title: 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.
authors.affiliation: Department of Neurology, Caritasklinikum Saarbruecken, St. Theresia, Rheinstrasse 2, 66113, Saarbruecken, Germany, erwin.stolz@neuro.med.uni-giessen.de.
authors.forename: Erwin
authors.initials: E
authors.lastname: Stolz
authors.forename: Andrea
authors.initials: A
authors.lastname: Fett
authors.forename: Carina
authors.initials: C
authors.lastname: Wessels
mesh_terms: D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002712:Chlorides / Q000633:toxicity; D003097:Collateral Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D017984:Enoxaparin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005169:Factor VIII / Q000032:analysis; D005290:Ferric Compounds / Q000633:toxicity; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D018810:Magnetic Resonance Angiography; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D015588:Observer Variation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015424:Reperfusion; D012851:Sinus Thrombosis, Intracranial / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D054063:Superior Sagittal Sinus / Q000187:drug effects / Q000473:pathology*; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D002712:Chlorides; D017984:Enoxaparin; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D005904:Glial Fibrillary Acidic Protein; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; D005169:Factor VIII; D010959:Tissue Plasminogen Activator; C024555:ferric chloride; D000077284:Abciximab