Cell injury leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. Here, we demonstrate that natural extracellular RNA as well as artificial RNA (poly- I IntroductionBrain homeostasis is maintained by the blood-brain barrier (BBB), which forms a mechanical and functional threshold between the central nervous system and the systemic circulation. The barrier is relatively impermeable to ions, many amino acids, small peptides, and proteins, and thus contributes to the maintenance of a specific neural tissue environment. In vertebrates, the BBB exists at the level of the endothelial cells that form brain capillaries 1 in order to regulate and limit the degree of trans-and paracellular flux. 2 The tight barrier properties of the BBB result from the absence of fenestrations, the low number of pinocytotic vesicles, and the presence of tight intercellular junctions between endothelial cells with extremely high electrical resistance. 3 Pathologic conditions associated with brain tumors, head injury, or ischemic stroke are accompanied by endothelial-cell dysfunction, leading to increased permeability across the BBB, which might lead to the development of vasogenic cerebral edema. 4,5 Vascular endothelial growth factor (VEGF) as a hypoxia/ischemia inducible protein in vitro and in vivo is one of the strongest natural permeability factors 6 and a likely candidate for the development of ischemia-and tumor-induced vasogenic brain edema. 7-9 VEGF stimulates endothelial-cell growth and migration in vitro 10,11 and angiogenesis in vivo. 6,12 VEGF was originally described as a potent vascular permeability factor responsible for the accumulation of plasma protein-rich fluid in the ascites of patients with tumors. 13 Structurally, VEGF exists as a dimeric glycoprotein of molecular weight (Mr) 34 000 to 42 000 and is related to the platelet-derived growth factor family of molecules. 14 Although VEGF is the product of a single gene, 6 differentially spliced isoforms between 121 and 206 amino acid residues exist in humans 15,16 that exhibit similar functional activities. Different isoforms are distinguished by their affinity for heparin: although VEGF 121 does not bind heparin, VEGF 165 has moderate affininity for heparin, whereas VEGF 189 and VEGF 206 bind heparin with high affinity. 17 VEGF exerts its multiple actions by ligation with tyrosine kinase receptors, VEGFreceptor 1 (VEGF-R1), as well as VEGF-R2, [18][19][20] which are expressed on vascular endothelial cells. A third member, VEGF-R3 is expressed on lymphatic endothelial cells. 21 During pathologic conditions of the brain associated with tumor burden, stroke, or head injury, nucleic acids might be released by damaged cells. RNA-proteolipid complexes were detected in the circulation of patients with cancer and were suggested to represent a specific secretory product of cancer cells. 22 Accordingly, circulating RNA is present in blood plasma of patients with tumors. 23 The presence of specific types ...

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.

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