What is the mechanism behind the sensitivity of traumatic brain injury? Correlation between mitochondria and vascular dysfunction
Trying to cope with the complexity of brain health, we delve into the world of traumatic brain injury (TBI), a common but confusing health issue that affects millions each year. These injuries range from mild to severe, triggering a series of hidden but significant brain changes. When we consider the consequences, stories develop over time and often remain undiscovered at first glance, and stories become more complicated. Our exploration aims to illuminate these hidden consequences, revealing key changes that occur after injury.
Researchers led by Dr. Gerben Van Hameren and Professor Alon Friedman of Dalhousie University and their team conducted an in-depth investigation into the link between mitochondrial dysfunction and vascular disorders after TBI. Their pioneering research, published in the neurobiology of the disease, elucidates the cascade consequences of brain trauma events.
Dr. Gerben Van Hameran said: “Mitochondria are an important part of almost all human cells. Their most famous role is to provide energy so that the cells can play their best. In this process, mitochondria produce reactive oxygen species, which can be a damaging effect. but may also be useful, for example during immune processes or as messenger molecules. Mitochondria also plays a role in managing the amount of calcium in cells.”
TBI is a major health problem around the world, divided into two stages: direct primary damage and subsequent secondary damage that develops over time. Dr. Van Hameren explained: “Traumatic brain injury (TBI) is a major source of global health problems affecting 40 million people each year. TBI-related injuries are classified as primary or secondary . Primary injury occurs instantaneously and may involve brain bruises, blood clots in the skull, damage to the brain’s white matter, and damage to the brain’s cell structure. On the contrary, secondary occurs within minutes, hours or days after the impact Injury. The mechanism behind secondary damage is complex and not fully understood”.
Their study used a moderate TBI model involving a method to simulate head effects that showed immediate drop in blood oxygen levels and significant decline in nervous system health, as in the score of lower nervous system severity (NSS) show. Dr. Van Hameren elaborated: “We first evaluated functional, anatomical and behavioral results after simulated moderate effects. This moderate effect resulted in a mortality of 2.5%. In the surviving animals, we measured acute blood oxygen at impact The decline in levels. Behavioral analysis showed that the neurologic health score decreased 20 minutes after impact. The distribution of neurologic health scores was bimodal 48 hours after impact.”
A key finding of this study is that the frequent occurrence of cortical diffusion depolarization (CSD) after TBI is associated with a significant decline in nervous system health. “Consistent with previous studies, we recorded CSDs and associated spreading depression of brain activity in both hemispheres immediately following TBI,” Dr. van Hameren noted, “These CSDs were seen as a near shift in the voltage along with a suppression of the brain’s electric Signal. Records with two electrodes or changes in light signals through the skull confirm the propagation of events. “In Friedman’s lab, we investigated how traumatic brain injury leads to the blood-brain barrier. How damage and blood-brain barrier leakage are associated with brain diseases, especially epilepsy. In some of our studies (Aboghazleh et al., 2021; Parker et al., 2022), we noticed the importance of depolarization of cortical diffusion. Since only 50% of head injuries lead to depolarization spread, so this phenomenon may be the most important factor in long-term outcomes.
Further examination of mitochondrial behavior during CSD showed an increase in mitochondrial reactive oxygen species (ROS), especially near large blood vessels. “Despite the narrowing of blood vessels and reduced blood flow after CSD, low oxygen levels were not measured. We hypothesized that the oxygen use of mitochondria in these TBI animals was impaired.
Electron microscopy provides a more detailed view of vascular and mitochondrial changes after TBI. “After TBI, blood vessels in the brain appear to contract due to reduced roundness compared to the control group. We also observed signs of damage to the internal structure of mitochondria, mainly in the support cells and cells that control vascular tension, and Not in nerve or lining cells. TBI-induced cell type changes.
The study concluded that mitochondrial dysfunction significantly contributed to abnormal vascular responses observed in the case of increased metabolic demand, such as CSD and TBI seizures. Dr. Van Hameren stressed: “Mitochondrial dysfunction is the response of vascular abnormalities to increased metabolic demand, such as during CSD and seizures. Therefore, mitochondrial and vascular dysfunction during CSD may underlie TBI results. .”
This study represents an important milestone in understanding the complex internal operation of TBI, which provides a path to targeted strategies to reduce secondary damage and improve outcomes in affected individuals.
Journal Reference
Gerben van Hameren, Jamil Muradov, Anna Minarik, Refat Aboghazleh, Sophie Orr, Shayna Cort, Keiran Andrews, Caitlin McKenna, Nga Thy Pham, Mark A. MacLean, Alon Friedman. “Mitochondrial dysfunction is the basis for impaired neurovascular coupling after traumatic brain injury”, Disease Neurobiology, 2023, doi:
About the Author
Gerben Van Hameren He is a Dutch neuroscientist with expertise in mitochondrial function in the nervous system. After receiving his bachelor’s degree in biomedical science and a master’s degree in basic neuroscience at Maastricht University, he conducted his PhD dissertation at the Montpellier Neuroscience Institute in Montpellier, France. There, he measured mitochondrial ROS and ATP using adeno-associated virus and multiphoton microscopy in the sciatic nerve and brain nerves to study Charcot-Marie-Marie-tooth disease and demyelination.
Currently, he is a postdoctoral researcher at Dalhousie University in Halifax, Canada, where he studies mitochondrial and vascular dysfunction in rats following brain injury, seizures and depolarization of cortical diffusion. In this work, he was funded by Mitacs and received the Cure Epilepsy Award.
Alon Friedman He is a professor of neuroscience and serves as the chairman of epilepsy research at Dalhousie University in Halifax and is a professor in the Department of Brain and Cognitive Sciences at Negivben Gurion University in Israel. He completed his medical and doctoral training at Ben-Gurion University and received his neurosurgery training at the Soroka University Medical Center in Israel. He conducted postdoctoral training at the Charité Medical University in Berlin and served as a researcher for Alexander von Hambot.
His work has been recognized by several international awards, most notably the International Michael Epilepsy Research Award, the Mercator Professorship position at Charité Medical University in Berlin and the Foulkes Foundation Research Award.
His research focuses on exploring the interaction between vascular and neuronal systems within the central nervous system, especially microvascular pathology and blood-brain barrier dysfunction involved in the pathogenesis of injury-related epilepsy and neurodegeneration.
