Dr. Zhong Chen/'s group published in Nature Communications

Recently, a research group headed by Prof. Chen Zhong at Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology, College of pharmaceutical sciences, Zhejiang University has published a research paper titled “Histamine H3 receptors aggravate cerebral ischemic injury by histamine-independent mechanisms” in Nature Communications. The investigation reported that H3R aggravates ischemic brain injury by histamine-independent mechanisms, and its antagonism may provide a novel neuroprotective strategy against cerebral ischemia by regulating autophagy.

Ischemic stroke is one of the leading causes of death worldwide. Unfortunately, few therapy has been demonstrated effective in the treatment of ischemic stroke.It has been proposed that H3R blockade is generally neuroprotective. However, its role in ischemia and the underlying mechanisms remains to be untangled. Prof. Chen’s group for the first time found that H3R antagonism and H3R deletion protected against I/R injury in a histamine-independent manner. H3R antagonism reinforced I/R-induced autophagy and the neuroprotection of H3R antagonism is reversed by autophagy blockade. Further investigations show that H3R antagonism inhibits the binding of H3R to chloride intracellular channel 4 (CLIC4), and subsequently further activates I/R-induced autophagy, which protects against ischemia injury. The present study provides new prospects for H3R antagonists in therapeutic intervention for cerebral ischemia.

Co-first authors of this article are Dr. Haijing Yan, Dr. Xiangnan Zhang and Dr. Weiwei Hu. This study was supported by National Basic Research of China 973 Program, the National Natural Science Foundation of China and the Program for the Zhejiang Leading Team of S&T Innovation.