Displaying all 10 publications

Abstract:
Sort:
  1. Singh D, Narayanan S, Vicknasingam B
    Brain Res Bull, 2016 09;126(Pt 1):41-46.
    PMID: 27178014 DOI: 10.1016/j.brainresbull.2016.05.004
    INTRODUCTION: The objective of the paper was to highlight the differences in the traditional and non-traditional users of kratom in the South East Asian and Western contexts.

    METHOD: A literature survey of published kratom studies among humans was conducted. Forty published studies relevant to the objective were reviewed.

    RESULTS: Apart from the differences in the sources of supply, patterns of use and social acceptability of kratom within these two regions, the most interesting finding is its evolution to a recreational drug in both settings and the severity of the adverse effects of kratom use reported in the West. While several cases of toxicity and death have emerged in the West, such reports have been non-existent in South East Asia where kratom has had a longer history of use. We highlight the possible reasons for this as discussed in the literature. More importantly, it should be borne in mind that the individual clinical case-reports emerging from the West that link kratom use to adverse reactions or fatalities frequently pertained to kratom used together with other substances. Therefore, there is a danger of these reports being used to strengthen the case for legal sanction against kratom. This would be unfortunate since the experiences from South East Asia suggest considerable potential for therapeutic use among people who use drugs.

    CONCLUSION: Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.

  2. Suhaimi FW, Yusoff NH, Hassan R, Mansor SM, Navaratnam V, Müller CP, et al.
    Brain Res Bull, 2016 09;126(Pt 1):29-40.
    PMID: 27018165 DOI: 10.1016/j.brainresbull.2016.03.015
    Kratom or its main alkaloid, mitragynine is derived from the plant Mitragyna speciosa Korth which is indigenous to Southeast Asian countries. This substance has become widely available in other countries like Europe and United States due to its opium- and coca-like effects. In this article, we have reviewed available reports on mitragynine and other M. speciosa extracts. M. speciosa has been proven to have a rewarding effect and is effective in alleviating the morphine and ethanol withdrawal effects. However, studies in human revealed that prolonged consumption of this plant led to dependence and tolerance while cessation caused a series of aversive withdrawal symptoms. Findings also showed that M. speciosa extracts possess antinociceptive, anti-inflammatory, anti-depressant, and muscle relaxant properties. Available evidence further supports the adverse effects of M. speciosa preparations, mitragynine on cognition. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca2+ channels, expression of cAMP and CREB protein and via descending monoaminergic system. Physicochemical properties of mitragynine have been documented which may further explain the variation in pharmacological responses. In summary, current researchs on its main indole alkaloid, mitragynine suggest both therapeutic and addictive potential but further research on its molecular effects is needed.
  3. Sekaran H, Gan CY, A Latiff A, Harvey TM, Mohd Nazri L, Hanapi NA, et al.
    Brain Res Bull, 2019 10;152:63-73.
    PMID: 31301381 DOI: 10.1016/j.brainresbull.2019.07.010
    Cerebral hypoperfusion involved a reduction in cerebral blood flow, leading to neuronal dysfunction, microglial activation and white matter degeneration. The effects on the blood-brain barrier (BBB) however, have not been well-documented. Here, two-vessel occlusion model was adopted to mimic the condition of cerebral hypoperfusion in Sprague-Dawley rats. The BBB permeability to high and low molecular weight exogenous tracers i.e. Evans blue dye and sodium fluorescein respectively, showed marked extravasation of the Evans blue dye in the frontal cortex, posterior cortex and thalamus-midbrain at day 1 following induction of cerebral hypoperfusion. Transmission electron microscopy revealed brain endothelial cell and astrocyte damages including increased pinocytotic vesicles and formation of membrane invaginations in the endothelial cells, and swelling of the astrocytes' end-feet. Investigation on brain microvessel protein expressions using two-dimensional (2D) gel electrophoresis coupled with LC-MS/MS showed that proteins involved in mitochondrial energy metabolism, transcription regulation, cytoskeleton maintenance and signaling pathways were differently expressed. The expression of aconitate hydratase, heterogeneous nuclear ribonucleoprotein, enoyl Co-A hydratase and beta-synuclein were downregulated, while the opposite observed for calreticulin and enhancer of rudimentary homolog. These findings provide insights into the BBB molecular responses to cerebral hypoperfusion, which may assist development of future therapeutic strategies.
  4. Najafi R, Hosseini A, Ghaznavi H, Mehrzadi S, Sharifi AM
    Brain Res Bull, 2017 May;131:117-122.
    PMID: 28373151 DOI: 10.1016/j.brainresbull.2017.03.013
    OBJECTIVE: Neuropathies are a nerve disorders that caused by diabetes. Neuropathy affects over 50% of diabetic patients. High blood glucose and their toxic byproducts are the main causes for nerve dysfunction. In the present study, we examined the neroprotective effects of cerium oxide (CeO2) nanoparticles in diabetic rats.

    METHOD: Rats divided into four groups: control group, diabetic group, the diabetic group treated with CeO2nanoparticle at a dose of 65mg/kg and diabetic group received CeO2nanoparticle at a dose of 85mg/kg. Diabetes was induced by single intraperitoneal injection of 65mg/kg streptozotocin (STZ). 8 weeks after the induction of diabetes, body weight and pain sensitivity in all groups were measured. The blood sample was collected for biochemical analysis. The dorsal root ganglion (DRG) neurons were isolated for histopathological stain and morphometric parameters studies.

    RESULTS: Reduction of body weight, total thiol molecules (TTM), total antioxidant power (TAP) and ADP/ATP ratio in diabetic rat was reversed by CeO2nanoparticles administration. We showed that lipid peroxidation (LPO) and nociception latency were significantly increased in STZ-treated rats and decreased after CeO2nanoparticles administration. DRG neurons showed obvious vacuole and various changes in diameter, area and the count of A and B cells in STZ-diabetic rat. CeO2nanoparticles improved the histopathology and morphological abnormalities of DRG neurons.

    CONCLUSION: Our study concluded the CeO2nanoparticles have a protective effect against the development of DN.

  5. Venugopal C, Shobha K, Rai KS, Dhanushkodi A
    Brain Res Bull, 2022 Mar;180:46-58.
    PMID: 34979238 DOI: 10.1016/j.brainresbull.2021.12.012
    Progressive hippocampal neuronal losses, neuroinflammation, declined neurogenesis and impaired hippocampal functions are pathological features of Alzheimer's disease and temporal lobe epilepsy (TLE). Halting neuroinflammation and progressive neurodegeneration in the hippocampus is a major challenge in treating such disease conditions which, if unsuccessful would lead to learning/memory dysfunction and co-morbidities like anxiety/depression. Mesenchymal stem cells (MSCs) therapy provides hope for treating neurodegenerative diseases by either replacing lost neurons by transplantation of MSCs which might differentiate into appropriate neuronal phenotypes or by stimulating the resident neural stem cells for proliferation/differentiation. In this current study, we demonstrate that the intrahippocampal transplantation of ectoderm originated dental pulp stem cells (DPSCs) or intrahippocampal injection of DPSCs condition medium (DPSCs-CM) in a mouse model of hippocampal neurodegeneration could efficiently prevent neurodegeneration, neuroinflammation, enhance hippocampal neurogenesis and spatial learning and memory functions much superior to commonly used bone marrow mesenchymal stem cells (BM-MSCs) or its secretome. Probing the possible mechanisms of neuroprotection revealed that DPSCs/DPSCs-CM treatment upregulated an array of hosts' endogenous neural survival factors expression, reduced pro-apoptotic caspase activity and upregulated the anti-apoptotic factors BCL-2 and phosphorylated PI3K prominently than BM-MSCs/BM-MSCs-CM, suggesting that among MSCs, neural crest originated DPSCs might be a better adult stem cell candidate for treating neurodegenerative diseases.
  6. Hassan R, Othman N, Mansor SM, Müller CP, Hassan Z
    Brain Res Bull, 2021 07;172:139-150.
    PMID: 33901587 DOI: 10.1016/j.brainresbull.2021.04.018
    Mitragyna speciosa, also known as kratom, has been used for mitigating the severity of opioid withdrawal in humans. Its main indole alkaloid, mitragynine, has been considered as a pharmacotherapy for pain conditions and opioid replacement therapy. However, at high doses, chronic mitragynine may also have an addiction potential. The effects of chronic action of mitragynine in the brain are still unknown. The present study developed a mitragynine withdrawal model in rats and used it for a proteomic analysis of mitragynine withdrawal effects. Mitragynine (30 mg/kg, i.p.) was administered daily over a period of 14 days and then withdrawn. A proteomic analysis revealed that from a total of 1524 proteins identified, 31 proteins were upregulated, and 3 proteins were downregulated in the mitragynine withdrawal model. The Rab35 protein expression increased most profoundly in the mitragynine withdrawal group as compared to vehicle group. Therefore, it is proposed that Rab35 in the brain might be considered as a potential biomarker during mitragynine withdrawal and might be valuable target protein in developing new pharmacotherapies in the future.
  7. Yusoff NHM, Hassan Z, Murugaiyah V, Müller CP
    Brain Res Bull, 2022 01;178:1-8.
    PMID: 34774992 DOI: 10.1016/j.brainresbull.2021.11.002
    Kratom, derived from the plant Mitragyna speciosa (M. speciosa) Korth is a traditional psychoactive preparation widely used in Southeast Asia and increasingly in the rest of the world. Use and abuse of Kratom preparations can be attributed to mitragynine (MIT), the main psychoactive compound isolated from its leaves. While MIT may have beneficial effects as a recreational drug, for pain management, and for opiate withdrawal, it may have an addiction potential at higher doses. However, its action in the reward system of the brain is currently unknown. This study investigated how mitragynine (10 mg/kg, i.p.) affects extracellular activity of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) of the brain, compared to morphine (MOR; 10 mg/kg, i.p.) and methamphetamine (METH; 10 mg/kg, i.p.). Using in-vivo microdialysis in freely moving rats, we found a significant increase of extracellular DA after MOR and METH, but not after MIT in all three brain regions. MIT led to a significant increase of DOPAC and/or HVA in these brain regions while MOR and METH had only moderate effects. These findings suggest a strong and prolonged effect of MIT on DA synthesis/metabolism, but not on extracellular DA activity, which may limit the addiction risk of MIT, in contrast to MOR and METH.
  8. Vijayanathan Y, Hamzah NM, Lim SM, Lim FT, Tan MP, Majeed ABA, et al.
    Brain Res Bull, 2022 Nov;190:218-233.
    PMID: 36228872 DOI: 10.1016/j.brainresbull.2022.10.001
    In order to understand the biological processes underlying dopaminergic neurons (DpN) regeneration in a 6-hydroxydopamine(6-OHDA)-induced adult zebrafish-based Parkinson's disease model, this study investigated the specific phases of neuroregeneration in a time-based manner. Bromodeoxyuridine (BrdU) was administered 24 h before the harvest of brain tissues at day three, five, seven, nine, 12 and 14 postlesion. Potential migration of proliferative cells was tracked over 14 days postlesion through double-pulse tracking [BrdU and 5-ethynyl-2'-deoxyuridine (EdU)] of cells and immunohistostaining of astrocytes [glial fibrillary acidic protein (GFAP)]. Gene expression of foxa2 and nurr1 (nr4a2a) at day three, nine, 14, 18, 22 and 30 postlesion was quantified using qPCR. Protein expression of foxa2 at day three, seven, 14 and 22 postlesion was validated using the western blot technique. Double labelling [EdU and tyrosine hydroxylase (TH)] of proliferative cells was performed to ascertain their fate after the neuroregeneration processes. It was found that whilst cell proliferation remained unchanged in the area of substantial DpN loss, the ventral diencephalon (vDn), there was a transient increase of cell proliferation in the olfactory bulb (OB) and telencephalon (Tel) seven days postlesion. BrdU-immunoreactive (ir)/ EdU-ir cells and activated astrocytes were later found to be significantly increased in the vDn and its nearby area (Tel) 14 days postlesion. There was a significant but transient downregulation of foxa2 at day three and nine postlesion, and nr4a2a at day three, nine and 14 postlesion. The expression of both genes remained unchanged in the OB and Tel. There was a transient downregulation of foxa2 protein expression at day three and seven postlesion. The significant increase of EdU-ir/ TH-ir cells in the vDn 30 days postlesion indicates maturation of proliferative cells (formed between day five-seven postlesion) into DpN. The present findings warrant future investigation of critical factors that govern the distinctive phases of DpN regeneration.
  9. Tong T, Hao C, Shen J, Liu S, Yan S, Aslam MS, et al.
    Brain Res Bull, 2024 Jan;206:110838.
    PMID: 38123022 DOI: 10.1016/j.brainresbull.2023.110838
    BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus.

    METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg).

    RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal.

    CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links