Why do we say ‘neuroprotection’ in stroke when we mean ‘brain protection or cerebroprotection’?

We read with great interest the paper by Norrving et al., Action Plan for Stroke in Europe 2018–2030, recently published in European Stroke Journal. ¹ The authors includes two additional domains, on primary prevention and life after stroke, along with research and development priorities for translational stroke research.

In this interesting manuscript, in the ‘Protective drugs for treatment and prevention’ section, specifically in ‘Neuroprotection’ subsection, the authors comment that

The concept of neuroprotection has evolved because protection is needed for functional units composed of neurons, glial cells, pericytes, macrophages and the vasculature. Approaches to protecting the white matter, which is under-represented in most animal models of stroke, need further development.

These ideas are in line with a review ² previously published, and therefore we would like to share ideas on why it would be important to avoid the term ‘neuroprotection’ in stroke and use ‘brain protection or cerebroprotection’ instead. By using this term, we avoid the mistake of driving therapies to protect specific cells (neurons) instead of protecting the whole organ (the brain). ³ Focal cerebral ischemia induces a complex series of mechanisms that damage brain cells, and brain tissue responds to noxious signals by inducing protective mechanisms. After a stroke, as the authors comment, not only neurons are vulnerable and responsible for functional damage; astrocytes, oligodendrocytes, microglia, perycites, endothelial, ependymal and immune cells are also relevant. In fact, in order to achieve global protection of the whole organ, it would not be enough to just protect each of these elements from the neurovascular unit, white matter fibre tracts (axon and myelin) and connectivity are also part of the brain.

In stroke studies, several drugs have been analysed that aimed to exert ‘neuroprotective’ effects. However, none of the ‘neuroprotectants’ available have effects exclusively on neurons, such as Ca²⁺and Na⁺channel inhibitors, glutamate antagonists, GABA agonists or 5HT agonists. Why do we then call them neuroprotectants?

Due to the failure of neuroprotective therapies in the past, it was thought that there was a poor connection between experimental animal models and stroke in patients and that translation was impeded. However, most concepts in stroke research (e.g. penumbra, tissue at risk, thrombolysis and reperfusion, time window, peri-infarct depolarisations, exofocal lesions, post-stroke depression) serve as examples of successful bench-to-bedside translation. ⁴ What are we doing wrong in neuroprotection?

Considering these observations and according to the authors of this manuscript, ¹ a global and integrated perspective of the brain seems more appropriate. Neuroprotection is just one piece of the pie, and therefore it would be better for researchers to use the term brain protection or cerebroprotection. ‘The way we think is determined by the way we speak’. ⁵