Thrombin inhibition attenuates neurodegeneration and cerebral edema formation following transient forebrain ischemia.
The disturbance of microcirculation following cerebral ischemia leads to an enlargement of cerebral infarct volume. Endogenous thrombin may play a role in this disturbance of microcirculation following cerebral ischemia. Therefore, the inhibition of thrombin may improve neurodegeneration and the accumulation of cerebral edema following cerebral ischemia in gerbils. The effects of thrombin inhibitor (argatroban) on cerebral ischemia were investigated in comparison with thromboxane A2 synthase inhibitor (ozagrel) and cyclooxygenase inhibitor (aspirin) following bilateral common carotid artery occlusion and reperfusion (CCA:O/R) in male Mongolian gerbils. This study consisted of three experiments: (1) morbidity and survival ratio (n=40 for each), (2) histopathology (n=12 for each), and (3) mean arterial blood pressure, local cerebral blood flow (CBF), and cerebral specific gravity (n=8 for each). Argatroban treatment improved survival ratio and stroke index, and decreased ischemically injured cell numbers in cortex and hippocampus and cerebral edema in cortex compared with aspirin and saline, in concert with the fast recovery of local CBF without reactive hyperemia following bilateral CCA:O/R. Ozagrel treatment also improved those factors compared with saline, in concert with the fast recovery of local CBF with reactive hyperemia. Aspirin treatment improved survival ratio and stroke index, and decreased ischemically injured cell numbers in cortex. Thrombin inhibition with argatroban decreases neurodegeneration and cerebral edema following bilateral CCA:O/R in gerbils.
Ohyama
H
H
Second Department of Internal Medicine, Division of Stroke and Atherosclerosis, Kagawa Medical University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, 761-0793, Kagawa, Japan.
Hosomi
N
N
Takahashi
T
T
Mizushige
K
K
Kohno
M
M
D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010875:Pipecolic Acids / Q000494:pharmacology; D013449:Sulfonamides; D015996:Survival Rate; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000991:Antithrombins; D005343:Fibrinolytic Agents; D008689:Methacrylates; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban; C034364:ozagrel; D001241:Aspirin