Intracisternal Administration of Tissue Plasminogen Activator Improves Cerebrospinal Fluid Flow and Cortical Perfusion After Subarachnoid Hemorrhage in Mice

Dominic A. Siler, Jorge A. Gonzalez, Ruikang K. Wang, Justin Cetas, Nabil Alkayed

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)227-237
Number of pages11
JournalTranslational Stroke Research
Volume5
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Tissue Plasminogen Activator
Subarachnoid Hemorrhage
Intracranial Pressure
Cerebrospinal Fluid
Perfusion
Blood Volume
Brain Injuries
Coloring Agents
Pressure Transducers
Intracranial Hypertension
Optical Imaging
Brain Ischemia
Injections

Keywords

  • Cerebral blood flow
  • Early brain injury
  • Global ischemia
  • Intracranial pressure
  • Subarachnoid hemorrhage
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

Cite this

Intracisternal Administration of Tissue Plasminogen Activator Improves Cerebrospinal Fluid Flow and Cortical Perfusion After Subarachnoid Hemorrhage in Mice. / Siler, Dominic A.; Gonzalez, Jorge A.; Wang, Ruikang K.; Cetas, Justin; Alkayed, Nabil.

In: Translational Stroke Research, Vol. 5, No. 2, 2014, p. 227-237.

Research output: Contribution to journalArticle

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