Traumatic Brain Injury- Novel Strategies Targeting the Secondary Injury

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially among children and young adults. TBI presents a substantial burden to the patients, their families, and society and has become a critical public health problem with enormous economic consequences. Despite extensive basic and clinical research on TBI during the last three decades, few clinical trials have effectively improved TBI-related outcomes and no effective pharmacological interventions are yet available to date. TBI involves a primary injury from mechanical impact and secondary injury which occurs in hours and days following the primary injury and plays a large role in the brain damage and death that results from TBI. The secondary injury involves pathological changes of the tissues and cells of the brain, including the inflammatory response, apoptosis, disruption of the blood-brain barrier, formation of edema, oxidative stress, and excitotoxic damage. Since the secondary injury occurs over time, it provides opportunities for therapeutic interventions to limit or prevent further damage to the brain. Therefore, novel therapeutic strategies and pharmacotherapies that can effectively improve the neurological function after TBI need to be further explored.

Although the molecular mechanism that underlies secondary brain injury is not completely understood, dysfunctional cellular inter-organelle communication has emerged as a critical event in alterations following the primary insult. For example, studies show that the mitochondria play essential physiological roles in cells through mediating multiple signal transduction pathways, and mitochondrial function has been considered to play an important part in cell damage repair. More and more evidence shows that mitochondrial damage caused by TBI further induces early cell apoptosis, and astrocyte-derived mitochondria can alleviate impairments of neurons in the early phase of TBI. The maintenance or recovery of mitochondrial function thus can be considered as a potential protective strategy in TBI. Therefore, research to further reveal the underlying cellular and molecular mechanisms of secondary brain injury is essential to develop neuroprotective measures and provide treatments in clinical practices.

Neurocritical care is a key element for moderate or severe TBI management, aiming to optimize cerebral perfusion, oxygenation, and avoiding secondary injury. Neurocritical care bioinformatics is a new and increasingly important field in the treatment for TBI. It focuses on the acquisition and analysis of physiological and relevant data of patients with TBI, which relates to the prevention, detection, and management of the secondary brain injury. Currently, the multimodal neuromonitoring tools are used not only to detect intracranial pressure, cerebral perfusion pressure, but also to measure the brain tissue oxygen tension, cerebral oxygen utilization, and aerobic metabolism. Besides, advanced informatics tools are now being applied to analyze the large volume of clinical data routinely monitored in neurocritical care with the goal of identifying secondary brain injury and providing neurosurgeons with improved ability to target specific goals in the TBI management of TBI.

In this Research Topic, we welcome articles addressing both the molecular and cellular mechanisms of the secondary injury of TBI as well as the novel strategies related to TBI neurocritical care. The sub-themes include but are not limited to the following:
• Cellular and molecular mechanisms of the secondary brain injury following TBI
• Therapeutic strategies, such as mitochondrial protection and neuralrepair in TBI, which can be applied to improve the translation of preclinical models into successful clinical trials
• Multimodal monitoring for secondary brain injury and novel approaches for understanding and applying these data to neurocritical care