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). Conclusion: 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. La thrombine cause une atrophie neuronale et une mort cellulaire aiguë mais ne cause pas de mort cellulaire chronique. Contexte: De nombreuses variables contribuent, parfois d’une manière essentielle, à l’étendue des effets au cerveau à la suite d’une hémorragie intra-cérébrale (HIC). Notamment la production de thrombine, nécessaire pour arrêter le saignement, provoque également la mort cellulaire aiguë et l'œdème. Dans certains modèles d’HIC du rongeur, les neurones péri- hématomes meurent au cours des semaines. Par conséquent nous avons évalué si la thrombine est responsable de la dégénérescence chronique. Des déficiences fonctionnelles suivant une HIC entraînent également des effets sublétaux chez les neurones, surtout la perte des dendrites. Ainsi nous avons testé si la thrombine seule cause un effet s