Acute Splenic Irradiation Reduces Brain Injury in the Rat Focal Ischemic Stroke Model

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.