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Filling the gaps on stroke research: Focus on inflammation and immunity.
Levard, Damien; Buendia, Izaskun; Lanquetin, Anastasia; Glavan, Martina; Vivien, Denis; Rubio, Marina.
  • Levard D; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France.
  • Buendia I; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France.
  • Lanquetin A; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France.
  • Glavan M; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France.
  • Vivien D; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France; CHU Caen, Department of Clinical Research, Caen University Hospital, Avenue de la Côte de Nacre, Caen, France.
  • Rubio M; Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Caen, France. Electronic address: rubio@cyceron.fr.
Brain Behav Immun ; 91: 649-667, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064858
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ABSTRACT
For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stroke / Stroke Rehabilitation Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Brain Behav Immun Journal subject: Allergy and Immunology / Brain / Psychophysiology Year: 2021 Document Type: Article Affiliation country: J.bbi.2020.09.025

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stroke / Stroke Rehabilitation Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: Brain Behav Immun Journal subject: Allergy and Immunology / Brain / Psychophysiology Year: 2021 Document Type: Article Affiliation country: J.bbi.2020.09.025