Neuroprotection by trans-resveratrol against collagenase-induced neurological and neurobehavioural deficits in rats involves adenosine A1 receptors |
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Authors: | Noor Azliza Wani Abd. Aziz Renu Agarwal Roqiah Fatmawati Abdul Kadir Azian Abd. Latiff Nafeeza Mohd Ismail |
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Affiliation: | 1. Centre for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia;2. Centre of PreClinical Science Studies, Faculty of Dentistry, Universiti Teknologi MARA, Sungai Buloh, Malaysia;3. School of Medicine, International Medical University, Kuala Lumpur, Malaysiahttps://orcid.org/0000-0002-3050-7449;4. Department of Radiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysiahttps://orcid.org/0000-0002-2772-8283;5. Department of Anatomy, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia;6. School of Medicine, International Medical University, Kuala Lumpur, Malaysia |
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Abstract: | ABSTRACTObjective: 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. |
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Keywords: | Intracerebral haemorrhage neuroprotection trans-resveratrol adenosine A1 receptor 1-dipropyl-8-cyclopentylxanthine (DPCPX) neurological and neurobehavioural deficits |
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