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

Background and Purpose-Extravasation of blood is associated with intracerebral hemorrhage and head trauma. The mechanism of brain cell injury associated with hemorrhage differs from that due to pure ischemia. The purpose of this study was to investigate the acute changes after intracerebral injections 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 plasminogen activator, low- (0.05 U/5 muL) and high-dose (0.5 U/5 muL) plasminogen, and low- (0.335 U/5 muL) and high-dose (3.35 U/5 muL) plasmin. Forty-eight hours later rats were perfusion fixed. Brain damage area, eosinophilic neurons, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells, infiltrating neutrophils, CD8a immunoreactive leukocytes, and reactive microglia were quantified. Results-Damage area in striatum, dying cells, inflammatory cells, and microglial reaction were significantly greater after the high-dose plasminogen, plasmin, and thrombin injections. Tissue plasminogen activator injections were associated with mild inflammation. Conclusions-These results suggested that thrombin and plasmin are harmful to brain cells in vivo. Although the doses required to cause damage are relatively great in consideration of the plasma content of these proteins, their pathological effect might be enhanced through synergism with other mechanisms.