Kyu-Sun Choi1, Han-Jun Kim2, Sun Hee Do2, Se Jin Hwang3, Hyeong-Joong Yi4. 1. Department of Neurosurgery, College of Medicine, Hanyang University, Seoul, Republic of Korea. 2. Department of Clinical Pathology, College of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea. 3. Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, Republic of Korea. 4. Department of Neurosurgery, College of Medicine, Hanyang University, Seoul, Republic of Korea. Electronic address: hjyi8499@hanyang.ac.kr.
Abstract
OBJECTIVE: Hydrogen inhalation has been found to be neuroprotective and anti-oxidative in several brain injury models. Building on these studies, we investigated potential neuroprotective effects of hydrogen inhalation in a rat model of intracerebral hemorrhage (ICH), focusing on apoptosis and inflammation. METHODS: Forty-five 8-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 15 per each group): a sham group, ICH group, and ICH + hydrogen group. Induction of ICH was performed via injection of 0.23 U of bacterial collagenase type IV into the left striatum. Hydrogen was administered via spontaneous inhalation. Mortality and neurologic deficits were investigated at 6, 24, and 48 h after ICH. To investigate the antioxidative activity of hydrogen gas, the expression of malondialdehyde was measured. Real-time polymerase chain reaction analyses of TNF-a, IL-1b, BDNF, and caspase-3 expression were used to detect anti-inflammatory and anti-apoptotic effects. Neuroprotective effect was evaluated by immunohistochemical and TUNEL staining. RESULT: At 6, 24 and 48 h post-intracerebral hemorrhage, animals showed brain edema and neurologic deficits, accompanied by up-regulation of TNF-a, IL-b, BDNF, and caspase-3, which is indicative of neuroinflammation, neuroprotection, and apoptosis. Hydrogen treatment significantly reduced the level of oxidative stress, neuroinflammation, neuronal damage, and apoptosis-related genes. This was accompanied by increased neurogenesis and expression of growth factor-related genes at <24 h, but not 48 h, after ICH. CONCLUSION: H2 gas administration exerted a neuroprotective effect against early brain injury after ICH through anti-inflammatory, neuroprotective, anti-apoptotic, and antioxidative activity.
OBJECTIVE:Hydrogen inhalation has been found to be neuroprotective and anti-oxidative in several brain injury models. Building on these studies, we investigated potential neuroprotective effects of hydrogen inhalation in a rat model of intracerebral hemorrhage (ICH), focusing on apoptosis and inflammation. METHODS: Forty-five 8-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 15 per each group): a sham group, ICH group, and ICH + hydrogen group. Induction of ICH was performed via injection of 0.23 U of bacterial collagenase type IV into the left striatum. Hydrogen was administered via spontaneous inhalation. Mortality and neurologic deficits were investigated at 6, 24, and 48 h after ICH. To investigate the antioxidative activity of hydrogen gas, the expression of malondialdehyde was measured. Real-time polymerase chain reaction analyses of TNF-a, IL-1b, BDNF, and caspase-3 expression were used to detect anti-inflammatory and anti-apoptotic effects. Neuroprotective effect was evaluated by immunohistochemical and TUNEL staining. RESULT: At 6, 24 and 48 h post-intracerebral hemorrhage, animals showed brain edema and neurologic deficits, accompanied by up-regulation of TNF-a, IL-b, BDNF, and caspase-3, which is indicative of neuroinflammation, neuroprotection, and apoptosis. Hydrogen treatment significantly reduced the level of oxidative stress, neuroinflammation, neuronal damage, and apoptosis-related genes. This was accompanied by increased neurogenesis and expression of growth factor-related genes at <24 h, but not 48 h, after ICH. CONCLUSION:H2 gas administration exerted a neuroprotective effect against early brain injury after ICH through anti-inflammatory, neuroprotective, anti-apoptotic, and antioxidative activity.