The Application of Hyperbaric Oxygen Therapy in Cerebral Resuscitation

　　Original, May 5, 2016, Wang Peidong, Kangfuhui

　　Hyperbaric medicine falls under the umbrella of hyperbaric physiology and primarily encompasses diving medicine and hyperbaric oxygen therapy.

　　HBO is a relatively young subspecialty of clinical medicine that is widely used in the treatment of diseases across internal medicine, surgery, obstetrics and gynecology, pediatrics, and other disciplines, demonstrating favorable therapeutic outcomes and promising prospects.

　　Since 1964, when Professor Li Wenren built China’s first medical hyperbaric oxygen chamber in Fuzhou, the country’s hyperbaric oxygen medicine has experienced rapid development over the past five decades. China now ranks first worldwide in the number of hyperbaric chambers, the number of patients receiving hyperbaric oxygen therapy, the variety of conditions treated with this modality, and the number of healthcare professionals—physicians, nurses, and technicians—engaged in hyperbaric oxygen care.

　　Hyperbaric Oxygen Therapy and Traumatic Brain Injury

　　Pathophysiology of Traumatic Brain Injury

　　Hemodynamic changes: divided into a hypoperfusion phase and a hyperemia phase.

　　Ischemic phase: Endothelial cell injury and swelling impede microcirculation; damaged endothelial cells activate platelets, leading to the formation of microthrombi that occlude the microvasculature; endothelial dysfunction reduces nitric oxide (NO) production, while the lesion site generates abundant vasoactive substances (such as histamine, neuropeptides, and thromboxane) and intracellular calcium overload, all of which precipitate microvascular spasm, thereby decreasing regional blood perfusion at the lesion.

　　Hyperemia phase: Following the hypoperfusion phase, cerebral tissue experiences excessive perfusion. This hyperemic phase typically occurs on the second or third day after injury. Although increased blood flow can enhance oxygen and nutrient delivery, it may also precipitate ischemia-reperfusion–induced brain injury, calcium overload, activation of neutrophils and platelets, elevated levels of excitatory amino acids, and excessive cellular apoptosis.

　　2. Capillary leak syndrome (CLS) is a severe complication of SIRS, characterized by endothelial damage to capillaries caused by various etiologies. Increased capillary permeability leads to the extravasation of large volumes of fluid, electrolytes, and colloids—primarily albumin—into the interstitial space, rapidly resulting in hypoproteinemia, hemoconcentration, hypovolemia, and even hypovolemic shock. Concurrently, interstitial edema develops in multiple organs; when leakage occurs in the lungs, brain, or abdominal cavity, the clinical course deteriorates precipitously. Meanwhile, secondary increases in aldosterone secretion give rise to sodium retention, water retention, and oliguria.

　　CLS is divided into three phases.

　　Phase I is the pre‑leakage phase, which primarily refers to the early stage of trauma or shock management—characterized by extensive blood and fluid transfusions aimed at stabilizing circulation. The hallmark clinical features during this phase are hypovolemia and severe hypotension; without rapid and substantial volume replacement, it is often difficult to sustain basic vital signs.

　　Stage II is the leakage phase, also known as the phase of forced extravascular fluid sequestration. The principal pathophysiological features of this stage include increased systemic capillary permeability, with large volumes of intravascular fluid shifting into the interstitial space, leading to a reduction in effective circulating blood volume and inadequate tissue perfusion. Clinically, this manifests as progressively worsening hypotension, rapidly developing generalized edema extending from the face, neck, and extremities to the trunk, often accompanied by pulmonary and cerebral edema. Pleural effusion, ascites, and pericardial effusion may also occur. In a minority of cases, the clinical picture is dominated by leakage in a single organ, such as cerebral edema, pulmonary edema, or abdominal cavity edema, among others.

　　Phase III is the recovery phase, also known as the vascular reperfusion phase. During this phase, capillary permeability gradually returns to normal, macromolecules are progressively reabsorbed, interstitial fluid is returned to the vasculature, and blood volume increases. If the fluid within the vessels is not promptly drained during this phase, acute left ventricular failure and acute pulmonary edema can easily develop.

　　3. Cerebral edema: Increased permeability of the blood–brain barrier leads to interstitial edema; calcium overload, an increase in free radicals, elevated nitric oxide levels, and an excess of excitatory amino acids can all contribute to cerebral edema.

　　Ischemia and hypoxia during the hypoperfusion phase following traumatic brain injury can lead to neuronal damage, while the hyperemic phase may precipitate secondary injury to brain tissue; both ultimately result in cerebral edema. Therefore, enhancing tissue oxygenation and controlling cerebral edema are critical components of the management of traumatic brain injury.

　　Hyperbaric Oxygen Therapy for Traumatic Brain Injury

　　Mechanism of hyperbaric oxygen (HBO) therapy

　　① Increases blood oxygen concentration, enhances interstitial oxygen diffusion, and ameliorates cerebral hypoxia. ② Promotes cerebral vasoconstriction, reduces cerebral blood flow, decreases vascular permeability, alleviates cerebral edema, and lowers intracranial pressure. ③ Inhibits platelet and erythrocyte aggregation, reduces blood viscosity, increases vertebral artery perfusion, improves the hypoxic state of the brainstem and the reticular activating system, and facilitates recovery of consciousness. ④ Reduces free radical production, regulates intracellular Ca²⁺ levels, enhances cell membrane stability, attenuates apoptosis, suppresses post‑traumatic inflammatory responses, and promotes neurological functional recovery. ⑤ Facilitates axonal regeneration and restoration of neural conduction function.
 

　　Research on the mechanisms of hyperbaric oxygen therapy

　　Huang Xiang and colleagues, using magnetic resonance imaging, conducted a longitudinal study to assess the effects of hyperbaric oxygen (HBO) therapy on cerebral tissue changes in rats with severe traumatic brain injury. They found that HBO treatment promotes histomorphological repair and exerts a beneficial effect in accelerating lesion clearance and the resolution of hematoma and edema. Yue Lina and her team suggested that HBO therapy may mitigate the inflammatory response following traumatic brain injury by suppressing the expression of pro-inflammatory mediators such as IL‑1β, TNF‑α, and ICAM‑1. Furthermore, Wen Jianfeng and colleagues reported that HBO increases the levels of insulin‑like growth factor‑1 (IGF‑1) and the active form of NF‑κB (P50) in brain tissue, thereby protecting and facilitating the repair of injured neurons.

　　HBO’s role in promoting the repair and regeneration of neural tissue following brain injury has also garnered increasing attention and has become a research hotspot in recent years.

　　Studies have shown that hyperbaric oxygen therapy (HBO) increases the expression of bone morphogenetic protein‑4 (BMP‑4) and BMP‑4 mRNA in the hippocampus following brain injury, as well as the expression of nestin protein and nestin mRNA. BMP‑4 can induce the differentiation of neural stem cells (NSCs) into neurons and also promote their differentiation into astrocytes, thereby contributing to neural repair after brain injury.

　　Directions for Disciplinary Development

　　Hyperbaric oxygen therapy promotes the repair and regeneration of tissue damage.

　　Tissue injury repair and regeneration are major research priorities in the medical community, both domestically and internationally. The aim of this study is to employ advanced techniques from molecular biology, biochemistry, and immunology to investigate the therapeutic effects of hyperbaric oxygen on brain and spinal cord injuries, skin flaps, and organ transplantation, as well as to elucidate the underlying mechanisms by which hyperbaric oxygen influences the repair and regeneration of injured tissues. This work seeks to clarify the clinical value and advantages of hyperbaric oxygen therapy and to provide theoretical and practical foundations for its application in clinical practice.

　　2. Hyperbaric oxygen therapy for ischemic and hypoxic diseases

　　3. Standardized treatment of carbon monoxide poisoning and other harmful gas poisonings with hyperbaric oxygen therapy