Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus.
Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was studied in ischemia-related hippocampal neuronal death and compared with a low molecular weight of heparin, named dalteparin in rats. Transient global ischemia was produced by four vessel-occlusion, the occlusion of the bilateral common carotid arteries following the electrocautherization of the vertebral arteries. 3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after 7min-occlusion/reperfusion. Seven days after the operation, the animals were perfused with 4% paraformaldehyde, and paraffinized coronal brain sections measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal damage was then estimated as a ratio of the number of degenerated neurons to that of both the surviving and degenerated neurons in three distinct area of the CA1 subfield. The ratio of neuronal death increased with the length of the occlusion-time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the neuronal damage induced by 7min-occlusion. These results demonstrated that both PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion-induced damage thus suggesting that they may be potentially useful therapeutic agents for acute ischemic stroke.
Sakurai-Yamashita
Yasuko
Y
Department of Pharmacology 1, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. yasukosy@net.nagasaki-u.ac.jp
Kinugawa
Hidekazu
H
Niwa
Masami
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D017536:Carotid Artery, Common / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D017985:Dalteparin / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D018696:Neuroprotective Agents; D010426:Pentosan Sulfuric Polyester; D017985:Dalteparin