Histopathological effects of different therapy strategies in experimental sinus thrombosis

Abstract

The optimal treatment for cerebral venous thrombosis is still under debate. The histological consequences of different treatments have not been systematically studied and may be of value in this debate. Thrombosis of the superior sagittal sinus was induced in rats by topical application of ferric chloride. Animals were treated 6 h after operation with subcutaneous injection of 450 IU/kg enoxaparin twice daily (n = 10), with 10 mg recombinant tissue plasminogen activator (rt-PA)/kg (n = 12), and with 6 mg abciximab/kg (n = 10). Eleven animals were treated with saline (controls), and four animals were sham-operated without thrombosis induction. Animals were killed on day 7. Coronal brain slices were stained with hematoxylin-eosin (HE) and against glial fibrillary acidic protein (GFAP), and factor VIII. Histology was quantified in parasagittal and temporal regions of interest. Compared with controls, counts of pyknotic neurons on HE stain were significantly lower in the enoxaparin group. Counts for GFAP-expressing astrocytes were highest in the enoxaparin (p < 0.001) and rt-PA (p < 0.05)-treated groups. Angiogenesis defined as factor VIII-expressing vessels was significantly (p < 0.01) higher in the enoxaparin and significantly lower (p < 0.01) in the rt-PA group compared with controls. In this animal model, we found histological differences related to the different treatments, which cannot be explained by recanalization and its speed alone.