PMID- 31220552 OWN - NLM STAT- MEDLINE DCOM- 20200724 LR - 20200724 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 150 DP - 2019 Aug TI - Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats. PG - 281-289 LID - S0361-9230(19)30129-7 [pii] LID - 10.1016/j.brainresbull.2019.06.010 [doi] AB - BACKGROUND: Vasogenic brain edema is the most important complication of ischemic stroke that aggravates primary brain injury. Ischemia-Reperfusion (IR)-induced Blood-Brain Barrier (BBB) impairment limits the use of recombinant tissue plasminogen activator (r-tPA) by increasing the possibility of hemorrhagic transformation and contributing to vasogenic edema and neuroinflammation. This study examined the effects of post-ischemic treatment with calcitriol on cerebral infarction, vasogenic edema formation and BBB disruption in a rat model of ischemic stroke. METHODS: Male Sprague-Dawley rats were divided into three main groups, including the sham, IR + vehicle and IR + calcitriol groups. Transient focal cerebral ischemia was induced by a 60-min-long occlusion of the left middle cerebral artery. The infarct volume, brain edema, BBB permeability and antioxidant enzyme activities were evaluated 24 h after ischemia. Immunohistochemical analysis was conducted to investigate cell apoptosis and Brain-Derived Neurotrophic Factor (BDNF) protein expression five days after ischemia. RESULTS: Compared to the IR + vehicle group, the IR + calcitriol group showed a reduced brain infarction volume, attenuated brain edema formation and improved BBB function. These protective effects were followed by the upregulation of antioxidant enzyme activities in the brain tissue. Additionally, a diminished cell apoptosis and an increased BDNF immunoreactivity were obtained in the IR + calcitriol group. CONCLUSION: Calcitriol may reduce brain injury and attenuate vasogenic edema by upregulating antioxidant enzymes activities, reducing cell apoptosis and increasing BDNF protein in the brain tissue in a rat model of ischemic stroke. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Sadeghian, Nooshin AU - Sadeghian N AD - Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. FAU - Shadman, Javad AU - Shadman J AD - Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. FAU - Moradi, Alireza AU - Moradi A AD - Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. FAU - Ghasem Golmohammadi, Mohammad AU - Ghasem Golmohammadi M AD - Department of Anatomy, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran. FAU - Panahpour, Hamdollah AU - Panahpour H AD - Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran; Physiological Studies Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: panahpour.h@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190618 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Antioxidants) RN - EC 3.4.21.68 (Tissue Plasminogen Activator) RN - FXC9231JVH (Calcitriol) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - Blood-Brain Barrier/*drug effects MH - Brain/metabolism MH - Brain Edema/*drug therapy MH - Brain Ischemia/metabolism MH - Calcitriol/metabolism/*pharmacology MH - Disease Models, Animal MH - Infarction, Middle Cerebral Artery/complications MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Stroke/metabolism MH - Tissue Plasminogen Activator/pharmacology OTO - NOTNLM OT - Antioxidant enzymes OT - Apoptosis OT - BDNF OT - Brain edema OT - Calcitriol OT - Stroke EDAT- 2019/06/21 06:00 MHDA- 2020/07/25 06:00 CRDT- 2019/06/21 06:00 PHST- 2019/02/12 00:00 [received] PHST- 2019/06/11 00:00 [revised] PHST- 2019/06/12 00:00 [accepted] PHST- 2019/06/21 06:00 [pubmed] PHST- 2020/07/25 06:00 [medline] PHST- 2019/06/21 06:00 [entrez] AID - S0361-9230(19)30129-7 [pii] AID - 10.1016/j.brainresbull.2019.06.010 [doi] PST - ppublish SO - Brain Res Bull. 2019 Aug;150:281-289. doi: 10.1016/j.brainresbull.2019.06.010. Epub 2019 Jun 18.