title: Intracisternal administration of tissue plasminogen activator improves cerebrospinal fluid flow and cortical perfusion after subarachnoid hemorrhage in mice.
abstract: Early brain injury (EBI) during the first 72 h after subarachnoid hemorrhage (SAH) is an important determinant of clinical outcome. A hallmark of EBI, global cerebral ischemia, occurs within seconds of SAH and is thought to be related to increased intracranial pressure (ICP). We tested the hypothesis that ICP elevation and cortical hypoperfusion are the result of physical blockade of cerebrospinal fluid (CSF) flow pathways by cisternal microthrombi. In mice subjected to SAH, we measured cortical blood volume (CBV) using optical imaging, ICP using pressure transducers, and patency of CSF flow pathways using intracisternally injected tracer dye. We then assessed the effects of intracisternal injection of recombinant tissue plasminogen activator (tPA). ICP rose immediately after SAH and remained elevated for 24 h. This was accompanied by a decrease in CBV and impaired dye movement. Intracisternal administration of tPA immediately after SAH lowered ICP, increased CBV, and partially restored CSF flow at 24 h after SAH. Lowering ICP without tPA, by draining CSF, improved CBV at 1 h, but not 24 h after SAH. These findings suggest that blockade of CSF flow by microthrombi contributes to the early decline in cortical perfusion in an ICP-dependent and ICP-independent manner and that intracisternal tPA may reduce EBI and improve outcome after SAH.
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, 3181 S.W. Sam Jackson Pk. Rd., UHN-2, Portland, OR, 97239-3098, USA.
authors: Dominic A
authors: DA
authors: Siler
authors: Jorge A
authors: JA
authors: Gonzalez
authors: Ruikang K
authors: RK
authors: Wang
authors: Justin S
authors: JS
authors: Cetas
authors: Nabil J
authors: NJ
authors: Alkayed
mesh_terms: D000818:Animals; D002555:Cerebrospinal Fluid / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D007427:Intracranial Pressure / Q000187:drug effects*; D051379:Mice; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010959:Tissue Plasminogen Activator