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Neuroprotective peptides against stroke

Scientists at the CSIC have developed a neuroprotective peptide which can be useful in the treatment and prevention of stroke or cerebral ischemia and other situations that cause brain damage. In vitro experiments have shown its efficacy when used on cultured neurons. Partners interested in licensing the patent are sought.

Cultured neuronal cells obtained by the scientists at the IBB. To fight brain injury after a stroke is to fight against time. One of the main problems in current standard treatment, the thrombolytic therapy, is the limited available time in which this therapy can be effective. That’s why it has to be applied not later than three or four hours after the stroke. Also, thrombolytic therapies have adverse effects and they cannot always be used –for instance, they are not suitable in cases of hemorrhagic strokes- which leaves many patients without available treatment. Therefore, there is a high interest in developing alternative treatments.


A scientific team led by Margarita-Díaz Guerra, at the Instituto de Investigaciones Biomédicas (joint centre CSIC-Universidad Autónoma de Madrid), has developed peptides that can be useful in the treatment and prevention of strokes, neuronal injury due to the lack of neurotrophic support, hypoxia, neuronal disconnection or mechanical damage after traumatic brain or spinal injury, and neurodegenerative disorders.

Experiments on cultured neurons have shown that applying these peptides can protect neuronal cells that suffer excitotoxic conditions, which occurs  when there is an excessive activation of neuronal glutamate receptors. In the case of stroke, this process of excitotoxicity has a central role in the neuronal death.

Scientists have simulated the excitotoxic conditions in cultured neuronal cells by adding high amounts of a glutamate analogue. This causes the overactivation of the glutamate receptors and, consequently, progressive neuronal death in a period of time no longer than 24 hours. However, as scientists have demonstrated seen, applying these new peptides can decrease reduce this damage.

Margarita Díaz-Guerra explains that “the patented peptide acts over the neurotrophine receptor TrkB, although we have also developed other peptides with different targets, either related to TrKB or the glutamate receptors”.

“We don’t want to focus on just one strategy”, points out Díaz-Guerra. “When a neuron dies after a stroke, different cascades of mechanisms are triggered that will negatively affect pathways essential for neuronal survival.

Additionally, these mechanisms are transmitted from the brain region initially affected to the neighbouring zones. It is like an expansive wave that spreads neuronal damage. So, the issue is to try different strategies to block these mechanisms that disable the neuronal survival pathways and to stop this cascades of damage. It is also necessary to find out if these treatments can be an alternative or a complement to the standard thrombolytic therapy”.

The goal of these molecules is to avoid the secondary neuronal death after a stroke. Also, some preventive uses, such as surgery procedures whith a high risk of post-surgery ischemia.

Preventing neuronal secondary damage

Therefore, the goal of this kind of molecules is to avoid the secondary damage of neurons. It is hard to predict a stroke. It is also difficult to prevent the primary neuronal damage that affects the infarct core zone, where the blood supply reduction is stronger and the damage irreversible. But it would be possible to act on the area surrounding the infarct core, the so called “penumbra” which is functionally silent but structurally viable.

Nevertheless, if the blood supply is not restored in a short period of time, this penumbra area can suffer secondary neuronal death, unless suitable drugs are available. In this case, it would be possible to preserve these neurons before the lethal cascade of effects affects them.

Although the drug is still in a preliminary research stage, scientists are thinking about some potential applications in stroke prevention, for example in situations where the ischemic process is likely to happen. “That would be the case of open-heart surgery or endovascular surgery for aneurysm repair, procedures where there is a high risk for the patient of suffering post-surgery ischemic processes”, says Margarita Diaz-Guerra.


Eva Gabaldón Sahuquillo
Vicepresidencia Adjunta
de Transferencia de Conocimiento (CSIC)

Tel.: + 34 – 91 568 15 50
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