Description
Splenectomy fails to provide long-term protection against ischemic stroke
Yuanyuan Ran1, Zongjian Liu1, Shuo Huang1, Xiaoming Hu1,2
1Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing 101100, China; 2Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
Correspondence: Dr. Xiaoming Hu, Department of Neurology, University of Pittsburgh School of Medicine, 200 Lothrop Street, SBST 506, Pittsburgh, PA 15213, USA
Tel: 412-648-8991, Fax: 412-383-9985, e-mail: hux2@upmc.edu
or
Dr. Zongjian Liu, Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Xinhua South Road 82, Tongzhou District, Beijing, China, Tel.: +86-10-69543901, Fax: +1-4126924636,
E-mail: liuzj7606@126.com
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 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 showed 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.
Keywords: cerebral ischemia; splenectomy; lymphocytes; neurological function