Hyperbaric oxygen therapy alleviates intestinal and brain damage in experimental necrotizing enterocolitis

Marsico, Ana Laura1; da Silva-Tomaeli, Stephanya C.2; Marques, Pamella S. B.3; Feres, Omar4; Lopes, Luiza S.3; Sbragia, Lourenco1,*

Author Information

1Division of Pediatric Surgery, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

2Division of Anatomy, Department of Morphology and Pathology, Federal University of Sao Carlos, Sao Carlos, SP, Brazil

3Division of Neuroanatomy, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

4Division of Coloproctology, Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, SP, Brazil

*Correspondence to: Lourenço Sbragia, PhD, sbragia@fmrp.usp.br.

Abstract

Necrotizing enterocolitis is the most common gastrointestinal emergency in newborns. Its etiology involves bacterial colonization, enteral formula feeding, and hypoxic-ischemic injury. The pathology of necrotizing enterocolitis is characterized by coagulation necrosis and bacterial overgrowth, with limited preventative methods available. In addition to affecting the intestine, this disease has long-term neurological consequences for survivors. Hyperbaric oxygen therapy, a well-established treatment for soft tissue infections and injuries caused by hypoperfusion, may serve as an alternative approach for necrotizing enterocolitis. In this study, a necrotizing enterocolitis model was developed in newborn Sprague–Dawley rat pups through the administration of a hyperosmolar formula, combined with exposure to hypothermia and hypoxia. The rat pups received hyperbaric oxygen therapy sessions at 3 absolute atmospheres for 2 hours each, which were administered over 1 or 2 days. The results demonstrated that hyperbaric oxygen therapy significantly reduced mortality in rats with necrotizing enterocolitis and preserved the number of brain cells in the hippocampus. Additionally, hyperbaric oxygen therapy increased the expression of nitric oxide synthase, intestinal fatty acid-binding protein, and superoxide dismutase 3 in the intestine, and elevated superoxide dismutase 3 levels in the hippocampus. These findings suggest that hyperbaric oxygen therapy not only reduces mortality but also mitigates the severity of intestinal and brain lesions in experimental necrotizing enterocolitis, preserving intestinal cell integrity and enhancing antioxidant mechanisms.

摘要

坏死性小肠结肠炎是新生儿最常见的胃肠道急症。其病因涉及细菌定植、配方奶喂养和缺氧缺血性损伤。坏死性小肠结肠炎的病理特征为凝固性坏死和细菌过度生长，目前可用的预防方法有限。该疾病除影响肠道外，还对存活者的神经系统造成远期影响。高压氧治疗是一种成熟的用于软组织感染和低灌注所致损伤的治疗方法，可能为坏死性小肠结肠炎提供一种新的干预策略。本研究通过给予新生Sprague-Dawley大鼠仔鼠高渗配方喂养，并结合低温和缺氧暴露，建立了坏死性小肠结肠炎模型。模型大鼠接受3个绝对大气压、每次2小时的高压氧治疗，治疗持续1天或2天。结果表明，高压氧治疗显著降低了坏死性小肠结肠炎大鼠的死亡率，并保护了海马区的脑细胞数量。此外，高压氧治疗还增加了肠道中一氧化氮合酶、肠道型脂肪酸结合蛋白和超氧化物歧化酶3的表达，并提高了海马区超氧化物歧化酶3的水平。这些研究结果表明，在实验性坏死性小肠结肠炎中，高压氧治疗不仅能降低死亡率，还能减轻肠道和脑部病变的严重程度，保护肠道细胞完整性并增强抗氧化机制。