Extracellular vesicles combined with hyperbaric oxygen therapy as new strategies for the treatment of traumatic brain injury: A narrative review

Current primary therapies for traumatic brain injury focus on pharmacological treatment and supportive care, but newer therapies such as extracellular vesicles therapy and hyperbaric oxygen therapy are being vigorously investigated. This review explains the pathogenesis of traumatic brain injury and its sequelae, summarizes current treatment strategies, and highlights the therapeutic prospects of hyperbaric oxygen therapy and extracellular vesicle-based treatments. The current treatment strategies for traumatic brain injury mainly include surgical treatment, pharmacotherapy, and hyperbaric oxygen therapy. Surgical intervention is mainly utilized in the evacuation of intracranial hematomas and the relief of intracranial pressure. Pharmacological treatment includes neuroprotective agents, anti-inflammatory drugs, etc. Hyperbaric oxygen therapy can relieve cerebral hypoxia and promote neurological recovery. Extracellular vesicle therapy and hyperbaric oxygen therapy are two novel therapeutic modalities with great therapeutic potential. Extracellular vesicles are nano-sized extracellular vesicles secreted by cells, with the capacity to promote neural regeneration, suppress inflammatory responses, augment angiogenesis, and halt cellular apoptosis. hyperbaric oxygen therapy exerts therapeutic action via increased cerebral oxygenation, alleviation of brain tissue hypoxia, restoration of neurological function, and mitigation of neuroinflammation and cerebral edema. The simultaneous use of extracellular vesicle therapy and hyperbaric oxygen therapy can potentially produce synergistic effects, which may improve treatment outcomes and enhance patient prognosis. Extracellular vesicles are characterized by pleiotropic and multi-target regulatory capabilities, with notable advantages including superior biocompatibility, high stability, and controllable pharmacokinetics, all of which contribute to a significant improvement in safety for therapeutic applications. However, to date, the U.S. Food and Drug Administration (FDA) has not granted approval for any extracellular vesicle-based products for clinical use, primarily due to concerns related to safety, purity, and batch-to-batch consistency, resulting in a considerable gap in the understanding of their clinical safety profile. In contrast, hyperbaric oxygen therapy has been widely implemented in clinical practice. By augmenting oxygen delivery in the hypoxic cerebral environment, hyperbaric oxygen therapy shows therapeutic potential in traumatic brain injury, encompassing the attenuation of neuroinflammation, inhibition of apoptosis, reduction of intracranial pressure, and alleviation of cerebral edema. Nevertheless, the clinical application of hyperbaric oxygen therapy necessitates rigorous safety evaluations, particularly in special populations or patients with specific contraindications, such as those with untreated pneumothorax, active epilepsy, or delayed encephalopathy during the acute phase post-carbon monoxide poisoning. To guarantee treatment safety, strict control over oxygen concentration and compression rate is imperative to preclude potential adverse reactions. Currently, research on the combined therapy remains relatively limited, with applications restricted to certain animal experiments, and no definitive conclusions have been drawn regarding its safety characteristics. Further research is needed to explore the optimal combination therapy regimen, thereby developing more effective treatments for patients with traumatic brain injury.