The meningeal and choroidal infiltration routes for leukocytes in stroke

Yeah, translating experimental research into practice is hard. Leaders tackle such hard problems. They don't throw up their hands in defeat. Whom the hell is going to solve this neuronal cascade of death? Way back in March 2006 this was already known. So 12 years and we have NO progress. I see nothing in the future unless we get stroke survivors running stroke research by following an actual strategy.  Stop using neuroprotection instead of the neuronal cascade of death. Neuroprotection gives NO sense of urgency.

1,026 failed experimental treatments in acute stroke

Corinne Benakis, Gemma Llovera, Arthur Liesz

First Published June 18, 2018 Review Article

https://doi.org/10.1177/1756286418783708

Article information

Abstract

Stroke is a major health burden as it is a leading cause of morbidity and mortality worldwide. Blood flow restoration, through thrombolysis or endovascular thrombectomy, is the only effective treatment but is restricted to a limited proportion of patients due to time window constraint and accessibility to technology. Over the past two decades, research has investigated the basic mechanisms that lead to neuronal death following cerebral ischemia. However, the use of neuroprotective paradigms in stroke has been marked by failure in translation from experimental research to clinical practice. In the past few years, much attention has focused on the immune response to acute cerebral ischemia as a major factor to the development of brain lesions and neurological deficits. Key inflammatory processes after stroke include the activation of resident glial cells as well as the invasion of circulating leukocytes. Recent research on anti-inflammatory strategies for stroke has focused on limiting the transendothelial migration of peripheral immune cells from the compromised vasculature into the brain parenchyma. However, recent trials testing the blockage of cerebral leukocyte infiltration in patients reported inconsistent results. This emphasizes the need to better scrutinize how immune cells are regulated at the blood–brain interface and enter the brain parenchyma, and particularly to also consider alternative cerebral infiltration routes for leukocytes, including the meninges and the choroid plexus. Understanding how immune cells migrate to the brain via these alternative pathways has the potential to develop more effective approaches for anti-inflammatory stroke therapies.