Hyperbaric oxygen treatment in the experimental spinal cord injury model

Hyperbaric oxygen treatment in the experimental spinal cord injury model

Onur Yaman MD , Banu Yaman MD et al - The Spine Journal Volume 14, Issue 9, 1 September 2014, Pages 2184-2194
Oct 18, 2025
Hyperbaric oxygen treatment in the experimental spinal cord injury model

The Spine Journal

Volume 14, Issue 9, 1 September 2014, Pages 2184-2194

The Spine Journal

Basic ScienceHyperbaric oxygen treatment in the experimental spinal cord injury model

Author links open overlay panelOnur Yaman MD a, Banu Yaman MD b, Figen Aydın MD c, Ahmet Var MD d, Cüneyt Temiz MD e

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Abstract

Background context

Spinal cord trauma is a major cause of mortality and morbidity. Although no known treatment for spinal cord injury exists, a limited number of effective treatment modalities and procedures are available that improve secondary injury. Hyperbaric oxygen (HBO) treatment has been used to assist in neurologic recovery after cranial injury or ischemic stroke.

Purpose

To report the findings on the effectiveness of HBO treatment on rats with experimental traumatic spinal cord injury. Improvement was evaluated through motor strength assessment and nitrite level assay testing.

Study design

We randomly distributed 40 rats among 5 groups of 8 rats each: sham incurable trauma, induced trauma, HBO treatment begun at the 1st hour, HBO treatment begun at the 6th hour, and HBO treatment begun at the 24th hour.

Method

The HBO treatment was administered to rats in three of the groups and conducted in two 90-minute sessions, under an absolute atmospheric pressure of 2.4 at 100% oxygen for 5 days. In the motor strength evaluations, all the rats were observed during the inclined plane test and clinical motor examination on the first, third, and fifth days. In addition, the nitrite levels of spinal cord tissues on the sixth day were also studied.

Results

Results from the inclined plane levels and motor strength test from all the three groups undergoing HBO treatment were higher than those from Group 2. It was also determined that early HBO treatment resulted in higher recovery rates (groups 3 and 4). The highest levels were seen in the group in which the HBO treatments were started in the first hour (Group 3). It was noted that nitrite levels of rats in the group exposed to trauma increased, compared with the sham group, but increased levels also diminished after HBO treatments. Again, the greatest decrease in nitrite levels was evident in the group where the HBO treatment was started the earliest (Group 3).

Conclusions

Prompt HBO treatment after trauma significantly contributed to the clinical, histopathologic, and biochemical recovery of the rats.

Introduction

The spinal cord is unable to regenerate itself. Permanent damage occurs in patients who have experienced spinal cord injuries (SCIs) [1], [2]. There are two mechanisms that increase the risk of further damage in SCIs [3], [4], [5], [6]: primary mechanical injury and secondary ischemic injury. Mechanical harm occurs at the time of the event. These injuries cause damage to the nerves, the spinal cord itself, and/or spinal vascular structures [7]. Secondary injury is the harm sustained by metabolic and biochemical factors occurring within hours after the primary injury [8], [9]. Ischemia is one of the most significant factors leading to secondary injury with the chief problem in the early periods being inadequate perfusion [5], [10]. Energy failure after the ischemia leads to a decrease in adenosine triphosphate levels, followed by the commencement of anaerobic respiration. Fehlings and Tator [1] state that ischemia after trauma constitutes the basis of secondary injury, but ischemia is a treatable and revocable process. The primary purpose of all experimental and clinical studies on traumatic spinal cord injury is to reduce secondary injury.

Although the total number of pathologic mechanisms caused by SCIs is not precisely known, processes, such as nitric oxide (NO) accumulation, resulting from increases in both calcium and free radicals are mentioned [7], [11], [12], [13], [14], [15], [16]. Lipid peroxidation is considered to be the principal cause among them [17]. These oxidative processes begin as a result of increases in hydrogen peroxide, superoxide ions, and NO, which cause oxidative damage to lipids, nucleic acids, and proteins, with the destructive potential of these free radicals increasing further as they raise endogenous antioxidants in the body [18]. Of these free radicals, NO is a primary molecule that plays a key role in many physiological processes such as vascular tonus regulation, thrombocyte functions, neuronal communication, and body defense [19]. Nitric oxide and its metabolites are reported to increase, especially in inflammatory and infectious conditions. It is understood that excessive NO production in cerebral ischemia and epilepsy leads to neurotoxicity [20]. Nitric oxide is primarily an unstable gas, which rapidly turns to nitrite, nitrate, and peroxynitrite compounds [20], [21]. Because its half-life of metabolization is so short, tissue levels are difficult to determine. Levels of stable nitrite and nitrate end products may indirectly affect decisions regarding NO tissue levels. This method was used, for years, to determine NO tissue levels especially in experimental ischemia and reperfusion studies [20].

Hyperbaric oxygen (HBO) is one possible treatment and support approach after, or before, secondary injury and is administered in a closed pressure chamber, under pressure higher than one atmosphere allowing the patient to breathe pure oxygen through an oxygen mask, respiration cap, oxygen tent, or endotracheal tube. This is used to contribute to neurologic recovery after brain injury and cerebral ischemia [20], [22], [23], [24], [25]. The first experimental study in which HBO treatment was administered to spinal traumas was reported by Maeda [26]. Hyperbaric oxygen use for therapeutic purposes was seen for the first time in the study by Hartzog et al. [27].

Within the scope of our study, trauma and sham groups were set up to determine the rats' motor strength and nitrite levels in tissues after experimental rat spinal cord trauma. To reduce spinal cord ischemia, HBO treatment was administered at the 1st, 6th, and 24th hour after trauma. Differences among the groups were compared by the measurements taken from nitrite levels, motor strength evaluations, and histopathologic examinations of tissues, based on a tissue destruction scale.

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Section snippets

Materials and methods

Surgical operations within the scope of the study were performed in research laboratories on experimental animals at the Aegean University Hospital and Celal Bayar University Hospital, with permission given by the University of Dokuz Eylul Ethics Committee of Experimental Animals, reference number 23/2009. In total, 40 Sprague-Dawley rats (8 rats in each of the 5 groups) were used for the study. In each group, the rats weighed between 200 and 250 g and were grouped randomly to form five groups (

Results

After surgery, it was observed that 32 rats, in which spinal cord trauma had been caused, became paraplegic. Further observation noted that the motor strength of eight rats in the sham group, which went through laminectomy only, was healthy.

Discussion

The incidence of documented SCIs is from $7,500 to $10,000 annually. In developed countries, 32,000 new cases occur every year, which means an SCI occurs every 16 minutes. According to studies, injuries occur most frequently between the ages of 16 and 30 years [1], [2]. The survivors of SCIs cannot maintain normal lives. As a result of treatment expenses and individual labor loss, SCI costs the society from $1 to 5 million dollars per year. Prevention of labor loss depends on the effectiveness

Conclusions

Hyperbaric oxygen treatment has been shown to reduce ischemia, one of the most important causes of secondary damage. From this study, one can conclude that serial HBO treatment, after trauma, is useful and has clinical, histopathologic, and biochemical benefits.

Acknowledgments

The authors thank Wanda Reese (of Jade Medical Communications Group, Los Angeles, CA, USA) who provided professional English-language editing of this article before its final acceptance for publication.

References (45)

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Cited by (14)

Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy

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Therefore, the HBO-induced upregulation of neuronal autophagy levels may represent one of the mechanisms underlying the therapeutic effect of HBO on SCI. HBO therapy also may exert its effects by enhancing the partial pressure of oxygen in damaged spinal cord tissues, increasing blood oxygen diffusion distance, promoting the activity of antioxidant enzymes in spinal cord tissues, inhibiting free radical-mediated lipid peroxidation, and enhancing the antioxidant capacities of cell membrane lipid structures [14,21–23]. Currently, studies that focus on the effect of HBO on SCI-induced autophagy are rather rare.

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Written by Onur Yaman MD , Banu Yaman MD et al - The Spine Journal Volume 14, Issue 9, 1 September 2014, Pages 2184-2194