Acute tissue damage after injections of thrombin and plasmin into rat striatum

Background and Purpose-Extravasation of blood is associated with intracereb ral hemorrhage and head trauma. The mechanism of brain cell injury associat ed with hemorrhage differs from that due to pure ischemia. The purpose of t his study was to investigate the acute changes after intracerebral injectio ns of proteins that are involved in blood clotting and clot lysis. Methods-Sixty-eight adult rats were subjected to stereotaxic intrastriatal injections of normal saline (5 muL), low- (2.5 U/5 muL) and high-dose (25 U /5 muL) thrombin, low- (0.1 mug/5 muL) and high-dose (1 mug/5 muL) tissue p lasminogen activator, low- (0.05 U/5 muL) and high-dose (0.5 U/5 muL) plasm inogen, and low- (0.335 U/5 muL) and high-dose (3.35 U/5 muL) plasmin. Fort y-eight hours later rats were perfusion fixed. Brain damage area, eosinophi lic neurons, terminal deoxynucleotidyl transferase-mediated deoxyuridine tr iphosphate-biotin nick end labeling (TUNEL)-positive cells, infiltrating ne utrophils, CD8a immunoreactive leukocytes, and reactive microglia were quan tified. Results-Damage area in striatum, dying cells, inflammatory cells, and micro glial reaction were significantly greater after the high-dose plasminogen, plasmin, and thrombin injections. Tissue plasminogen activator injections w ere associated with mild inflammation. Conclusions-These results suggested that thrombin and plasmin are harmful t o brain cells in vivo. Although the doses required to cause damage are rela tively great in consideration of the plasma content of these proteins, thei r pathological effect might be enhanced through synergism with other mechan isms.