TY - JOUR
T1 - Acute Splenic Irradiation Reduces Brain Injury in the Rat Focal Ischemic Stroke Model
AU - Ostrowski, Robert P.
AU - Schulte, Reinhard W.
AU - Nie, Ying
AU - Ling, Ted
AU - Lee, Timothy
AU - Manaenko, Anatol
AU - Gridley, Daila S.
AU - Zhang, John H.
N1 - Funding Information:
Acknowledgments This work was supported by grants NS43338 and HD43120 from the National Institutes of Health to JH Zhang.
PY - 2012/12
Y1 - 2012/12
N2 - Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-h middle cerebral artery occlusion, then CT-scanned for spleen localization, and irradiated to the lateral splenic region with 8 Gy of Cobalt-60 at 3, 4, 6, or 8 h after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia, the rats were euthanized, and the brains, recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 h reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 h after start of ischemia significantly reduced cerebral infarction volumes measured at 48 h and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 h. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 h offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. © 2012 Springer Science+Business Media, LLC.
AB - Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-h middle cerebral artery occlusion, then CT-scanned for spleen localization, and irradiated to the lateral splenic region with 8 Gy of Cobalt-60 at 3, 4, 6, or 8 h after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia, the rats were euthanized, and the brains, recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 h reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 h after start of ischemia significantly reduced cerebral infarction volumes measured at 48 h and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 h. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 h offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. © 2012 Springer Science+Business Media, LLC.
KW - Cerebral ischemia
KW - Cobalt-60
KW - Lymphocyte
KW - Neuroinflammation
KW - Rats
KW - Spleen
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U2 - 10.1007/s12975-012-0206-5
DO - 10.1007/s12975-012-0206-5
M3 - Article
SN - 1868-4483
VL - 3
SP - 473
EP - 481
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 4
ER -