The protective effects of T cell deficiency against brain injury are ischemic model-dependent in rats

Abstract

Previous studies have reported that T cell deficiency reduced infarct sizes after transient middle cerebral artery (MCA) suture occlusion in mice. However, how reperfusion and different models affect the detrimental effects of T cells have not been studied. We investigated the effects of T cell deficiency in nude rats using two stroke models and compared their infarct sizes with those in WT rats. In the distal MCA occlusion (MCAo) model, the distal MCA was permanently occluded and the bilateral common carotid arteries (CCAs) were transiently occluded for 60 min. In the suture MCAo model, the MCA was transiently occluded for 100 min by the insertion of a monofilament suture. Our results showed that T cell deficiency resulted in about a 50% reduction in infarct size in the suture MCAo model, whereas it had no effect in the distal MCAo model, suggesting the protective effects of T cell deficiency are dependent on the ischemic model used. We further found more total T cells, CD4 T cells and CD8 T cells in the ischemic brains of WT rats in the suture MCAo model than in the distal MCAo model. In addition, we detected more CD68-expressing macrophages in the ischemic brains of WT rats than in nude rats in the suture MCAo but not the distal MCAo model. Lymphocyte reconstitution in nude rats resulted in larger infarct sizes in the suture MCAo, but not in the distal MCAo stroke model. The results of regional CBF measurement indicated a total reperfusion in the MCAo model but only a partial reperfusion in the distal MCAo model. In conclusion, the protective effects of T cell deficiency on brain injury are dependent on the ischemic model used; likely associated with different degrees of reperfusion.

Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

“…There are a series of experiments that show the harmful role of T lymphocytes, among which are those performed by Gokhan [26] and his team in 2006 where they observed that lymphocytes are the primary producers of INF-and other proinlammatory cytokines, that promotes an increment in infarct size [26] and those performed by Liesz in 2011 [63], in which they observed that by eliminating lymphocytes, infarct size was reduced in animals subjected to cerebral ischemia, all of which matches with Xiong et al's results in 2013 [64], where they observed that T lymphocyte deiciency signiicantly reduces infarct volume in a transient cerebral ischemia model, but not in distal permanent occlusion, which highlights that the model and level of reperfusion used are essential and diferential to evaluate damage.…”

“…Natural killer NK cells have a less noxious efect. T cells show an injurious efect at the experimental level through the production of IL-1 , IL-23 [38,63,64] and IL-6 at the clinical level [6 ]. Treg lymphocytes have been implicated mostly in neural tissue protection, preventing autoimmunity and inlammation through IL-10 [66].…”

T Cells and Cerebral Ischemic Stroke

“…T cells in the ischemic brains than dMCAO. We believed that the reason caused above phenomena were mainly associated with different degrees of reperfusion [35].…”

The Use of microRNAs to Modulate Redox and Immune Response to Stroke

“…The absence of T cells has been shown by several groups to reduce ischemic injury, although the extent of reperfusion may be important to this effect (193). Paradoxically, poststroke immune suppression is known to render stroke patients vulnerable to infections, including pneumonia and sepsis, acting, in part, by activation of the a7 nicotinic acetylcholine receptor to inhibit neutrophil and macrophage accumulation and function (91).…”