Protective effect of C1 esterase inhibitor on reperfusion injury in the rat middle cerebral artery occlusion model

• Published in: Neurosurgery Vol. 52; no. 2; pp. 395 - 401
• Main Authors: Akita, Nobuhisa, Nakase, Hiroyuki, Kaido, Takanobu, Kanemoto, Yukihide, Sakaki, Toshisuke
• Format: Journal Article
• Language: English
• Published: United States 01-02-2003
• Subjects: Animals; Brain - blood supply; Brain - pathology; Complement C1 Inactivator Proteins - pharmacology; Infarction, Middle Cerebral Artery - pathology; Leukocyte Count; Male; Neurons - drug effects; Neurons - pathology; Peroxidase - metabolism; Rats; Rats, Wistar; Regional Blood Flow - drug effects; Reperfusion Injury - pathology
• ISSN: 0148-396X
• DOI: 10.1227/01.NEU.0000043710.61233.B4

The complement system is thought to play a major role in initiating some of the inflammatory events that occur during reperfusion injury. The aim of this study was to assess the effects of C1 esterase inhibitor (C1-INH) on ischemic injury in the rat model of middle cerebral artery suture occlusion and reperfusion.
Thirty-six male Wistar rats were used. Intraluminal middle cerebral artery occlusion was performed for 60 minutes. Just before reperfusion, C1-INH (50 international units/kg) (C1-INH group, n = 19) or saline solution (control group, n = 17) was administered. Physiological parameters (arterial blood gas values, mean arterial blood pressure, and heart rate) and local cerebral blood flow were recorded during the experiment. Forty-eight hours after reperfusion, all rats were killed, and assessments of leukocyte infiltration with a myeloperoxidase activity assay and histological analyses with 2,3,5-triphenyl tetrazolium chloride staining were performed.
The physiological parameters and local cerebral blood flow values were not significantly different in the two groups. The infarction volume was significantly smaller and the myeloperoxidase activity was significantly lower in the C1-INH group (84.9 +/- 69.1 mm(3) and 0.40 +/- 0.29 units/g, respectively) than in the control group (202.3 +/- 98.3 mm(3) and 1.41 +/- 0.44 units/g, respectively) (P < 0.01). Myeloperoxidase activities were strongly correlated with infarction volumes (r = 0.73, P < 0.01).
The results of this study indicated that C1-INH reduced polymorphonuclear leukocyte accumulation and neuronal damage in focal ischemia and reperfusion.