Research Article: Splenectomy Fails to Provide Long-Term Protection Against Ischemic Stroke

Date Published: June 1, 2018

Publisher: JKL International LLC

Author(s): Yuanyuan Ran, Zongjian Liu, Shuo Huang, Jiamei Shen, Fengwu Li, Wenxiu Zhang, Chen Chen, Xiaokun Geng, Zhili Ji, Huishan Du, Xiaoming Hu.

http://doi.org/10.14336/AD.2018.0130

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.

Partial Text

The present study explored the effect of splenectomy on long-term outcomes after ischemic stroke. Spleen is the largest secondary lymphoid organ that serves as a storage site for immune cells, as well as a site of hematopoiesis. The movement of spleen-released immune cells into the blood and their subsequent infiltration into the ischemic brain is thought to exacerbate brain damage during acute stages of stroke. Although gender difference may exist [25], majority of animal studies in rodents agree that the inhibition of splenic function prior to or immediately after MCAO is neuroprotective and significantly reduces cerebral inflammation early after stroke [16]. However, whether and how the spleen responses contribute to long-term outcomes after stroke is not clear. Our study fills this gap by showing the effect of splenectomy on structural and functional deficits up to 28 days after ischemic brain injury. In our first experiment, we removed the spleen 3 days after stroke. Such delayed splenectomy had no early protection and no effect on immune cell infiltration early after stroke, and therefore excluded the possible long-term effects that are secondary to the early changes in infarct volume. Our results suggest that such delayed splenectomy had no impact on long-term brain tissue loss or functional outcomes after stroke. Interestingly, even when spleen was removed immediately after stroke, the reduction in brain infarct could only be observed at early stage after ischemia, which is accompanied by reduced immune cell infiltration. In other words, inhibition of peripheral immune responses by immediate spleen removal can provide a transient protection to the ischemic brain but has no beneficial effects on long-term protection. Taken together, these results strongly suggest that spleen removal cannot provide protection to the ischemic brain in the long run. In consistent with our conclusion, a recent study observed the lack of effect of splenectomy on long-term sensory motor functions after stroke [26].

 

Source:

http://doi.org/10.14336/AD.2018.0130

 

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