In just six months, the University of Szeged’s Cerebral Blood Flow and Metabolism Research Group has achieved a remarkable feat: having two scientific articles published in the prestigious Journal of Cerebral Blood Flow & Metabolism, with both papers featured on the journal’s cover. Prof. Dr. Eszter Farkas, head of the research group based at the Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi Medical School, and the Faculty of Science and Informatics, points out that both studies examine the critical connection between cortical spreading depolarization and key pathophysiological mechanisms of stroke.
The Cerebral Blood Flow and Metabolism Research Group at the University of Szeged has had two of its studies featured on the cover of the prestigious Journal of Cerebral Blood Flow & Metabolism in quick succession.
In its October 2024 issue, the D1-category journal – renowned for its focus on cerebral physiology and vascular research – featured an image from a study investigating the role of cortical spreading depolarization in post-stroke reperfusion failure. The paper’s first author, Dr. Anna Törteli, recently defended her PhD on the subject, while Dr. Ákos Menyhárt, assistant professor, and Prof. Dr. Eszter Farkas, head of the research group, served as corresponding and senior authors, respectively.
Prof. Dr. Eszter Farkas, head of the Cerebral Blood Flow and Metabolism Research Group of the University of Szeged
Photo by Ádám Kovács-Jerney
A few months later, the cover of the February 2025 issue highlighted a figure from a review article by Prof. Dr. Eszter Farkas and her German colleague, Prof. Dr. Christine Rose, illustrating the connection between acidification in brain tissue – technically referred to as tissue acidosis – and cortical spreading depolarization.
Typically, research groups submit figures from their publications for consideration as cover art in printed scientific journals. Being selected often underscores the significance of the research topic and the attention it has received within the scientific community. In this exceptional case, however, the editorial board of the Journal of Cerebral Blood Flow & Metabolism chose the Cerebral Blood Flow and Metabolism Research Group’s figures for the cover on both occasions on their own initiative, without any formal submission. This represents an extraordinary recognition, especially for a team of just six members.
“Many journals allow authors to submit their figures for consideration as cover art, but we never even thought about it. So, when we unexpectedly learned that the editor had chosen our figure for the October cover, we were thrilled. Then, after returning from the winter break in January, I checked my email and found another message waiting for me,” Dr. Eszter Farkas recalls. “The Journal of Cerebral Blood Flow & Metabolism typically features our work once a year. This time, however, we had two publications within six months, which is a great achievement for such a small team.”
The cover image of the newly released February issue of the journal illustrates the process of tissue acidification in the brain. According to Dr. Eszter Farkas, whose research group specializes in cortical spreading depolarization, this phenomenon plays a crucial role in post-stroke pathology:
“After a stroke, the brain rapidly loses its ability to buffer pH changes. Tissue oxygen deprivation causes a shift from aerobic to anaerobic metabolism along with the accumulation of lactic acid and protons. In this process, spreading depolarization events emerge as central elements to determining hypoxia-induced tissue acidosis. In our publication, we outlined how this acidic environment activates various cell death pathways. Although numerous independent studies have been conducted in this field, researchers are often unaware of each other’s work. So, our aim with this review was to connect parallel research areas that share underlying links, which are rarely recognized,” explains Dr. Eszter Farkas, professor and stroke research specialist at the University of Szeged.
Photo by Ádám Kovács-Jerney
The role of cortical spreading depolarization in worsening stroke outcomes was also the focus of the study highlighted on the cover of the Journal of Cerebral Blood Flow & Metabolism’s October issue.
While current stroke treatments aim to restore blood flow, Dr. Eszter Farkas notes that this process does not always unfold as expected:
"At present, the only available therapeutic interventions for stroke involve either dissolving the thrombus that blocks the cerebral artery, a process known as thrombolysis, or physically removing it through a procedure called thrombectomy. After the clot is removed, the vessel is expected to regain patency, and blood flow should be restored to the affected brain region in a process referred to as reperfusion. However, in more than half of cases, circulation does not fully recover despite successful clot removal. This phenomenon is known in the literature as reperfusion failure or no-reflow. What happens is that, although the primary obstruction is resolved, microcirculatory perfusion does not always resume as expected. The reasons for this are not yet fully understood, but several explanations have been proposed. One hypothesis suggests that inflammatory processes may be at play, leading to an accumulation of white blood cells that, in their activated state, adhere more easily to the vessel walls, become trapped, and block small blood vessels. Another theory posits that cerebral vessels remain constricted after thrombectomy for some reason, thereby impeding proper circulation. There is also a specific type of capillary cell, known as the pericyte, that has been implicated in this process. Some researchers believe that these contractile cells – with extensions wrapping around microvessels – may induce persistent vasoconstriction, thereby preventing full restoration of blood flow after thrombectomy.”
Expanding on this, Dr. Farkas details the research group’s findings:
“Our research suggests that it is cortical spreading depolarization that predisposes the cerebral vasculature to reperfusion failure. In experimental models, we induced stroke in rodents by occluding a cerebral artery for one hour, during which spreading depolarization occurred in some cases but not in others. Our observations revealed that, despite the resolution of the occlusion, subsequent reperfusion continued to be suboptimal or inadequate in the presence of depolarization. In contrast, in the absence of depolarization, blood flow was fully restored following the ischemic event. These findings indicate that cortical spreading depolarization may play a causative role in reperfusion failure.”
Original Hungarian text by Sándor Panek
Feature photo: Prof. Dr. Eszter Farkas, head of the Cerebral Blood Flow and Metabolism Research Group of the University of Szeged
Photo by Ádám Kovács-Jerney
