Thrombin attenuation is neuroprotective in the injured rat optic nerve.
The functional loss that often follows injury of the mammalian CNS has been attributed not only to the immediate neural loss, but also to secondary neuronal degeneration caused by toxic biochemical mediators in the environment of the injured nerve. We report here that a high thrombin content, produced as a result of injury-induced activation of prothrombin, appears to be an important mediator of secondary damage. Measurement of post-traumatic neuronal survival in vivo revealed that post-traumatic local application of the thrombin inhibitor N-alpha-(2-naphthylsulphonylglycyl)-4-(D,L)-amidinophenylalanine piperidide acetate in the rat optic nerve subjected to mild partial crush injury left twice as many retinal ganglion cells with functioning axons as in controls. Thus, by readjusting thrombin activity, thereby possibly obtaining a moderate post-traumatic increase and thus gaining the benefit of thrombin without its toxic effects, it may be possible to create an environment that is more favourable for post-traumatic survival.
Friedmann
I
I
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Yoles
E
E
Schwartz
M
M
D000287:Administration, Topical; D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D009900:Optic Nerve / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000150:complications / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000378:metabolism
D000991:Antithrombins; D004151:Dipeptides; D018696:Neuroprotective Agents; D010880:Piperidines; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D011516:Prothrombin; D013917:Thrombin