During an ischaemic stroke, a blockage cuts off blood supply to parts of the brain. However, the damage to the brain does not stop immediately. Waves of disrupted electrical activity, known as cortical spreading depolarisations (CSDs), travel through the injured brain and can cause additional harm. Until now, it has been difficult to measure these signals accurately, because existing technologies poorly capture the very slow brain activity (electrical) changes involved.

A team of researchers from the University of Manchester, the Institute of Microelectronics of Barcelona (IMB-CNM, CSIC), and ICN2, together with their industry partner, MultiChannel Systems in Germany, has developed a technology that can monitor these signals and identify areas of the brain at greater risk of damage. Their research has been published in Brain.

Using highly sensitive graphene transistor-based neural interfaces, researchers were able to record these slow and low frequency electrical waves in unprecedented detail. They discovered that the shape of the electrical signals revealed important information about the health of the surrounding brain tissue. The signals could distinguish between tissue that was relatively healthy, tissue that was at risk, and tissue that was already severely compromised. These tests were performed in mice.

Researchers also learnt that these signals could predict how blood flow would respond to the electrical wave. In healthier tissue, blood flow increased to help the brain recover from the event, whereas in vulnerable tissue blood flow could further decrease, worsening the injury.

Could ketamine be used as a potential treatment?

Importantly, the study also showed that these harmful responses could be altered using a low dose of ketamine, a drug already used clinically. Ketamine reduced the duration of the damaging electrical waves, shifted the associated blood flow response from potentially harmful vasoconstriction towards vasodilation, and reduced the overall area of brain damage. These findings reveal one potential mechanism that may contribute to the neuroprotective effects of ketamine following stroke.

The findings suggest that graphene-based brain monitoring could one day provide clinicians with a real-time window of how the injured brain tissue recovers after a stroke event. This could help identify patients at greatest risk of further tissue damage and support the development of new treatments aimed at protecting the brain and improving recovery.

A consolidated collaboration

The study involved two ICN2 groups: the Advanced Electronic Materials and Devices Group (ICREA Prof. Jose A. Garrido, Dr Elena del Corro, and Dr Eduard Masvidal) and the Nanomedicine Lab (ICREA Prof. Kostas Kostarelos).

This advance marks a new milestone in the long-standing collaboration between IMB-CNM, the University of Manchester and ICN2, which began with the development of graphene microtransistor technology for recording ultraslow brain signals, first published in Nature Materials in 2018.

Since then, the teams have continued to develop graphene-based technologies for neural interfaces, advancing both the recording of brain signals across a wide range of frequencies and devices capable of combining neural recording and stimulation, with studies published in Nature Nanotechnology and, more recently, in Nature Communications. These technologies are developed and validated in collaboration with specialised research groups to explore their application beyond the laboratory.

Reference article:

Flaherty, S. M.; Eladly, A.; Hills, K.; Merlini, J.; Fernandes, L. F.; Masvidal-Codina, E.; Illa, X.; Prats-Alfonso, E.; Del Corro, E.; Garrido, J. A.; Meents, J.; Jeschke, C.; Mohrlok, R.; Kostarelos, K.; Allan, S. M.; Guimerà-Brunet, A.; Wykes, R. C. Perfusion-dependent spreading depolarization signatures identify tissue vulnerability in stroke. Brain. (2026). https://doi.org/10.1093/brain/awag305.