CEREBRAL SINUS AND VENOUS THROMBOSIS IN RATS INDUCES LONG-TERM DEFICITS IN BRAIN-FUNCTION AND MORPHOLOGY - EVIDENCE FOR A CYTOTOXIC GENESIS

The pathophysiology of cerebral venous infarctions is poorly understoo d, due partially to the lack of a suitable experimental model. Therefo re, we developed a model in rats to study acute and long-term changes of brain function and morphology following thrombosis of the superior sagittal sinus. The superior sagittal sinus of rats was exposed, ligat ed, and injected with thrombogenic material. Thrombosis of the longitu dinal sinus and ascending cortical veins was monitored by intravital f luorescence angiography. Histology was studied at 24 h and 4 weeks aft er thrombosis and changes in intracranial pressure, electroencephalogr am (EEG), and tissue impedance were noted. Spontaneous locomotor activ ity was followed for 4 weeks after thrombosis. The effect of heparin t reatment on tissue impedance was evaluated. Thrombosis of the superior sagittal sinus could be regularly induced, although pathological sequ elae developed only if ascending veins were affected. Sinus and venous thrombosis was histologically characterized by bilateral, parasagitta l infarctions. Thrombosis induction was followed by an increase in int racranial pressure from 4.7 +/- 1.6 to 12.8 +/- 2.4 mm Hg (n = 4) at 1 h after thrombosis, associated with an exponential rise in tissue imp edance to 165 +/- 14% (n = 8) of the control. EEG changes were similar to those following global cerebral ischemia and remained pathological for up to 6 months after thrombosis (n = 6). As a permanent behaviora l deficit spontaneous locomotor activity was reduced to 60 +/- 10% (n = 6) of the control. Finally, the administration of heparin (1 IU/g bo dy weight) after thrombosis induction was found to reverse the patholo gical tissue impedance response of the brain. In conclusion, involveme nt of ascending cortical veins following sinus thrombosis appears to b e critical for the development of irreversible tissue damage, such as infarction. Changes in intracranial pressure and tissue impedance sugg est that the venous thrombosis was followed by brain edema of a predom inantly cytotoxic nature. Venous thrombosis led to long-term changes o f brain function, as demonstrated by persistent disturbances of the EE G or of the spontaneous locomotor drive. These deficits may be amenabl e to treatment with heparin.