalcitonin (PCT), HMGB-1, GM-CSF; IFN-?, IFN-?, IL-1?, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, IL-17F, IL-18, TNF-?, MIF, IL-8, MCP-1, MCP-4, MIP-3?, MIP-3?, Eotaxin, soluble IL-6 receptor, E-selectin, and P-selectin were analyzed by ELISA or Multiplex Assays. Serum miRNA expression changes were analyzed by qPCR. Results: Cellular parameters were similar in the improved and non-improved cohort on admission. In patients with rapid clinical recovery absolute and relative leukocyte, neutrophil, and lymphocyte numbers normalized promptly overnight. In contrast, HMGB-1 serum levels did not differ between the two groups. Nine miRNA were found to be differentially expressed between improved and non-improved patients. Conclusions: SIIA are detectable on admission of acute stroke patients. While it was assumed that post-stroke immunosuppression is rapidly reversed with improvement this is the first data set that shows that improvement actually is associated with a rapid reversal of SIIA demonstrating that SIIA require a constant signal to persist. The observation that HMGB-1 serum concentrations were similar in improved and non-improved cohorts argues against a role for this pro-inflammatory mediator in the maintenance of SIIA. Serum miRNA observed to be regulated in stroke in other publications was counter regulated with improvement in our cohort.

SUBMITTER: Vogelgesang A

PROVIDER: S-EPMC6504832 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

Vogelgesang Antje A Witt Carl C Heuer Christin C Schulze Juliane J Gellrich Juliane J von Sarnowski Bettina B Langner Sönke S Dressel Alexander A Ruhnau Johanna J

Frontiers in neurology 20190501

<b>Background and Purpose:</b> Stroke induces immediate profound alterations of the peripheral immune system rendering patients more susceptible to post-stroke infections. The precise mechanisms maintaining stroke-induced immune alterations (SIIA) remain unknown. High-Mobility-Group-Protein B1 (HMGB-1) is elevated for at least 7 days post-stroke and has been suggested to mediate SIIA. Patients with rapid clinical recovery of neurological deficits rarely develop severe infections. We therefore in ...[more]

PMID: 31118917

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Project description:Background: Granulocytes and monocytes are the first cells to invade the brain post stroke and are also being discussed as important cells in early neuroinflammation after seizures. We aimed at understanding disease specific and common pathways of brain-immune-endocrine-interactions and compared immune alterations induced by stroke and seizures. Therefore, we compared granulocytic and monocytic subtypes between diseases and investigated inflammatory mediators. We additionally investigated if seizure type determines immunologic alterations. Material and Methods: We included 31 patients with acute seizures, 17 with acute stroke and two control cohorts. Immune cells were characterized by flow cytometry from blood samples obtained on admission to the hospital and the following morning. (i) Monocytes subpopulations were defined as classical (CD14++CD16-), (ii) intermediate (CD14++CD16+), and (iii) non-classical monocytes (CD14dimCD16+), while granulocyte subsets were characterized as (i) "classical granulocytes" (CD16++CD62L+), (ii) pro-inflammatory (CD16dimCD62L+), and (iii) anti-inflammatory granulocytes (CD16++CD62L-). Stroke patient's blood was additionally drawn on days 3 and 5. Cerebrospinal fluid mitochondrial DNA was quantified by real-time PCR. Plasma High-Mobility-Group-Protein-B1, metanephrine, and normetanephrine were measured by ELISA. Results: HLA-DR expression on monocytes and their subpopulations (classical, intermediate, and non-classical monocytes) was reduced after stroke or seizures. Expression of CD32 was increased on monocytes and subtypes in epilepsy patients, partly similar to stroke. CD32 and CD11b regulation on granulocytes and subpopulations (classical, anti-inflammatory, pro-inflammatory granulocytes) was more pronounced after stroke compared to seizures. On admission, normetanephrine was upregulated in seizures, arguing for the sympathetic nervous system as inducer of immune alterations similar to stroke. Compared to partial seizures, immunologic changes were more pronounced in generalized tonic-clonic seizures. Conclusion: Seizures lead to immune alterations within the immediate postictal period similar but not identical to stroke. The type of seizures determines the extent of immune alterations.

Project description:Objective: Post-stroke epilepsy (PSE) is associated with increased morbidity and mortality. Stroke-associated acute symptomatic seizures are an important risk factor: 20.8-34.3% of these patients will go on to develop PSE. Identifying these "high risk" individuals may result in earlier PSE diagnosis, treatment, and avoidance of seizure-related morbidity. This study was to identify predictors of PSE development in patients with stroke-associated acute symptomatic seizures. Participants and Methods: This was a retrospective cohort study of 167 patients with stroke-associated acute symptomatic seizures admitted to the Neurology Department of a tertiary Hospital of China, from 1 May 2006 to 30 January 2020. Both those with primary ischemic stroke and intracerebral hemorrhage were included in the study. Patient demographics, medical history, stroke-associated, and seizure-related variables were evaluated with univariable analysis and multivariable Cox regression analysis. PSE was defined as unprovoked seizures occurring > 7 days post-stroke. Data points were extracted from medical records and supplemented by tele-interview. Results: Of the 167 patients with stroke-associated acute symptomatic seizures, 49 (29.3%) developed PSE. NIHSS score > 14 [hazard ratio (HR) 2.98, 95% CI 1.57-5.67], longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke) (HR 2.51, 95% CI 1.37-4.59) and multiple acute symptomatic seizures (HR 5.08, 95% CI 2.58-9.99) were independently associated with PSE development. This association remained in the sub-analysis within the ischemic stroke cohort. In the sub-analysis of the hemorrhagic stroke cohort, multilobar involvement (HR 4.80, 95% CI 1.49-15.39) was also independently associated with development of PSE. Further, we developed a nomogram to predict individual risk of developing PSE following stroke-associated acute symptomatic seizures. The nomogram showed a C-index of 0.73. Conclusion: More severe neurofunctional deficits (NIHSS score > 14), longer interval from stroke to acute symptomatic seizures (days 4-7 post-stroke), and multiple acute symptomatic seizures were independently associated with development of PSE in patients with stroke-associated acute symptomatic seizures. This knowledge may increase clinical vigilance for development of PSE, facilitating rapid diagnosis and treatment initiation, and subsequently reduce seizure-related morbidity.

Project description:Background: Research over the last two decades has highlighted the critical role of Brain-derived neurotrophic factor (BDNF) in brain neuroplasticity. Studies suggest that physical exercise may have a positive impact on the release of BDNF and therefore, brain plasticity. These results in animal and human studies have potential implications for the recovery from damage to the brain and for interventions that aim to facilitate neuroplasticity and, therefore, the rehabilitation process. Purpose: The aim of this study was to carry out a systematic review of the literature investigating how aerobic exercises and functional task training influence BDNF concentrations post-stroke in humans and animal models. Data Sources: Searches were conducted in PubMed (via National Library of Medicine), SCOPUS (Elsevier), CINAHL with Full Text (EBSCO), MEDLINE 1946-present with daily updates (Ovid) and Cochrane. Study Selection: All of the database searches were limited to the period from January, 2004 to May, 2017. Data Extraction: Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the ARRIVE Guidelines, and the study that evaluated human BDNF was assessed using the PEDro Scale. Data Synthesis: Twenty-one articles were included in this review. BDNF measurements were performed systemically (serum/plasma) or locally (central nervous system). Only one study evaluated human BDNF concentrations following physical exercise, while 20 studies were experimental studies using a stroke model in animals. A wide variation was observed in the training protocol between studies, although treadmill walking was the most common type of intervention among the studies. Studies were of variable quality: the studies that used animal models scored from 8/20 to 15/20 according to the ARRIVE Guidelines. The only study that evaluated human subjects scored 5/10 according to the PEDro scale and, which indicates a quality classified as "fair". Conclusions: The results of the current systematic review suggest that aerobic exercise promotes changes in central BDNF concentrations post-stroke. On the other hand, BDNF responses following functional exercises, such as reaching training and Constraint Induced Movement Therapy (CIMT), seem to be still controversial. Given the lack of studies evaluating post-stroke BDNF concentration following physical exercise in humans, these conclusions are based on animal work.

Dataset Information

Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

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Clinical Improvement Following Stroke Promptly Reverses Post-stroke Cellular Immune Alterations.

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