Thrombin Causes Neuronal Atrophy and Acute but not Chronic Cell Death.
BACKGROUND
Brain injury after intracerebral hemorrhage (ICH) arises from numerous contributors, of which some also play essential roles. Notably, thrombin production, needed to stop bleeding, also causes acute cell death and edema. In some rodent models of ICH, peri-hematoma neurons die over weeks. Hence we evaluated whether thrombin is responsible for this chronic degeneration. Functional impairments after ICH also result from sub-lethal damage to neurons, especially the loss of dendrites. Thus, we evaluated whether thrombin infusion alone, a reductionist model of ICH, causes similar injury.


METHODS
Adult rats had a modest intra-striatal infusion of thrombin (1 U) or saline followed by a behavioral test, to verify impairment, 7 days later. After this they were euthanized and tissue stained with Golgi-Cox solution to allow the assessment of dendritic morphology in striatal neurons. In a second experiment, rats survived 7 or 60 days after thrombin infusion in order to histologically determine lesion volume.


RESULTS
Thrombin caused early cell death and considerable atrophy in surviving peri-lesion neurons, which had less than half of their usual numbers of branches. However, total tissue loss was comparable at 7 (24.1 mm3) and 60 days (25.6 mm3).


CONCLUSIONS
Thrombin infusion causes early cell death and neuronal atrophy in nearby surviving striatal neurons but thrombin does not cause chronic tissue loss. Thus, the chronic degeneration found after ICH in rats is not simply and solely due to acute thrombin production. Nonetheless, thrombin is an important contributor to behavioral dysfunction because it causes cell death and substantial dendritic injury.
1Center for Neuroscience,University of Alberta,Edmonton,Alberta.
Jayalakshmi
J
Caliaperumal
2Department of Psychology,University of Alberta,Edmonton,Alberta.
Sonia
S
Brodie
2Department of Psychology,University of Alberta,Edmonton,Alberta.
Yonglie
Y
Ma
1Center for Neuroscience,University of Alberta,Edmonton,Alberta.
Frederick
F
Colbourne
D000818:Animals; D001284:Atrophy / Q000139:chemically induced* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000473:pathology; D057967:Infusions, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000008:administration & dosage* / Q000633:toxicity*
D013917:Thrombin