Inflammatory reaction after focal cerebral ischemia in mouse.
BACKGROUND
In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.


METHODS
Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.


RESULTS
Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2 +/- 2.8 per mm(2)), peaked at 48 hours (29.6 +/- 4.8 per mm(2)), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4 +/- 6.1 per mm(2)), peaked at 48 hours (44.4 +/- 16.8 per mm(2)), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4 +/- 1.2 per mm(2)) 12 hours after MCAO, peaked after 48 hours (20.2 +/- 6.3 per mm(2)), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3 +/- 1.7 per mm(2)), peaked after 48 hours (20.9 +/- 8.4 per mm(2)), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111 +/- 0.023 U/g), peaked after 24 hours (0.194 +/- 0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110 +/- 0.032 U/g), peaked after 24 hours (0.210 +/- 0.067 U/g), and remained elevated at 120 hours.


CONCLUSIONS
The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and intensive in the ischemic cortex than in the ischemic basal ganglia.
Wang
Zhi-Qiu
ZQ
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China. zhiqiuwang@yahoo.com
Chen
Xian-Cheng
XC
Yang
Guo-Yuan
GY
Zhou
Liang-Fu
LF
D000818:Animals; D001479:Basal Ganglia / Q000098:blood supply; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation; D007249:Inflammation / Q000209:etiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D020768:Middle Cerebral Artery; D009195:Peroxidase / Q000032:analysis
D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase