Abstract 128: Intracisternal Administration of Tissue Plasminogen Activator Improves Cerebrospinal Fluid Flow and Cortical Perfusion After Subarachnoid Hemorrhage in Mice
Early brain injury (EBI) during the first 72 hours after subarachnoid hemorrhage (SAH) is a key 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 after SAH 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 recombinant tissue plasminogen activator (tPA). ICP rose immediately after SAH and remained elevated for 24 hours. This was accompanied by decreased CBV and impaired dye movement. Intracisternal administration of tPA immediately after SAH lowered ICP (from 34.8 ± 3.7 (n=5) to 17.5 ± 3.1 mmHg, (n=6)), increased CBV (from 51.5 ± 8.9 (n=5) to 80 ± 4.7 % of baseline, (n = 6)) and partially restored CSF flow at 24 hours after SAH. Lowering ICP without tPA, by draining CSF, improved CBV at 1, but not 24 hours. These findings suggest that blockade of CSF flow by microthrombi contributes to the early decline in cortical perfusion in an ICP-dependent and independent manner, and that intracisternal tPA may reduce EBI and improve outcome after SAH.
Figure 1. tPA reduces ICP and improves perfusion after SAH. A) Representative perfusion images of the cortex at baseline, 1h post SAH/sham (pre-treatment), and 24h post-SAH/Sham (post-treatment). B) ICP at 1h pre-treatment and 24h post-treatment. C) Quantification of perfused CBV 1h pre-treatment and 24h post-treatment. Sham (n =3), SAH vehicle (n =5), SAH tPA (n = 6) * = P <0.05 Scale bar = 500 um
Author Disclosures: D.A. Siler: Research Grant; Significant; F30 HL108624. J.A. Gonzalez: None. R.K. Wang: Research Grant; Significant; R01 HL093140, R01 EB009682. J.S. Cetas: None. N.J. Alkayed: Research Grant; Significant; R01 NS044313, NS070837.
- © 2014 by American Heart Association, Inc.