Neuroprotective effects of mild hypothermia on brain injuries basic and clinical research on learning and functional disturbances

亚低温对脑损伤的神经保护作用、学习和功能障碍的基础和临床研究

• 批准号: 12470291
• 负责人: NAGAO Seigo
• 金额: $ 4.48万
• 依托单位: Kagawa Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470291/
• 关键词: Brain hypothermia; Cerebral ischmeia; Acute subdural hematoma; Intracerebral hemorrhage; Blood-brain barrier; Polymorphonuclear leukocytes; Brain edema; Rats; 脳低温療法; 脳浮腫; Matrix Metalloroteinase; 低体温療法; 機能障害; 重症脳損傷; 脳虚血(局所); 脳出血; 多核白血球; イ

We have investigated the neuroprotective effects of mild brain hypothermia on various injury models in rodents. In a model focal cerebral ischemia in rats, intraischemic and postischemic hypothermia significantly reduced the volume of infarction at 24 hours after ischemia. This protection was accompanied with significant reduction of polymorphonuclear (PMN) leukocytes infiltration into the injured-brain. In a model of acute subdural hematoma in rats, mild hypothermia with intravenous administration of alkalizing agent significantly protected the blood-brain barrier (BBB) from breakdown and reduced the brain edema formation. This treatment also reduced the size of infarction under the hematoma 7 days after the hematoma induction. In a model of intracerebral hematoma, mild hypothermia significantly protected the BBB from the breakdown and reduced the brain edema formation 24 hours after the induction of hematoma or thrombin. Mild hypothermia significantly reduced the infiltration of PMN leukocytes into the brain. Ina model of transient forebrain ischemia in gerbils, mild hypothermia almost completely protected the neurons in hippocampus from the neuronal death 7 days after the ischmeia but not completely protected the neurons 1 month after the ischemia. Combined treatment with mild hypothermia and NMDA receptor antagonist protected these neurons from the delayed death. In this project, we confirmed the protective effects of mild brain hypothermia on several brain injury models in rodents. These results will help the clarification the neuroprotective mechanisms of brain hypothermia and enhance the application of brain hypothermia in clinical settings

我们研究了亚低温对啮齿动物不同损伤模型的神经保护作用。在大鼠局灶性脑缺血模型中，缺血内和缺血后低温显著减少了缺血后24小时的脑梗塞体积。在这种保护作用的同时，中性粒细胞(PMN)在损伤脑组织中的渗透也显著减少。在大鼠急性硬膜下血肿模型中，亚低温联合静脉注射碱化剂可显著保护血脑屏障(BBB)免受破坏，减少脑水肿的形成。血肿诱导后7天血肿下梗塞范围缩小。在脑内血肿模型中，亚低温显著保护血肿或凝血酶诱导的24小时后血脑屏障的破裂，并减少脑水肿的形成。亚低温可明显减少中性粒细胞向脑内的渗透。在沙土鼠短暂性前脑缺血模型中，亚低温几乎完全保护了缺血7d后海马神经元的死亡，但不能完全保护缺血1个月后的神经元。亚低温和NMDA受体拮抗剂联合治疗对神经元延迟性死亡有保护作用。在本项目中，我们证实了亚低温对几种啮齿类动物脑损伤模型的保护作用。这些结果将有助于阐明脑低温的神经保护机制，促进脑低温在临床上的应用

项目成果

Masanobu Okauchi, Nobuyuki Kawai, Takehiro Nakamura, Masahiko Kawanishi, Seigo Nagao: "Effects of Mild Hypothermia and Alkalizing Agents on Brain Injuries in Rats with Acute Subdural Hematomas"Journal of Neurotrauma. 19(6). 741-751 (2002)

Masanobu Okauchi、Nobuyuki Kawai、Takehiro Nakamura、Masahiko Kawanishi、Seigo Nagao：“轻度低温和碱化剂对急性硬膜下血肿大鼠脑损伤的影响”神经创伤杂志。

岩瀬哲也: "大学附属病院所在地M町における地域医療需給状況の変遷(老人保健法施行直後、公的介護保険施行直後の15年) その1 K県国保レセプトにみる3大疾病(悪性新生物、脳血管疾患、虚血性心疾患)の外来医療"病院管理学会雑誌. 37・Suppl. 153 (2000)

岩濑哲也：“大学附属医院所在的M镇当地医疗供求状况的变化（高龄者保健法施行后15年、公共长期护理保险施行后立即） ） 第1部 三大疾病（恶性肿瘤、恶性肿瘤、“脑血管疾病、缺血性心脏病的门诊医疗”）医院管理学会杂志第37号・增刊第153号（2000年）

Nobuyuki Kawai, Takehiro Nakamura, Masanobu Okauchi, Seigo Nagao: "Effect of Hypothermia on Intracranial Hemodynamics and Ischemic Brain Damage-Studies in the Rat Acute Subdural Hematoma Model"Acta Neurochir. 76. 529-533 (2000)

Nobuyuki Kawai、Takehiro Nakamura、Masanobu Okauchi、Seigo Nagao：“低温对颅内血流动力学和缺血性脑损伤的影响——大鼠急性硬膜下血肿模型的研究”Acta Neurochir。

N.Kawai, T.Nakamura, S.Nagao: "Effects of Brain Hypothermia on Brain Edema Formation after Intracerebral Hemorrhage in Rats"Acta Neurochir (Suppl). 81. 233-235 (2002)

N.Kawai、T.Nakamura、S.Nagao：“脑低温对大鼠脑出血后脑水肿形成的影响”Acta Neurochir（增刊）。

河井信行, 中村丈洋, 長尾省吾: "脳虚血に対する低体温療法"脳神経外科. 30. 1273-1283 (2002)

Nobuyuki Kawai、Takehiro Nakamura、Shogo Nagao：“脑缺血的低温疗法”神经外科。 30. 1273-1283 (2002)