Ischemic brain tissue water content: CT monitoring during middle cerebral artery occlusion and reperfusion in rats.

PURPOSE To prospectively perform computed tomography (CT) in rats to determine whether ischemic edema can be reversed by using early arterial reperfusion. MATERIALS AND METHODS This study was approved by the local animal protection committee. A suture model was used to occlude the right middle cerebral artery (MCA) in rats for 1, 2, 3, or 4 hours. X-ray attenuation of the brain was measured directly before reperfusion and repeatedly during reperfusion for up to 24 hours. Infarct volumes were determined with triphenyltetrazolium chloride staining. Means of attenuation and infarct volume were compared between hemispheres and groups with a paired t test and analysis of variance. Mixed linear models were applied to compare attenuation among groups over time. RESULTS During MCA occlusion, attenuation decreased to 69.3 HU +/- 1.9 (standard deviation) after 1 hour (n=12), 66.6 HU +/- 2.0 after 2 hours (n=10), 65.4 HU +/- 2.9 after 3 hours (n=11), and 64.1 HU +/- 1.8 after 4 hours (n=9) (P<.0001). After reperfusion, attenuation remained stable in the 1-hour occlusion group (P=.16) but further and steadily declined in the 2-, 3-, and 4-hour occlusion groups (P<.001). Attenuation during reperfusion in the 1-hour occlusion group differed significantly from that in the 2-, 3-, and 4-hour occlusion groups. CONCLUSION CT is able to help monitor ischemic edema after MCA occlusion and reperfusion. Ischemic brain edema was not consistently reversible with reperfusion, even after 1 hour of occlusion, and further increased with reperfusion induced at 2 hours or later.

[1]  L Bozzao,et al.  Early prediction of irreversible brain damage after ischemic stroke at CT. , 2001, Radiology.

[2]  P. Weinstein,et al.  Edema, Cation Content, and ATPase Activity After Middle Cerebral Artery Occlusion in Rats , 1992, Stroke.

[3]  Michael Forsting,et al.  Brain Tissue Water Uptake after Middle Cerebral Artery Occlusion Assessed with CT , 2004, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[4]  L. G. Mitchell,et al.  Serial measurements of CT attenuation and specific gravity in experimental cerebral edema. , 1980, Radiology.

[5]  Weili Lin,et al.  Temporal Relationship Between Apparent Diffusion Coefficient and Absolute Measurements of Cerebral Blood Flow in Acute Stroke Patients , 2003, Stroke.

[6]  F J Schuier,et al.  Experimental Brain Infarcts in Cats: II. Ischemic Brain Edema , 1980, Stroke.

[7]  C. Truwit,et al.  Loss of the insular ribbon: another early CT sign of acute middle cerebral artery infarction. , 1990, Radiology.

[8]  M. Gado,et al.  Water content and water structure in CT and MR signal changes: possible influence in detection of early stroke. , 1988, AJNR. American journal of neuroradiology.

[9]  K. Kogure,et al.  Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. , 1989, Stroke.

[10]  U. Ito,et al.  Brain Edema During Ischemia and After Restoration of Blood Flow Measurement of Water, Sodium, Potassium Content and Plasma Protein Permeability , 1979, Stroke.

[11]  R. Zimmerman Stroke wars: episode IV CT strikes back. , 2004, AJNR. American journal of neuroradiology.

[12]  R. Knab,et al.  Cerebral perfusion impairment correlates with the decrease of CT density in acute ischaemic stroke , 2004, Neuroradiology.

[13]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[14]  B. Siesjö,et al.  Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat , 2004, Experimental Brain Research.

[15]  F. Shishido,et al.  Early CT finding in cerebral infarction: obscuration of the lentiform nucleus. , 1988, Radiology.

[16]  Y Wang,et al.  Brain tissue sodium is a ticking clock telling time after arterial occlusion in rat focal cerebral ischemia. , 2000, Stroke.

[17]  P. Picozzi,et al.  Reperfusion after cerebral ischemia: influence of duration of ischemia. , 1986, Stroke.

[18]  Michael D Hill,et al.  Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis: Prognostic Value of the Alberta Stroke Program Early CT Score in ECASS II , 2006, Stroke.

[19]  K. Takakura,et al.  Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin. , 1985, Stroke.

[20]  W. Kuschinsky,et al.  Capillary perfusion during incomplete forebrain ischemia and reperfusion in rat brain. , 1993, The American journal of physiology.

[21]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[22]  L Bozzao,et al.  Acute stroke: usefulness of early CT findings before thrombolytic therapy. , 1997, Radiology.

[23]  W. Kuschinsky,et al.  Gross Persistence of Capillary Plasma Perfusion after Middle Cerebral Artery Occlusion in the Rat Brain , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  P. Weinstein,et al.  Reversible middle cerebral artery occlusion without craniectomy in rats. , 1989, Stroke.

[25]  Scott Hamilton,et al.  Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials , 2004, The Lancet.

[26]  L. Pitts,et al.  Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. , 1986, Stroke.

[27]  J. Kucharczyk,et al.  Diffusion-Weighted Magnetic Resonance Imaging of Acute Focal Cerebral Ischemia: Comparison of Signal Intensity with Changes in Brain Water and Na+,K+ -ATPase Activity , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  R. Laing,et al.  Middle Cerebral Artery Occlusion Without Craniectomy in Rats: Which Method Works Best? , 1993, Stroke.

[29]  K. Hossmann Viability thresholds and the penumbra of focal ischemia , 1994, Annals of neurology.

[30]  E. Kim,et al.  CT sign of brain swelling without concomitant parenchymal hypoattenuation: comparison with diffusion- and perfusion-weighted MR imaging. , 2005, Radiology.

[31]  R. Russell,et al.  Duration of Ischemia Influences the Development and Resolution of Ischemic Brain Edema , 2022 .