Heparin Reduces Neuroinflammation and Transsynaptic Neuronal Apoptosis in a Model of Subarachnoid Hemorrhage

• DOI: 10.1007/s12975-012-0166-9
• Publication Date: 2012-04-13T14:25:34Z
• Authors: J. Marc Simard; Cigdem Tosun; Svetlana Ivanova; David B. Kurland; Caron Hong; Leanne Radecki; Carter Gisriel; Rupal Mehta; David Schreibman; Volodymyr Gerzanich
• Keywords: NeuN

Subarachnoid hemorrhage (SAH) can lead to disabling motor, cognitive, and neuropsychological abnormalities. Part of the secondary injury cerebral tissues associated with SAH is attributable neuroinflammatory response induced by blood. Heparin a pleiotropic compound that reduces inflammatory responses in conditions outside central nervous system. Using model devoid global insult, we evaluated effect delayed intravenous (IV) infusion heparin, at dose does not produce therapeutic anticoagulation, on neuroinflammation, myelin preservation, apoptosis. Adult male rats underwent bilateral stereotactic injections autologous blood (50 μL) into subarachnoid space entorhinal cortex. The were implanted mini-osmotic pumps delivered either vehicle or unfractionated heparin (10 U/kg/h IV) beginning 12 h after SAH. No mechanical hemorrhagic was observed hippocampus. In controls assessed 48 h, robust neuroinflammation adjacent cortex [neutrophils, activated phagocytic microglia, nuclear factor-kappa B, tumor necrosis factor-alpha, interleukin-1beta] neurodegeneration (Fluoro-Jade C staining loss NeuN). hippocampus, muted indicated Iba1-positive, ED1-negative microglia exhibiting an morphology. perforant pathway showed Fluoro-Jade demyelination, granule cells dentate gyrus had pyknotic nuclei, labeled upregulation cleaved caspase-3, consistent transsynaptic Administration significantly reduced We conclude IV low-dose may attenuate adverse effects