Cerebral contusion and endothelial damages following neutrophil adhesion

中性粒细胞粘附后的脑挫裂伤和内皮损伤

• 批准号: 11671397
• 负责人: YAMAMOTO Takamitsu
• 金额: $ 2.3万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671397/
• 关键词: cerebral contusion; leukocyte; endothelium; P-selectin; vinblastin; immunosuppressant; brain edema; rat; myeloperoxidase活性; 脳血流; 血栓形成; 免疫抑制薬

Cerebral contusion induces a tissue inflammatory response following neutrophil adhesion and migration into brain tissue, which may contribute to secondary cell injury processes in contusion and surrounding brain. In the present study, we investigated effects of immunosuppressants (Cyclosporin A, FK506) and anti-P-selectin antibody on contusion-induced edema formation and tissue damages, using a controlled cortical impact model of rat. The doze of 1 mg/kg FK506 significantly attenuated the contusion edema and subsequent brain damages (p<0.01). The dose of 10 mg/kg FK506, however, did not show such therapeutic effects. The cyclosporin A administration showed the tendency to reduce the brain damage, but the changes were not statistically significant. The administration of anti-P-selectin antibody immediately after the injury induction markedly attenuated the neutrophil accumulation, which was evaluated by histological studies and tissue myeloperoxidase activities, and the subsequent edema formation as well as necrosis formation (p<0.01). These findings suggest that activation of neutrophils contributes to contusion-induced secondary cell damages, and inhibition of such processes provides therapeutic effects for the treatments of cerebral contusion.

脑挫裂伤在中性粒细胞粘附和迁移到脑组织后诱导组织炎症反应，这可能导致挫伤和周围大脑的继发性细胞损伤过程。在本研究中，我们使用大鼠受控皮质冲击模型研究了免疫抑制剂（环孢素 A、FK506）和抗 P-选择素抗体对挫伤引起的水肿形成和组织损伤的影响。 1 mg/kg FK506 剂量可显着减轻挫伤水肿和随后的脑损伤（p<0.01）。然而，10mg/kg FK506的剂量并未显示出这样的治疗效果。环孢素A给药显示出减少脑损伤的趋势，但变化不具有统计学意义。通过组织学研究和组织髓过氧化物酶活性以及随后的水肿形成和坏死形成来评估，在损伤诱导后立即施用抗P-选择素抗体显着减弱了中性粒细胞的积累（p<0.01）。这些发现表明，中性粒细胞的激活有助于脑挫伤引起的继发性细胞损伤，而抑制此类过程可为脑挫伤的治疗提供治疗效果。

项目成果

Kawamata, T., Katayama, Y., Mori, T., Aoyama, N., and Tsubokawa, T.: "Mechanism of the mass effect of cerebral contusion: ICP monitoring and diffusion MRI study"Acta Neurochirurgica. 81 (Suppl). 281-283 (2002)

Kawamata, T.、Katayama, Y.、Mori, T.、Aoyama, N. 和 Tsubokawa, T.：“脑挫裂伤占位效应的机制：ICP 监测和扩散 MRI 研究”《神经外科学报》。

TSUBOKAWA, T., Mori, T., Aoyama, N., Kawamata, T., Katayama, Y.: "Neuroprotective effects of immunosuppressant FK506 in cerebral contusion"Neurotraumatology. 22. 95-98 (1999)

TSUBOKAWA, T.、Mori, T.、Aoyama, N.、Kawamata, T.、Katayama, Y.：“免疫抑制剂 FK506 对脑挫裂伤的神经保护作用”神经创伤学。

Yamamoto T, Katayama Y, Oshima H, Fukaya C, Kawamata T, Tsubokawa T: "Deep brain stimulation for a persistent vegetative state"Acta Neurochirurgica. 79. 79-82 (2001)

Yamamoto T、Katayama Y、Oshima H、Fukaya C、Kawamata T、Tsubokawa T：“持续植物人状态的深部脑刺激”神经外科学报。

Kawamata, T., Katayama, Y., Mori, T., Aoyama, N., Tsubokawa, T.: "Mechanisms of the mass effect of cerebral contusion : ICP monitoring and diffusion MRI study"Acta Neurochirrugica. 81. 281-283 (2002)

Kawamata, T.、Katayama, Y.、Mori, T.、Aoyama, N.、Tsubokawa, T.：“脑挫裂伤占位效应的机制：ICP 监测和扩散 MRI 研究”《神经药物学报》。

片山容一, 川又達朗: "挫傷性脳浮腫の発生機転"神経外傷(Neurotraumatology). 23. 6-9 (2000)

Yoichi Katayama、Tatsuro Kawamata：“挫伤性脑水肿的发生机制”《神经创伤学》23. 6-9 (2000)。