Hydrogen does not exert neuroprotective effects or improve functional outcomes in rats after intracerebral hemorrhage

Abstract

ABSTRACT(ROS) damage the blood-brain barrier and increase brain edema (8,22,30). Hydroxyl radicals and peroxynitrites are very strong ROS that react indiscriminately with nucleic acids, lipids, and proteins, resulting in DNA fragmentation, lipid peroxidation, and protein inactivation (4,5,10,20,21,24,26,27). edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of hydroxyl radicals and is used for the treatment of ischemic stroke in Japan. edaravone attenuates the edema and ischemic damage after ICH by reducing oxidative damage in a rat model of ICH (23), and so has increasingly been investigated for use in ICH. However, a review of 10 randomized controlled studies failed to find any beneficial effect of edaravone for the treatment of ICH (31). Therefore, more potent free radical scavengers may be needed.█ INTRODUCTION H ypertensive intracerebral hemorrhage (ICH) accounts for 10-20% of strokes (2). ICH can be devastating with high mortality rates ranging from 30% to 50% at 30 days, and many survivors remain severely disabled (1,3,7,28). The International Surgical Trial in Intracerebral Haemorrhage (STICH) study, a landmark trial of over 1,000 ICH patients, showed that emergent surgical hematoma evacuation via craniotomy within 72 hours of onset failed to improve outcome compared to a policy of initial medical management (19). In addition, no specific medical therapy is available, so the optimal management of ICH has not been definitively established. Increasing evidence suggests that reactive oxygen speciesAIm: Increasing evidence suggests that reactive oxygen species damage the blood-brain barrier and increase brain edema after intracerebral hemorrhage (ICH). Recently, strong clinical and experimental evidence has shown that hydrogen has potent protective cellular effects in various diseases. However, the effect of hydrogen on ICH remains unclear. The present study investigates whether hydrogen has neuroprotective effects and improves functional outcome in the rat ICH model. mATERIAl and mEThODS: ICH model was generated by injecting 50 μl autologous tail artery blood stereotactically into the right caudate nucleus of Sprague-Dawley rats. Rats were randomly divided into four groups: sham, ICH/vehicle, ICH/hydrogen gas, and ICH/hydrogen-rich saline groups. Hydrogen treatment was performed for 3 days. The evaluation of functional outcome was done before, and at 24 and 72 hours after ICH. Hemorrhage volume, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG), and brain water content were evaluated at 72 hours after ICH. RESUlTS:Hydrogen administration reduced the expression of 8-OHdG in the brain, but did not attenuate brain water content or improve functional outcome, regardless of administration route. CONClUSION:Hydrogen administration without surgery has no neuroprotective effect in the blood injection rat ICH model.

Molecular hydrogen: a preventive and therapeutic medical gas for various diseases

“…These opposing findings might be due to differing experimental conditions, such as different degrees of HI insult, age of pups, H 2 concentration, and length of H 2 exposure. A recent study showed that H 2 administration without surgery did not exert neuroprotective effects or improve functional outcomes in rats after intracerebral hemorrhage [ 109 ]. For spinal cord injury, H 2 treatment improved locomotor behavior recovery in rats [ 110 ] and neurological recovery in mice with experimentally-induced autoimmune encephalomyelitis [ 111 ].…”

Hydrogen inhalation promotes recovery of a patient in persistent vegetative state from intracerebral hemorrhage: A case report and literature review

“…Considering that the pathophysiological mechanisms of neural injury and recovery of consciousness in brain diseases are complicated, the effectiveness of H 2 gas treatment might be dependent on the severity of brain damage and the multiple underlying mechanisms of molecular H 2 . Therefore, it may or may not be effective for all inflammation and oxidation-based diseases[ 38 ].…”

Recent advances in the neuroprotective effects of medical gases

“…On the other hand, treatment with H 2 failed to relieve brain edema or exert a neuroprotective function, although it did decrease the expression of 8-hydroxy-2′-deoxyguanosine, in a rat model of intracerebral hemorrhage. This result may be attributed to the low H 2 concentration that was used in this study, or to the existence of a more complicated mechanism involving reactive oxygen species in intracerebral hemorrhage 76. Therefore, the protective effects of H 2 may differ according to the dosage and/or animal model that are used.…”