Q&A with Dr. Liu
Stroke Progress and Innovation Awards 2016
Xiangrong Liu, MD, PhD
Xiangrong Liu, Jia Liu, Shangfeng Zhao, Haiyue Zhang, Wei Cai, Mengfei Cai, Xunming Ji, Rehana K. Leak, Yanqin Gao, Jun Chen, Xiaoming Hu
SPOTLIGHT: Q&A with Dr. Liu
What is the key take-away message from your article?
IL-4 is an important immune modulator serving to improve long-term outcomes after stroke by regulating microglia/macrophage responses and promoting an immune milieu that is highly permissive for behavioral recovery.
What prompted you and your co-authors to perform this study?
Activated microglia/macrophages of distinct phenotypes can critically determine the outcomes after brain injuries. We recently observed a predominant inflammatory (M1) microglial response with stroke progression, resulting in an unfavorable environment for brain recovery (Hu X et al. 2012 Stroke;43:3063-3070). Furthermore, aged mice exhibited fewer tissue-repairing (M2) microglia/macrophages shortly after stroke, and this was accompanied by exacerbation of long-term functional deficits (Suenaga J et al. 2015 Exp Neurol; 272, 109-119). Thus, molecules that promote beneficial microglial responses may help promote functional recovery after ischemic stroke. IL-4 is thus far the best characterized promoter of M2 polarization for microglia and macrophages; however, its role in microglia regulation in long-term stroke outcomes was not previously known.
What is innovative about this work? And what are its applications?
There are no restorative therapies available to promote long-term recovery after ischemic stroke, partly due to the traditionally neurocentric view of the central nervous system. Furthermore, microglial polarization into distinct phenotypes has only recently emerged as an important determinant of stroke outcomes because glial biology is less well understood than neuron biology. Our study is the first to investigate the potential for IL-4 to foster long-term recovery after stroke through the modulation of microglial responses. The results strongly support IL-4 as a therapeutic target for stroke. In addition, the therapeutic use of IL-4 may translate to other pathophysiological conditions, such as traumatic brain injury.
Tell us about the biggest challenge you came across while conducting this study.
As mentioned above, previous stroke research emphasizes neuronal protection, whereas much less progress has been made about non-neuronal cells. We found that IL-4 could enhance long-term recovery after stroke without reducing neuronal tissue loss. For the completion of our study, we had to optimize measurements that are technically demanding, such as the long-term behavior tests to evaluate the functional recovery after stroke.
Is there anything more you would like to add about your work?
In the past few decades, many neuroprotective drugs have shown promise in preclinical testing but failed in the clinic. One major concern is that preclinical studies focus almost exclusively on protection of neurons in gray matter, whereas the effects of therapies on non-neuronal tissues are largely unexplored. Furthermore, the close relationship between the immune balance and brain recovery is only beginning to be elucidated. Our study rectifies these gaps by focusing on an immune mechanism that enhances functional recovery after stroke. We hope that we have opened up a new path for more research on immunomodulators and therapies that target non-neuronal cells.
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