Comparison of brain cell death and inflammatory reaction in three models of intracerebral hemorrhage in adult rats☆
Section snippets
Animal preparation
All experimental procedures were done in accordance with the guidelines of the Canadian Council on Animal Care. Protocols were approved by the local experimental ethics committee.
Autologous whole blood-induced ICH
Twenty-five young adult male Sprague-Dawley rats weighing between 175 and 250 grams were used. Each rat was anesthetized intraperitoneally with pentobarbital (50 mg/kg) and placed in a stereotactic frame (David Kopf Instruments, Tujunga, CA). A midline scalp incision was made and a hole was drilled in the skull (3 mm
Results
All rats tolerated the surgical procedure well, and there was no surgical mortality. In all groups, the damaged brain cells surrounding the hematoma appeared pale on H&E stain because of edema and/or necrosis. Following autologus whole blood injection, the irregular hematoma core was located in striatum (Fig 1a), although there was extension into the adjacent white matter in approximately 25% of the rats. Following collagenase injection, the hematoma core was more spherical; it was
Discussion
ICH causes brain damage through multiple mechanisms. Direct tissue destruction by the hemorrhagic event and dissection of blood along tissue planes occurs immediately. This is followed by development of edema and secondary ischemic damage caused by raised intracranial pressure and distortion of the microvasculature. Delayed damage could result through a variety of mechanisms, including local ischemia, the release of toxins by blood breakdown products, thrombin release, or inflammatory cell
Acknowledgements
We thank Dr. Huijin Yan for assistance with the collagenase animal model.
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Supported by grants from the Heart and Stroke Foundation of Manitoba, Manitoba Health Research Council, and Children’s Hospital Foundation to M.R.D. He also holds the Manitoba Medical Services Foundation Clinical Research Professorship. M.X. has a Doctoral Research Award from the Canadian Institutes of Health Research/Heart and Stroke Foundation of Canada.