Abstract
Splenectomy before or immediately after stroke provides early brain protection. This study aims to explore the effect of splenectomy on long-term neurological recovery after stroke, which is currently lacking in the field. Adult male rats were randomized into splenectomy or sham groups and then subjected to 90 min of middle cerebral artery occlusion (MCAO). Spleen was removed right upon reperfusion or 3d after MCAO. Infarct volume, neurological functions, and peripheral immune cell populations were assessed up to 28d after stroke. The results show that delayed removal of spleen did not reduce brain tissue loss and showed no effect on sensorimotor function (Rotarod, beam balance, forelimb placing, grid walk, and adhesive removal tests) or cognitive function (Morris water maze). Spleen removal immediately upon reperfusion, although significantly reduced the infarct size and immune cell infiltration 3d after MCAO, also failed to promote long-term recovery. Flow cytometry analysis demonstrated that immediate splenectomy after MCAO resulted in a prolonged decrease in the percentage of CD3+CD4+ and CD3+CD8+ T cells in total lymphocytes as compared to non-splenectomy MCAO rats. In contrast, the percentage of CD3-CD45RA+ B cells was significantly elevated after splenectomy. As a result, the ratio of T/B cells was significantly reduced in stroke rats with splenectomy. In conclusion, delayed splenectomy failed to provide long-term protection to the ischemic brain or improve functional recovery. The acute neuroprotective effect achieved by early splenectomy after stroke cannot last for long term. This loss of neuroprotection might be related to the prolonged disturbance in the T cell to B cell ratio.
Highlights
Immune responses, which play a pivotal role in vascular aging and in the progress of brain injuries, are activated soon after ischemic stroke [1, 2]
These data demonstrated that delayed splenectomy resulted in comparable infarct volume in splenectomy and non-splenectomy rats after middle cerebral artery occlusion (MCAO)
The present study explored the effect of splenectomy on long-term outcomes after ischemic stroke
Summary
Immune responses, which play a pivotal role in vascular aging and in the progress of brain injuries, are activated soon after ischemic stroke [1, 2]. While the T lymphocytes were shown to play a detrimental role in ischemia/reperfusion injury [7, 9], the B lymphocytes seemed to be protective after acute stroke [10]. Adding to this complexity, accumulating evidence suggested the beneficial effects of regulatory immune cells, including regulatory T cells (Treg) [11,12,13] and regulatory B cells [10, 14, 15] in the ischemic brain. The prolonged change in the T cell to B cell ratio after spleen removal was observed in stroke rats, which might be related to the loss of protection in the long term
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