Regulation of therapeutic hypothermia on inflammatory cytokines, microglia polarization, migration and functional recovery after ischemic stroke in mice

Abstract BackgroundIncreasing evidence suggests that microglia experience two distinct phenotypes after acute ischemic stroke (AIS): a deleterious M1 phenotype and a neuroprotective M2 phenotype. Promoting the phenotype shift of M1 microglia to M2 microglia is thought to improve functional recovery after AIS. Minocycline, a tetracycline antibiotic, can improve functional recovery after cerebral ischemia in pre-clinical and clinical research. However, the role and mechanisms of minocycline in microglia polarization is unclear.MethodsUsing the transient middle cerebral artery occlusion - reperfusion (MCAO/R) model, we treated mice with saline or different minocycline concentration (10, 25, or 50 mg/kg, i.p., daily for 2 wk) at 24 h after reperfusion. Neurobehavioral evaluation, rotarod test, and corner turning test were carried out on day 14 after reperfusion. Then, neuronal injury, reactive gliosis, and microglia polarization were performed on day 7 following MCAO/R. Finally, we treated primary microglial cultures with LPS (Lipopolysaccharide; 100 ng/mL) plus IFN-γ (20 ng/mL) 24 h to induce M1 phenotype and observed the effects of minocycline on the M1/M2-related mRNAs and the STAT1/STAT6 pathway.ResultsWe found that a 14-day treatment with minocycline increased the survival rate and promoted functional outcomes evaluated with neurobehavioral evaluation, rotarod test, and corner turning test. Meanwhile, minocycline reduced the brain infarct volume, alleviated neuronal injury, and suppressed reactive gliosis on day 7 following MCAO/R. Moreover, we observed an additive effect of minocycline on microglia polarization to the M1 and M2 phenotypes in vivo and in vitro. In the primary microglia, we further found that minocycline prevented neurons from OGD/R-induced cell death in neuron-microglia co-cultures via regulating M1/M2 microglia polarization through the STAT1/STAT6 pathway. ConclusionMinocycline promoted microglial M2 polarization and inhibited M1 polarization, leading to neuronal survival and neurological functional recovery. The findings deepen our understanding of the mechanisms underlying minocycline-mediated neuroprotection in AIS.

Download Full-text

The relationship of leukoaraiosis severity and the degree of functional recovery after atherothrombotic ischemic stroke

Ukrainian Neurological Journal ◽

10.30978/unj2020-1-28 ◽

2020 ◽

Vol 0 (1—2) ◽

pp. 28-33

Author(s):

L. V. Panteleienko

Keyword(s):

Ischemic Stroke ◽

Functional Recovery ◽

Relationship Of ◽

The Relationship

Download Full-text

Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

International Journal of Molecular Sciences ◽

10.3390/ijms22084207 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4207

Author(s):

Nikola Tułowiecka ◽

Dariusz Kotlęga ◽

Andrzej Bohatyrewicz ◽

Małgorzata Szczuko

Keyword(s):

Ischemic Stroke ◽

Cardiovascular Diseases ◽

Blood Brain Barrier ◽

Inflammatory Cytokines ◽

The Body ◽

Brain Barrier ◽

Lipoxin A4 ◽

Stroke Treatment ◽

Blood Brain ◽

Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

Download Full-text

Role of S100β Glial Protein as a Serological Marker for Analysis of Acute Ischemic Stroke

Journal of Stroke Medicine ◽

10.1177/25166085211011284 ◽

2021 ◽

pp. 251660852110112

Author(s):

Kiran Buddharaju ◽

Mahendra Javali ◽

Anish Mehta ◽

R Srinivasa ◽

Purushottam Acharya

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Recovery ◽

Protein Level ◽

Serological Marker ◽

Protein Levels ◽

S100β Protein ◽

Asymptomatic Volunteers ◽

Scale Scores

Background: Stroke is a major cause of neurological disability, which can be often predicted with serological markers. Glial-derived S100β protein is a potential biomarker for cerebral ischemia and may be helpful in predicting the severity, outcome, and recovery of stroke. Aim: This study aimed to study the role of S100β glial protein as a serological marker in predicting the severity of acute ischemic stroke (AIS), outcome, and functional recovery after 1 month. Methods: A hospital-based prospective case control study included 43 consecutive patients, >18 years old, who were admitted with acute middle cerebral artery (MCA) territory infarcts within 72 h of onset of neurological deficits. Control group comprised of 43 age-matched asymptomatic volunteers. Independent t-test and chi square test were used to compare the means and evaluate the association between protein level and various parameters. P ≤ .05 was statistically significant. Results: S100β protein level in AIS patients was significantly higher compared to controls ( P < .05). Elevated serum S100β protein level was found to be associated with larger infarct volumes, higher National Institute Health Stroke Scale scores, and higher modified Rankin Scale scores at admission ( P < .05). Patients with higher S100β protein levels at admission had poor recovery at 1 month compared to patients having normal S100β protein levels. Conclusion: S100β protein levels at admission after an acute MCA territory infarct may be used as a reliable serological tool in predicting the severity, outcome, and functional recovery in stroke.

Download Full-text

Acute Ischemic Stroke is Associated with Increased Serum Levels of Pro-inflammatory Cytokines

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-020-00892-8 ◽

2020 ◽

Author(s):

Bhagirath Ramawat ◽

Alvee Saluja ◽

Jayashree Bhatacharjee ◽

Anshuman Srivastava ◽

Rajinder K. Dhamija

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Inflammatory Cytokines ◽

Serum Levels ◽

Pro Inflammatory Cytokines

Download Full-text

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2008.08.080 ◽

2008 ◽

Vol 41 (16-17) ◽

pp. 1330-1334 ◽

Cited By ~ 65

Author(s):

Vanja Basic Kes ◽

Ana-Maria Simundic ◽

Nora Nikolac ◽

Elizabeta Topic ◽

Vida Demarin

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Inflammatory Cytokines ◽

Neurological Deficit ◽

Stroke Outcome ◽

Anti Inflammatory

Download Full-text

Circulating long noncoding RNA ANRIL downregulation correlates with increased risk, higher disease severity and elevated pro-inflammatory cytokines in patients with acute ischemic stroke

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.22629 ◽

2018 ◽

Vol 33 (1) ◽

pp. e22629 ◽

Cited By ~ 16

Author(s):

Lijuan Feng ◽

Jun Guo ◽

Fen Ai

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Disease Severity ◽

Inflammatory Cytokines ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Increased Risk ◽

Pro Inflammatory Cytokines

Download Full-text

Impact of Post-Stroke Recanalization on General and Upper Limb Functioning: A Prospective, Observational Study

Neurology International ◽

10.3390/neurolint13010005 ◽

2021 ◽

Vol 13 (1) ◽

pp. 46-58

Author(s):

João Paulo Branco ◽

Filipa Rocha ◽

João Sargento-Freitas ◽

Gustavo C. Santo ◽

António Freire ◽

...

Keyword(s):

Ischemic Stroke ◽

Observational Study ◽

Acute Ischemic Stroke ◽

Upper Limb ◽

Functional Recovery ◽

Prospective Observational Study ◽

Positive Impact ◽

Rehabilitation Program ◽

Patient Functioning ◽

The Impact

The objective of this study is to assess the impact of recanalization (spontaneous and therapeutic) on upper limb functioning and general patient functioning after stroke. This is a prospective, observational study of patients hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery (n = 98). Patients completed a comprehensive rehabilitation program and were followed-up for 24 weeks. The impact of recanalization on patient functioning was evaluated using the modified Rankin Scale (mRS) and Stroke Upper Limb Capacity Scale (SULCS). General and upper limb functioning improved markedly in the first three weeks after stroke. Age, gender, and National Institutes of Health Stroke Scale (NIHSS) score at admission were associated with general and upper limb functioning at 12 weeks. Successful recanalization was associated with better functioning. Among patients who underwent therapeutic recanalization, NIHSS scores ≥16.5 indicate lower general functioning at 12 weeks (sensibility = 72.4%; specificity = 78.6%) and NIHSS scores ≥13.5 indicate no hand functioning at 12 weeks (sensibility = 83.8%; specificity = 76.5%). Recanalization, either spontaneous or therapeutic, has a positive impact on patient functioning after acute ischemic stroke. Functional recovery occurs mostly within the first 12 weeks after stroke, with greater functional gains among patients with successful recanalization. Higher NIHSS scores at admission are associated with worse functional recovery.

Download Full-text