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Therapeutic Hypothermia Combined with Hydrogen Sulfide Treatment Attenuated Early Blood–Brain Barrier Disruption and Brain Edema Induced by Cardiac Arrest and Resuscitation in Rat Model
Neurochemical Research ( IF 3.7 ) Pub Date : 2022-11-24 , DOI: 10.1007/s11064-022-03824-5
Shenquan Cai 1 , Qian Li 2 , Jingjing Fan 1 , Hao Zhong 1 , Liangbin Cao 1 , Manlin Duan 1
Affiliation  

Brain injury remains a major problem in patients suffering cardiac arrest (CA). Disruption of the blood–brain barrier (BBB) is an important factor leading to brain injury. Therapeutic hypothermia is widely accepted to limit neurological impairment. However, the efficacy is incomplete. Hydrogen sulfide (H2S), a signaling gas molecule, has protective effects after cerebral ischemia reperfusion injury. This study showed that combination of hypothermia and H2S after resuscitation was more beneficial for attenuated BBB disruption and brain edema than that of hypothermia or H2S treatment alone. CA was induced by ventricular fibrillation for 4 min. Hypothermia was performed by applying alcohol and ice bags to the body surface under anesthesia. We used sodium hydrosulphide (NaHS) as the H2S donor. We found that global brain ischemia induced by CA and cardiopulmonary resuscitation (CPR) resulted in brain edema and BBB disruption; Hypothermia or H2S treatment diminished brain edema, decreased the permeability and preserved the structure of BBB during the early period of CA and resuscitation, and more importantly, improved the neurologic function, increased the 7-day survival rate after resuscitation; the combination of hypothermia and H2S treatment was more beneficial than that of hypothermia or H2S treatment alone. The beneficial effects were associated with the inhibition of matrix metalloproteinase-9 expression, attenuated the degradation of the tight junction protein occludin, and subsequently protected the structure of BBB. These findings suggest that combined use of therapeutic hypothermia and hydrogen sulfide treatment during resuscitation of CA patients could be a potential strategy to improve clinical outcomes and survival rate.



中文翻译:

治疗性低温联合硫化氢治疗可减轻大鼠模型中心脏骤停和复苏引起的早期血脑屏障破坏和脑水肿

脑损伤仍然是心脏骤停 (CA) 患者的主要问题。血脑屏障 (BBB) 的破坏是导致脑损伤的重要因素。治疗性低温被广泛接受以限制神经损伤。然而,功效是不完全的。信号气体分子硫化氢(H 2 S)对脑缺血再灌注损伤后具有保护作用。这项研究表明,复苏后低温和 H 2 S 的组合比低温或 H 2更有益于减轻 BBB 破坏和脑水肿单独治疗。CA 由心室颤动诱导 4 分钟。通过在麻醉下将酒精和冰袋施加到体表来进行低温治疗。我们使用硫氢化钠 (NaHS) 作为 H 2 S 供体。我们发现 CA 和心肺复苏 (CPR) 引起的全脑缺血导致脑水肿和 BBB 破坏;低温或H 2 S治疗在CA和复苏早期减轻脑水肿,降低通透性,保留BBB结构,更重要的是改善神经功能,提高复苏后7天生存率;低温和 H 2 S 治疗的组合比低温或 H 2治疗更有益单独治疗。有益作用与基质金属蛋白酶 9 表达的抑制有关,减弱了紧密连接蛋白 occludin 的降解,随后保护了 BBB 的结构。这些发现表明,在 CA 患者的复苏过程中联合使用治疗性低温和硫化氢治疗可能是改善临床结果和生存率的潜在策略。

更新日期:2022-11-27
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