Hemodynamic Depression and Microthrombosis Formation in the Peripheral Areas of Cerebral Contusion

脑挫裂伤周围区域的血流动力学抑制和微血栓形成

• 批准号: 07671547
• 负责人: YAMAMOTO Takamitsu
• 金额: $ 1.41万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671547/
• 关键词: trauma; brain injury; cerebral contusion; cerebral blood flow; microthrombosis; brain edema; tissue osmolality; rat; 血管内凝固; 血小板

Cerebral contusious sometimes cause progressive or delayd deterioration of neurological symptoms, which may result from secondary injury processes of the traumatized brain. It is important to elucidate pathophysiology underlying secondary brain damages, since one principal goal of treatments for traumatic brain injury is to prevent such secondary damages following the injury. In the present syudy, in order to elucidate the mechanisms of contusion-induced secondary cell injury processes, we investigated hemodynamic changes in cerebral contusion, and effects of anti-thrombosis and anti-coagulate drugs were tested in a rat cortical contusion induced by a controlled cortical impact device. Results (1)Histological examinations revealed that the initial histopathological finding in the peripheral area of contusion was microthrombosis formation, followed by brain edema and necrosis formation. These changes progressively extended to peripheral area surrounding the contusion. (2)In the central … More area of contusion, cerebral blood flow (CBF) was decreased to the ischemic level within 5-15 min after the injury induction. In the peripheral area, CBF was decreased to 20% of the beseline, returned to 40-60% level, and then decreased again to the ischemic level without any recovery. (3)A inhibitor of platelet activating factor (PAF), etizolam, attenuated the contusional necrosis formation as well as decreasing CBF in the peripheral but not in the central area of contusion. (4)The tissue osmolality of contusion increased immediately following the injury, and the tissue water content increased thereafter. (5)The concentration of the tissue cations (total amount of [Na^+]+[K^+] in the contusion did not show any significant changes, indicating inorganic ions do not mainly participate in the tissue osmolality increase. Discussion The results of the present study indicate that the microthrombosis formation in the peripheral areas of contusion may contribute to the secondary cell injury processes in cerebral contusion. Anti-thrombosis with a PAF antagonist has a therapeutic potential to attenuate the lschemic btain damage and subsequent edema formation following the contusion. The progressive increase in tissue osmolality is another cause of contusion-induced edema formation. Increases in metabolic intermediate osmoles and/or idiogenic osmoles resulting from the catabolic degradation of intracellular high molecular substances, e.g.phospholipids in cell membrane, may play a major role for the formation of osmotic potential and a resultant brain edema in the cerebral contusion. Less

脑挫伤有时会引起神经系统症状的进行性或迟发性恶化，这可能是由于创伤性脑的继发性损伤过程所致。阐明继发性脑损伤的病理生理学是很重要的，因为创伤性脑损伤治疗的一个主要目标是防止这种继发性脑损伤。为了阐明脑挫伤致继发性细胞损伤的机制，我们研究了脑挫伤后血流动力学的变化，并在受控制的皮质撞击装置诱导的大鼠皮质挫伤中测试了抗血栓和抗凝药物的作用。结果(1)组织病理学检查显示，挫伤外周区最初的组织病理学表现为微血栓形成，其次是脑水肿和坏死形成。这些变化逐渐扩展到挫伤周围的外周区域。(2)损伤诱导后5 ~ 15 min，中央区脑血流量（CBF）下降至缺血水平。外周区CBF下降至基线的20%，恢复到40-60%，然后再次下降到缺血水平，没有任何恢复。(3)血小板活化因子（PAF）抑制剂乙替唑仑可减轻挫伤坏死的形成，并降低挫伤外周区的CBF，但对挫伤中心区没有作用。(4)损伤后组织渗透压立即升高，组织含水量随之升高。(5)挫伤组织阳离子浓度（[Na^+]+[K^+]总量）未出现明显变化，说明无机离子不主要参与组织渗透压升高。本研究结果提示，脑挫裂伤外周区微血栓形成可能参与脑挫裂伤的继发性细胞损伤过程。抗血栓形成与PAF拮抗剂具有治疗潜力，以减轻缺血性脑损伤和随后的水肿形成后挫伤。组织渗透压的逐渐增加是挫伤性水肿形成的另一个原因。由于细胞内高分子物质（如细胞膜磷脂）的分解代谢降解，代谢中间渗透分子和/或特发性渗透分子增加，可能在脑挫裂伤中渗透电位的形成和脑水肿中起主要作用。少

项目成果

Yamamoto T,Katayama Y,Tsubokawa T,et al.: "Pharmacological classification of central post-stroke pain : comparison with the results of chronic motor cortex stimulation therapy" Pain. 72. 5-12 (1997)

Yamamoto T，Katayama Y，Tsubokawa T，等人：“中枢性中风后疼痛的药理学分类：与慢性运动皮层刺激疗法的结果比较”疼痛。

山本 隆充、片山 容一、他: "骨傷のない頚椎損傷急性期の治療法:Killed end corticospinal evoked potentialの推移からみた治療法の検討" 日本パラプレジア医学会雑誌. 9(1). 24-25 (1996)

Takamitsu Yamamoto、Yoichi Katayama等：“无骨损伤的颈椎损伤急性期的治疗方法：从杀伤端皮质脊髓诱发电位转变的角度检查治疗方法”日本截瘫医学会杂志。 9（1）。24-25（1996）

Mori T,Katayama Y,Yamamoto T,et al.: "Progressive edema formation in contused brain : Role of tissue osmolality and ion concentrations" Advances in Neurotrauma Research. 8. 15-18 (1996)

Mori T、Katayama Y、Yamamoto T 等人：“挫伤脑中的进行性水肿形成：组织渗透压和离子浓度的作用”神经创伤研究进展。

Katayama Y,Koshinaga M,Tsubokawa T,et al.: "Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury." Brain Pathology. 5. 427-435 (1995)

Katayama Y、Koshinaga M、Tsubokawa T 等人：“兴奋性氨基酸介导的离子通量在创伤性脑损伤中的作用。”

Kurihara J,Yamamoto T,Katayama Y,et al.: "Experimental spinal cord injury induced by a controlled impact device : Electrophysiological and histological investigations" Advances in Neurotrauma Research. 8. 61-64 (1996)

Kurihara J、Yamamoto T、Katayama Y 等人：“受控冲击装置引起的实验性脊髓损伤：电生理学和组织学研究”神经创伤研究进展。