| Background and PurposeStroke is the most common neurological diseases, and is a general term for diseasescaused by a variety of cerebrovascular reasons. The majority (over80%) of stroke isischemic stroke. Due to the failure to early diagnosis and effective treatment,10%ofischemic stroke patients had died. And, more than50%of patients had left permanentdisability. Ischemic stroke are a heavy burden to the patients themselves, their familyand society.Treatment of acute cerebral infarction is still challenging. Therefore, we need tofind new treatments. In order to looking for new treatments, we need to do morein-depth researches about the pathophysiological mechanisms on cerebral infarction.However, the pathophysiological mechanisms of cerebral infarction are verycomplicated, which include the following: acidosis, intracellular calcium overload,excitatory amino acids (EAAs) exitotoxicity, the damage of inflammatory cytokines,and so on. Now, immunomodulatory therapy has been proofed effective in animalexperiments, which may be a breakthrough in the treatment of cerebral infarction.As a major peripheral immune organ, spleen plays a key role in the stroke-inducedimmune response. Study found that spleen shrunk significantly and the function of the spleen changed after cerebral infarction. Some scholars believe that the spleen may bea potential target for the treatment of cerebral infarction. At present, research on therelationship between the spleen and cerebral infarction is few abroad and rare at home.Therefore, it is necessary to conduct deeper study on the relationship between thespleen and cerebral infarction.In this study, we use the intraluminal suture method to build middle cerebral arteryocclusion (MCAO) model in rats, and investigate the effect of splenectomy andprobable mechanisms on that rat models.Methods(1) Animals and grouping: Thirty six male SD rats were randomly divided into3groups: MCAO control group, sham splenectomy group, splenectomy group (n=12in each group).(2) Splenectomy model: According to abdominal operation practice, abdominalwall was incised. The blood vessels were tied off and ligated. With blunt forceps, thespleen was exteriorized through the incision. The abdominal wall and incision wereclosed with sutures after stanching. Sham-operated rats were treated identically withthe exception of removal of the spleen.(3) MCAO model: Focal ischemia was achieved during MCAO by using theintraluminal suture technique.(4) The infarct volume was measured with Nissl Body staining.(5) The number of T cells, neutrophils, and macrophages in ischemic regions weredetected with immunofluorescence staining.(6) The productions of IL-1β, TNF-α, and IL-10in the sera and ischemic brainhomogenates were measured with the appropriate ELISA kits.Results(1) The infarct volume in the splenectomy group (34.93%±3.23%) wassignificantly small than that in the sham splenectomy group (74.33%±2.36%，P <0.001) and the control group (77.30%±2.62%，P <0.001).(2) The number of T cells of the ischemic regions in the control group (52.15± 10.85/mm~2，p <0.001) and sham splenectomy group (46.46±13.44/mm~2，p <0.001)was significantly more than that in the splenectomy group (17.44±7.33/mm~2).(3) The number of neutrophils of the ischemic regions in the control group (56.46±11.25/mm~2，p=0.001) and sham splenectomy group (47.56±9.04/mm~2，p=0.032)was significantly more than that in the splenectomy group (35.56±4.83/mm~2).(4) The number of macrophages of the ischemic regions in the control group (39.31±8.69/mm~2，p <0.001) and sham splenectomy group (43.13±9.10/mm~2，p <0.001)was significantly more than that in the splenectomy group (7.08±2.23/mm~2).(5) The inflammatory cytokines of ischemic brain homogenates: The level of IL-1βin the control group (23.06±7.01pg/mg，p=0.04) and sham splenectomy group(24.04±4.81pg/mg，p=0.02) was higher than that in the splenectomy group (16.63±1.09pg/mg). The level of TNF-α in the control group (2.20±0.29pg/mg，p=0.01)and sham splenectomy group (2.09±0.39pg/mg，p=0.034) was higher than that inthe splenectomy group (1.71±0.10pg/mg). On the contrary, the level of IL-10in thesplenectomy group (1.14±0.28pg/mg) was significantly higher than that in the shamsplenectomy group (0.58±0.09pg/mg，p <0.001) and the control group (0.67±0.22pg/mg，p=0.002).(6) Serum inflammatory cytokines: The difference in the level of IL-1β and TNF-αwas consistent with the results in brain homogenates. However, there was nosignificant difference in the level of IL-10among these three groups.Conclusions(1) Splenectomy can reduce the infarct volume in the rat model of MCAO.(2) The effect of splenectomy may be related to the decrease of inflammatory cells(T cells, neutrophils, macrophages).(3) The effect of splenectomy may be related to the reduction of pro-inflammatorycytokines (IL-1β and TNF-α).(4) The effect of splenectomy may be related to the increase of anti-inflammatorycytokine (IL-10). |
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