Inhibition of astrocytic activity alleviates sequela in acute stages of intracerebral hemorrhage

// Cheng-Di Chiu 1, 3, 4, 5 , Nai-Wei Yao 1, 2, 5 , Jeng-Hung Guo 4 , Chiung-Chyi Shen 6 , Hsu-Tung Lee 7 , You-Pen Chiu 1, 5 , Hui-Ru Ji 3, 5 , Xianxiu Chen 1, 4, 5 , Chun-Chung Chen 1, 4, 5 and Chen Chang 2 1 School of Medicine, China Medical University, Taichung, Taiwan 2 Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan 3 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan 4 Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan 5 Stroke Center, China Medical University Hospital, Taichung, Taiwan 6 Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan 7 Department of Neurosurgical Oncology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan Correspondence to: Cheng-Di Chiu, email: cdchiu4046@gmail.com Keywords: acute stroke; intracerebral hemorrhage; astrocyte; blood–brain barrier; MRI Received: August 02, 2017     Accepted: September 22, 2017     Published: October 24, 2017 ABSTRACT Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group ( n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood–brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.