https://orcid.org/0000-0002-2852-8486
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ABSTRACT
Objective: Trans-resveratrol has been shown to have neuroprotective effects and could be a promising therapeutic agent in the treatment of intracerebral haemorrhage (ICH). This study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in trans-resveratrol-induced neuroprotection in rats with collagenase-induced ICH.
Methods: Sixty male Sprague–Dawley rats weighing 330–380 g were randomly divided into five groups (n = 12): (i) control, (ii) sham-operated rats, (iii) ICH rats pretreated with vehicle (0.1% DMSO saline, i.c.v.), (iv) ICH rats pretreated with trans-resveratrol (0.9 µg, i.c.v.) and (v) ICH rats pretreated with trans-resveratrol (0.9 µg) and the A1R antagonist, DPCPX (2.5 µg, i.c.v.). Thirty minutes after pretreatment, ICH was induced by intrastriatal injection of collagenase (0.04 U). Forty-eight hours after ICH, the rats were assessed using a variety of neurobehavioural tests. Subsequently, rats were sacrificed and brains were subjected to gross morphological examination of the haematoma area and histological examination of the damaged area.
Results: Severe neurobehavioural deficits and haematoma with diffuse oedema were observed after intrastriatal collagenase injection. Pretreatment with trans-resveratrol partially restored general locomotor activity, muscle strength and coordination, which was accompanied with reduction of haematoma volume by 73.22% (P < 0.05) and damaged area by 60.77% (P < 0.05) in comparison to the vehicle-pretreated ICH group. The trans-resveratrol-induced improvement in neurobehavioural outcomes and morphological features of brain tissues was inhibited by DPCPX pretreatment.
Conclusion: This study demonstrates that the A1R activation is possibly the mechanism underlying the trans-resveratrol-induced neurological and neurobehavioural protection in rats with ICH.
Acknowledgments
We acknowledge the administrative and facility support by Research Management Institute, Institute of Medical Molecular Biotechnology (IMMB), Laboratory Animal Care Unit, Anatomy Department and Centre for Neuroscience Research, Universiti Teknologi MARA, Malaysia.
Disclosure statement
No potential conflict of interest was reported by the authors.
Ethical approval
All procedures performed in this study involving animals were in accordance with the ethical standards of Committee on Animal Research and Ethics, Universiti Teknologi MARA Malaysia at which the present study was conducted. The ethics approval number is UiTM CARE: 241/2/2018 (6/4/2018).
Additional information
Funding
Notes on contributors
Noor Azliza Wani Abd. Aziz
Noor Azliza Wani Abd. Aziz is currently a postgraduate student at the Centre for Neuroscience (NeuRon), Faculty of Medicine (UiTM). She received her BSc Biomed. from Universiti Kebangsaan Malaysia (UKM) in 2003, MSc Biomed. from Universiti Islam Antarabangsa Malaysia in 2008 and MMedSc Anat from UKM in 2013. She has been a lecturer of Anatomy at Faculty of Dentistry (UiTM) from 2013 and is currently pursuing her PhD. Her research interest includes adenosine A1 receptor-mediated neuroprotection in stroke and new neuroprotective strategies for intracerebral haemorrhage.
Igor Iezhitsa
Dr. Igor Iezhitsa has been in the field of pharmacology more than 20 years. Since the beginning of his professional career, he has been deeply involved in academic and research activities. He received his PhD in Pharmacology from Volgograd State Medical University (Russia) in 1998 and degree of the Doctor of Biological Science (Dr. Sci. Biol.) in Pharmacology from above-mentioned University in 2008. He played a pivotal role in the preclinical study of new group of CNS stimulants in the Volgograd State Medical University (Russia) in 1994-2000, and has since been involved in screening and preclinical study of many new pharmacological compounds. In June 2009, he joined Faculty of Medicine of the Universiti Teknologi MARA (UiTM), Malaysia as Associate Professor of Pharmacology. Since 2013 he was involved in setting up Centre for Neuroscience (NeuRon) at Faculty of Medicine (UiTM) and from 2015 he served as a head of above mentioned Centre. His research interests include experimental neuropharmacology and toxicology, neuroprotection, and ocular pharmacology. Dr. Igor has published more than 60 articles in indexed journals and has authored 5 books and chapters. He has supervised 6 PhD and 4 Master degree students. He has presented in numerous national and international conferences and has been an invited speaker on many occasions.
Renu Agarwal
Dr Renu Agarwal is a pharmacologist and is actively involved in academics and research for almost 20 years. She obtained PhD in Pharmacology from University of Delhi, India, and is currently working as Professor of Pharmacology at the School of Medicine, International Medical University, Malaysia. She has been actively involved in undergraduate and postgraduate teaching of medical and pharmacy students for several years. Ocular pharmacology and neurotherapeutics is her special research interest. Her experimental work in glaucoma, cataract, uveitis and diabetic retinopathy is widely published in national and international journals and books of high repute.
Roqiah Fatmawati Abdul Kadir
Dr Roqiah Fatmawati Abdul Kadir graduated from National University of Ireland in Galway, Ireland in year 2007 and had completed her internship in Ireland. She graduated with a master's degree in University of Malaya in 2017. She is currently a medical lecturer at Faculty of Medicine, Universiti Teknologi MARA (UiTM), Malaysia and has strong academic interest in pre-clinical stroke research.
Azian Abd. Latiff
Dr Azian Abd. Latiff graduated with a medical degree from Universitas Indonesia in 1981, Master in Medical Science (Anatomy) and a PhD from Universiti Kebangsaan Malaysia in 1991 and 2003 respectively. She has been involved in teaching Anatomy in Universiti Kebangsaan Malaysia (UKM) since 1985 and has taught both undergraduate and postgraduate students. She has been an External Examiner in Anatomy in both local and international universities. Her research interests include effects of natural products on basic tissues including nerve cells, anatomy medical education and issues on quality assurance. She has published more than 50 papers and presented the research findings in various conferences. She has been involved in quality assurance activities since the year 2000 and has held various administrative positions related to quality assurance namely Head of Quality Department, UKM Medical Centre (2008-2011) dealing with both academic and hospital services. After her retirement from UKM, she joined Universiti Teknologi MARA (UiTM) and served as the Deputy Dean for Postgraduate and Professional Training in UiTM from 2014 till 2018. She has supervised 4 PhD and 10 master students in Anatomy
Nafeeza Mohd Ismail
Dr Nafeeza Mohd Ismail is currently Professor and Dean, School of Medicine at International Medical University (IMU), Malaysia. She has more than 30 years of professional experience in this field. She was also the President and Executive Member of the Malaysian Society of Pharmacology and Physiology (MSPP); Malaysian Scientific Association; Malaysian Islamic Medical Society; and University Malaya Medical Alumni. Prior to joining IMU, Prof Nafeeza was the Dean, Faculty of Medicine, Universiti Teknologi MARA (UiTM). She also played key roles in the UiTM Private Healthcare where she was the Chair as well as a Board Member for the Organization. Her research interests are in the areas of metabolism in chronic diseases, antioxidants in various fields including atherosclerosis, peptic ulcer disease, eye diseases and neuroscience.