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Astrocytic Tissue Factor Plays An Important Role In Regulation Of CSF Circulation And Control Of Blood Spread Following Subarachnoid Hemorrhage
Author(s) -
Golanov Eugene,
Bovshik Evgueni,
Foster Chase,
Zhang Jonathan,
Wong Kelvin,
Wong Stephen,
Britz Gavin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb636
Subject(s) - subarachnoid hemorrhage , cisterna magna , subarachnoid space , medicine , cerebrospinal fluid , cistern , perforation , circle of willis , vasospasm , cisterna , anatomy , pathology , biology , materials science , genetics , archaeology , metallurgy , cell , punching , history , golgi apparatus
Rupture of cerebral aneurysm leads to blood accumulation within the subarachnoid space, known as a subarachnoid hemorrhage. Fatality resulting from acute subarachnoid hemorrhage (SAH) reaches 50%. Volume of blood entering subarachnoid space (SS) following aneurism rupture is one of the leading factors determining the outcome. Retardation of cerebrospinal fluid (CSF) flow emerges as one of the key mechanisms limiting spread of blood in SS. It has been established that following SAH CSF flow is significantly reduced. We hypothesize that tissue factor (TF), the key factor of extrinsic pathway of coagulation cascade expressed by brain astrocytes, plays a critical role in reduction of CSF and localization of the hemorrhage following SAH. Perforation model of SAH was used in C57BL mice. We monitored changes of CSF flow by injecting fluorescent microspheres (0.02 um, FM) in cisterna magna (CM) from 1 hour to 30 days following SAH. We injected intracerebro ventricularly TF antibodies or IgG one hour before the perforation to explore role of TF in spread of blood across the SS and CSF flow. In naive and sham (no perforation) mice FM injected into CM filled ventral cisterns and spread along the perivascular space of Willis circle and middle cerebral arteries (MCA) reaching the olfactory bulbs within 1 hr. Following perforation of Willis circle, blood spread along the paravascular space, ventral cisterns and proximal trunk of ipsilateral MCA. FM injected into CM following SAH, were confined to the caudal ventral cisterns limited by the rostral pons border. CSF flow remained impeded for up to 30 days. The spread of hemorrhage did not correlate with the degree of CSF flow retardation. Block of TF by specific antibodies lead to significant (p<0.05) expansion of hemorrhage by 95%. In non‐SAH animals, intraventricular administration of TF antibodies significantly increased spread of CM injected FM compared to their spread following IgG administration (p<0.05). Subsequent immunohistochemistry demonstrated substantial association of TF with glia limitans, especially on the ventral brain surface. We conclude that TF plays an important role in localization of blood spread following arterial perforation. Moreover, block of TF by specific antibodies significantly facilitates spread of FM injected into CM allowing speculating that TF may play a regulatory role in CSF flow. It was suggested that astrocytes are the only source of TF in brain. We propose that astrocytes may exercise their CSF flow regulatory function and limit the blood spread through TF‐dependent mechanism. Support or Funding Information Oden Foundation