Tissue-type plasminogen activator has paradoxical roles in focal cerebral ischemic injury by thrombotic middle cerebral artery occlusion with mild or severe photochemical damage in mice.
The role of endogenous tissue-type plasminogen activator (tPA) in focal cerebral ischemic injury (FCII) after middle cerebral artery occlusion was studied using tPA gene-deficient (KO) mice and their wild-type (WT) littermates. The middle cerebral artery was occluded by thrombi induced by three different intensities of photochemical damage, a method that was newly introduced in mice. In both WT and KO mice, the intensity-dependent increase of FCII size was observed. The FCII size in tPA WT mice was smaller than in KO mice in cases of mild damage, whereas the FCII size was larger in WT mice than in KO mice in cases of severe damage. There was no difference in FCII size between WT and KO mice in cases of moderate damage. The number of microthrombi also increased with damage intensity in both WT and KO mice, but was less in WT mice at all intensities of damage. The results support the validity of the model of thrombotic occlusion by photochemical damage in mice, and suggest that endogenous tPA protects FCII through thrombolytic action on transient occlusion of middle cerebral artery with mild damage, but deteriorates on persistent occlusion with severe damage.
Nagai
Nobuo
N
Department of Physiology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Zhao
Bing-Qiao
BQ
Suzuki
Yasuhiro
Y
Ihara
Hayato
H
Urano
Tetsumei
T
Umemura
Kazuo
K
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000032:analysis; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D020767:Intracranial Thrombosis / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010777:Photochemistry; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000378:metabolism*
D005340:Fibrinogen; D010959:Tissue Plasminogen Activator