New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases.

Johannes Boltze,Inga K Koerte,Farida Sohrabji,R Anne Stetler,Gerlinde A S Metz,Karim Fouad,Dandan Sun,Fudong Liu,Denis Vivien,Marion S Buckwalter,Wolfgang Härtig,Ye Xiong,Friedhelm C Hummel,Marietta Zille,Peter Ludewig,Anna M Planas,Piotr Walczak,Karen Gertz,Nadine Didwischus,Nikolaus Plesnila,Daniel F Hanley,Saravanan S Karuppagounder,Charlotte J Stagg,Kunjan R Dave,Richard F Keep,Axel Montagne,Ami P Raval,Raghu Vemuganti,Zaal Kokaia,Maulana Ikhsan,Jukka Jolkkonen,Ann M Stowe,Michael Chopp,Thorsten R Doeppner,Jens P Dreier,Rick M Dijkhuizen,Akihiko Taguchi,Peiying Li,Mathias Gelderblom,Alex Palumbo,Jian Wang,Miguel A Pérez-Pinzón ,Sabine Ulrike Vay ,Ignacio Lizasoaín ,Édith Hamel ,Dominika Gołubczyk ,Mirosław Janowski ,Barbara Gregson ,Monica S Pearl ,Mickaël Tanter ,Jérôme Badaut ,André Obenaus ,Lauren Sansing ,Maria Adele Rueger ,Jaroslaw Aronowski ,Matteo Caleo

doi:10.3389/fnagi.2021.623751

Abstract

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

Highlights

Overcoming more than two decades of translational standstill and providing options to treat selected stroke patients in extended time windows, the advent of recanalization approaches has sparked a new dynamic in preclinical and clinical stroke research
Macrophages and microglia undergo acute activation during the first week after intracerebral hemorrhage (ICH), with microglia producing inflammatory cytokines and chemokines, and a decreasing expression of microglia-specific genes (Taylor et al, 2017). Other immune cells such as neutrophils are another source of damage and secondary injury as they infiltrate the brain in response to sterile inflammation triggered by ischemic stroke or ICH
Based on the setbacks seen in the past decades of cerebrovascular disease research, the field has clearly consolidated and recognized the reasons for previous translational failure as exemplified in the field of cell therapies (Cui et al, 2019)

Summary

Introduction

Overcoming more than two decades of translational standstill and providing options to treat selected stroke patients in extended time windows, the advent of recanalization approaches has sparked a new dynamic in preclinical and clinical stroke research. FS (Bryan, TX, USA) showed that anti-inflammatory miRNA therapy improves long-term affective dysfunction after ischemic stroke (Panta et al, 2019).

Results

Conclusion