Tabriz University of Medical Sciences Journal of Research in Clinical Medicine 2717-0616 8 1 2020 02 15 Destructive effect of digitalis overdose on blood-brain barrier in rats; an experimental study 25 25 10.34172/jrcm.2020.025 EN Mehmet Nuri Kocak https://orcid.org/0000-0003-0828-520X Ozgur Caglar https://orcid.org/0000-0003-4000-4308 Dilek Destegul Kemal Alp Nalci Sevilay Ozmen Mehmet Dumlu Aydin Journal Article 10.34172/jrcm.2020.025 2020 05 01 2020 06 07 Introduction: Cardiac glycosides are widely used in critical cardiac diseases despite their unexplained mechanisms on cardio-respiratory system and other autonomic complications within both intra-uterine and post-natal life. The aim of this study is to investigate if digitalis overdose could cause a result in such complications by a destructive effect on blood-brain barrier (BBB). Methods: Twenty-five male Sprague Dawley rats weighing 300–350 g were divided into the following groups: control (n=5), sham (isotonic) (n=5), therapeutic dose (n=5), arrhythmogenic dose (n=5), and lethal dose (n=5). The animals were euthanized and their brains were extracted. The brains were histopathologically and immunohistochemically examined to evaluate BBB morphology in the superior temporal cortex. Results: One animal died because of experimental procedures on the first day. Macroscopic examination of brains revealed brain edema, subarachnoid hemorrhage (SAH), and narrowed cisterns in toxic doses of digitalis-treated animals. Brain histopathological examination of these groups revealed bloody subarachnoid and cisternal spaces, cortical arteriolar vasospasm, neurodegeneration, and even peri-arteriolar neuroglial component fragmentation; these changes induced BBB destruction in the high-dose digitalis-treated animals. Conclusion: Digitalis should not be used with overdoses if the cardio-respiratory arrhythmia is unexpectedly appearing in low doses against the possibility of defected or disrupted BBB.