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  1. Glutamate receptors and transporters as comparative cues to the glutamatergic circuits of the avian and mammalian brain
    Islam, M.R., Muzaimi, M., Abdullah, J.M.
    Orient Neuron Nexus, 2011;2(1):2-9.
    MyJurnal
    Glutamate is the principal excitatory neurotransmitter in the central nervous system, and plays important roles in both physiological and pathological neuronal processes. Current understanding of the exact mechanisms involved in glutamate-induced neuronal excitotoxicity, in which excessive glutamate causes neuronal dysfunction and degeneration, whether acute or chronic, remain elusive. Conditions, due to acute insults such as ischaemia and traumatic brain injury, and chronic neurodegenerative disorders such as multiple sclerosis and motor neuron disease, suffer from the lack of translational neuroprotection in clinical setting to tackle glutamate excitotoxicity despite steady growth of animal studies that revealed complex cell death pathway interactions. In addition, glutamates are also released by non-neuronal cells including astrocytes and oligodendroglia. Thus, attempts to elucidate this complexity are closely related to our understanding of the glutamatergic circuitry in the brain. Neuronal cells develop a glutamatergic system at glutamatergic synapses that utilise glutamate as an intercellular signaling molecule to characterise the output, input, and termination of this signaling. As to signal input, various kinds of glutamate receptors have been identified and characterized. Na+-dependent glutamate transporters at the plasma membrane are responsible for the signal termination through sequestration of glutamate from the synaptic cleft. The signal output systems comprise vesicular storage and subsequent exocytosis of glutamate by using vesicular glutamate transporters. Similar to the mammalian brain, the regional differences of glutamatergic neurons and glutamate receptor neurons suggest many glutamatergic projections in the avian brain, as supported by recent evidence of glutamate-related genes distribution. Glutamatergic target areas are expected to show high activity of glutamate transporters that remove released glutamate from the synaptic clefts. This review summarises and compares glutamatergic circuits in the avian and mammalian brain, particularly in the olfactory pathway, the paffial organization of glutamatergic neurons and connection with the striatum, hippocampal-septal pathway, visual and auditory pathways, and granule cell-Purkinje cell pathway in the cerebellum. Comparative appreciation of these glutamatergic circuits, particularly with the localisation and/or expression of specific subtypes of glutamate transporters, would provide the morphological basis for physiological and pharmacological designs that supplement existing animal studies of the current proposed mechanisms that underlie glutamate-induced neuronal excitotoxicity.
  2. Fulltext Insights from the preliminary autocorrelation analysis of low frequency neuronal oscillations during Quran listening
    Reza, F., Begum, T., Ahmed, A.L., Omar, H., Muzaimi, M., Abdullah, J.M.
    ASM Science Journal, 2012;6(1):39-45.
    MyJurnal
    The human brain generates different oscillations at different frequencies during various consciousness levels. When these brain waves synchronize with exogenous rhythmic stimulation, the brain experiences strong, yet relaxing emotion that could be involved in the formation of memory. We investigated the character of rhythmic oscillatory dynamics by electroencephalography (EEG) of subjects listening to a short verse of the Holy Quran compared to resting and Arabic news listening. The mean power amplitudes of each frequency band for wavelet-based time-frequency analysis were obtained from 5000 ms of segmented EEG recordings during rest, news and Quran listening conditions. The time series analysis of power from each of three conditions in each frequency band from the grand averaged data was then subjected to autocorrelation study. The results showed significant cyclic overall trends of increasing and decreasing patterns of power in the low frequency brain wave oscillation of different head regions especially global, frontal and temporal sites. These results provided a basis for prediction of the periodicity of the power of the oscillatory brain dynamics of delta and robustly in theta regions which occurred during Quran listening. Despite several limitations, our data offered a plausible scientific basis to the emotional induction during Quran listening that mimics recognized as data from music listening studies. This offered a promising perspective for future studies in translational neurophysiological, cognitive and biofeedback on Quran listening to modify brain behaviour in health and disease.
  3. Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats
    Hazim AI, Ramanathan S, Parthasarathy S, Muzaimi M, Mansor SM
    J Physiol Sci, 2014 May;64(3):161-9.
    PMID: 24464759 DOI: 10.1007/s12576-014-0304-0
    The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.
  4. Effective Connectivity for Default Mode Network Analysis of Alcoholism
    Khan DM, Kamel N, Muzaimi M, Hill T
    Brain Connect, 2021 02;11(1):12-29.
    PMID: 32842756 DOI: 10.1089/brain.2019.0721
    Introduction: With the recent technical advances in brain imaging modalities such as magnetic resonance imaging, positron emission tomography, and functional magnetic resonance imaging (fMRI), researchers' interests have inclined over the years to study brain functions through the analysis of the variations in the statistical dependence among various brain regions. Through its wide use in studying brain connectivity, the low temporal resolution of the fMRI represented by the limited number of samples per second, in addition to its dependence on brain slow hemodynamic changes, makes it of limited capability in studying the fast underlying neural processes during information exchange between brain regions. Materials and Methods: In this article, the high temporal resolution of the electroencephalography (EEG) is utilized to estimate the effective connectivity within the default mode network (DMN). The EEG data are collected from 20 subjects with alcoholism and 25 healthy subjects (controls), and used to obtain the effective connectivity diagram of the DMN using the Partial Directed Coherence algorithm. Results: The resulting effective connectivity diagram within the DMN shows the unidirectional causal effect of each region on the other. The variations in the causal effects within the DMN between controls and alcoholics show clear correlation with the symptoms that are usually associated with alcoholism, such as cognitive and memory impairments, executive control, and attention deficiency. The correlation between the exchanged causal effects within the DMN and symptoms related to alcoholism is discussed and properly analyzed. Conclusion: The establishment of the causal differences between control and alcoholic subjects within the DMN regions provides valuable insight into the mechanism by which alcohol modulates our cognitive and executive functions and creates better possibility for effective treatment of alcohol use disorder.
  5. Editorial: New challenges and future perspectives in pathological conditions
    Muzaimi M, Prakash KNB, Cheah PS, Feng L
    Front Behav Neurosci, 2023;17:1201044.
    PMID: 37304763 DOI: 10.3389/fnbeh.2023.1201044
  6. Fulltext Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study
    Idris Z, Zenian MS, Muzaimi M, Hamid WZ
    Asian J Neurosurg, 2014 Jul-Sep;9(3):115-23.
    PMID: 25685201 DOI: 10.4103/1793-5482.142690
    Induced hypothermia for treatment of traumatic brain injury is controversial. Since many pathways involved in the pathophysiology of secondary brain injury are temperature dependent, regional brain hypothermia is thought capable to mitigate those processes. The objectives of this study are to assess the therapeutic effects and complications of regional brain cooling in severe head injury with Glasgow coma scale (GCS) 6-7.
  7. Time course of motor and cognitive functions after chronic cerebral ischemia in rats
    Damodaran T, Hassan Z, Navaratnam V, Muzaimi M, Ng G, Müller CP, et al.
    Behav Brain Res, 2014 Dec 15;275:252-8.
    PMID: 25239606 DOI: 10.1016/j.bbr.2014.09.014
    Cerebral ischemia is one of the leading causes of death and long-term disability in aging populations, due to the frequent occurrence of irreversible brain damage and subsequent loss of neuronal function which lead to cognitive impairment and some motor dysfunction. In the present study, the real time course of motor and cognitive functions were evaluated following the chronic cerebral ischemia induced by permanent, bilateral occlusion of the common carotid arteries (PBOCCA). Male Sprague Dawley rats (200-300g) were subjected to PBOCCA or sham-operated surgery and tested 1, 2, 3 and 4 weeks following the ischemic insult. The results showed that PBOCCA significantly reduced step-through latency in a passive avoidance task at all time points when compared to the sham-operated group. PBOCCA rats also showed significant increase in escape latencies during training in the Morris water maze, as well as a reduction of the percentage of times spend in target quadrant of the maze at all time points following the occlusion. Importantly, there were no significant changes in locomotor activity between PBOCCA and sham-operated groups. The BDNF expression in the hippocampus was 29.3±3.1% and 40.1±2.6% on day 14 and 28 post PBOCCA, respectively compared to sham-operated group. Present data suggest that the PBOCCA procedure effectively induces behavioral, cognitive symptoms associated with cerebral ischemia and, consequently, provides a valuable model to study ischemia and related neurodegenerative disorder such as Alzheimer's disease and vascular dementia.
  8. Association of perioperative factor XIII activity levels and other haemostatic markers with the risk of postoperative intracranial haematoma in a selected cohort of neurosurgical patients
    Idris Z, Muzaimi M, Hussin S, Mahmood WH, Abdullah WZ
    Acta Neurochir (Wien), 2012 May;154(5):887-93; discussion 893-4.
    PMID: 22362049 DOI: 10.1007/s00701-012-1296-2
    Coagulation factor XIII and other haemostatic markers are known strengthen fibrin clot formation and, hence, may facilitate safer surgery. Currently however, factor XIII activity levels are not routinely screen. Therefore, the purpose of this study was to determine the association of perioperative factor XIII activity levels and other haemostatic markers with postoperative intracranial haematoma formation in neurosurgical patients.
  9. Neuronavigation-guided endoscopic management of a pineal region tumour with obscured floor of the third ventricle: case report
    Idris Z, Ghani AR, Idris B, Muzaimi M, Awang S, Pal HK, et al.
    Minim Invasive Neurosurg, 2011 Jun;54(3):125-7.
    PMID: 21863520 DOI: 10.1055/s-0031-1277198
    Shunt surgery is frequently chosen to manage periventricular metastasis of pineal region tumours which obscured the floor of the third ventricle. However, this procedure falls short due to distant metastasis. Neuronavigation-guided endoscopic surgery offers a viable alternative.
  10. Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice
    Ismail NIW, Jayabalan N, Mansor SM, Müller CP, Muzaimi M
    Addict Biol, 2017 Jul;22(4):967-976.
    PMID: 26990882 DOI: 10.1111/adb.12385
    Kratom (Mitragyna speciosa) is a widely abused herbal drug preparation in Southeast Asia. It is often consumed as a substitute for heroin, but imposing itself unknown harms and addictive burdens. Mitragynine is the major psychostimulant constituent of kratom that has recently been reported to induce morphine-like behavioural and cognitive effects in rodents. The effects of chronic consumption on non-drug related behaviours are still unclear. In the present study, we investigated the effects of chronic mitragynine treatment on spontaneous activity, reward-related behaviour and cognition in mice in an IntelliCage® system, and compared them with those of morphine and Δ-9-tetrahydrocannabinol (THC). We found that chronic mitragynine treatment significantly potentiated horizontal exploratory activity. It enhanced spontaneous sucrose preference and also its persistence when the preference had aversive consequences. Furthermore, mitragynine impaired place learning and its reversal. Thereby, mitragynine effects closely resembled that of morphine and THC sensitisation. These findings suggest that chronic mitragynine exposure enhances spontaneous locomotor activity and the preference for natural rewards, but impairs learning and memory. These findings confirm pleiotropic effects of mitragynine (kratom) on human lifestyle, but may also support the recognition of the drug's harm potential.
  11. Fulltext Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure
    Tang SP, Kuttulebbai Nainamohamed Salam S, Jaafar H, Gan SH, Muzaimi M, Sulaiman SA
    Oxid Med Cell Longev, 2017;2017:4605782.
    PMID: 28127418 DOI: 10.1155/2017/4605782
    Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase and glutathione-S-transferase. Treatment with Tualang honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.
  12. Fulltext Short-term and long-term survival probabilities among first-ever ischaemic and haemorrhagic stroke patients at a hospital in the suburban east coast of Peninsular Malaysia
    Wan-Arfah N, Hafiz HM, Naing NN, Muzaimi M, Shetty HGM
    Health Sci Rep, 2018 Feb;1(2):e27.
    PMID: 30623059 DOI: 10.1002/hsr2.27
    Aim: This study aimed to determine the 28-day, 1-year, and 5-year survival probabilities in first-ever stroke patients in a relatively understudied setting: a suburban hospital that serves a predominantly rural population in the east coast of Peninsular Malaysia.

    Methods and results: A retrospective record review was conducted among 432 first-ever stroke patients admitted to the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. Data from between January 1, 2005 and December 31, 2011, were extracted from the medical records. The Kaplan-Meier product limit estimator was applied to determine the 28-day, 1-year, and 5-year survival probabilities. Log-rank test was used to test the equality of survival time between different groups. A total of 101 patients died during the study period. The 28-day, 1-year, and 5-year survival probabilities were 78.0% (95% confidence interval [CI]: 73.5-81.9), 74.2% (95% CI: 69.4-78.4), and 70.9% (95% CI: 65.1-75.9), respectively. There were significant differences in the survival time based on the types of stroke, Glasgow Coma Scale, hyperlipidaemia, atrial fibrillation, fasting blood glucose, and diastolic blood pressure.

    Conclusion: This study, though retrospective, highlights several clinical parameters that influenced the survival probabilities among first-ever stroke patients managed in a suburban setting in Malaysia, and compared them to those reported in more urban regions. Our data emphasise the need for wider establishment of specialized stroke units and teams, as well as for prospective multi-centre studies on first-ever stroke patients to better inform the development of stroke care provision in Malaysia.

  13. Determinants of Mortality in First-Ever Stroke Patients in the Suburban Malaysia: A Retrospective Hospital-Based Study, 2005-2011
    Wan-Arfah N, Wan Muhamad Amir WA, Muzaimi M, Mustafa M, Naing NN
    Iran J Public Health, 2015 Sep;44(9):1291-3.
    PMID: 26587506
  14. Fulltext Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts
    Mohd Sairazi NS, Sirajudeen KN, Asari MA, Muzaimi M, Mummedy S, Sulaiman SA
    Evid Based Complement Alternat Med, 2015;2015:972623.
    PMID: 26793262 DOI: 10.1155/2015/972623
    Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.
  15. Fulltext Effect of tualang honey against KA-induced oxidative stress and neurodegeneration in the cortex of rats
    Mohd Sairazi NS, K N S S, Asari MA, Mummedy S, Muzaimi M, Sulaiman SA
    BMC Complement Altern Med, 2017 Jan 09;17(1):31.
    PMID: 28068984 DOI: 10.1186/s12906-016-1534-x
    Administration of KA on rodents has resulted in seizures, behavioral changes, oxidative stress, and neuronal degeneration on selective population of neurons in the brain. The present study was undertaken to investigate the extent of neuroprotective effect conferred by Malaysian Tualang Honey (TH), an antioxidant agent, in the cerebral cortex of rats against KA-induced oxidative stress and neurodegeneration in an animal model of KA-induced excitotoxicity.
  16. Fulltext Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after Kainic Acid-Induced Status Epilepticus
    Mohd Sairazi NS, Sirajudeen KNS, Muzaimi M, Mummedy S, Asari MA, Sulaiman SA
    Evid Based Complement Alternat Med, 2018;2018:7287820.
    PMID: 30108663 DOI: 10.1155/2018/7287820
    The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.
  17. Fulltext LINAC based radiosurgery and radiotherapy for neurosurgical diseases: what have we learnt so far
    Zamzuri I, Badrisyah I, Rahman GI, Pal HK, Muzaimi M, Jafri AM, et al.
    Med J Malaysia, 2011 Oct;66(4):346-9.
    PMID: 22299555 MyJurnal
    Stereotactic radiosurgery uses a single fraction high dose radiation while stereotactic radiotherapy uses multifractionated lower dose focused radiation.
  18. Fulltext Polymodal therapy for high grade gliomas: a case report of favourable outcomes following intraoperative radiation therapy
    Zamzuri I, Rahman GI, Muzaimi M, Jafri AM, Nik Ruzman NI, Lutfi YA, et al.
    Med J Malaysia, 2012 Feb;67(1):121-2.
    PMID: 22582564 MyJurnal
    High grade gliomas, frequently with their infiltrative nature, often make the outcome from neurosurgical intervention alone unsatisfactory. It is recognized that adjuvant radiochemotherapy approaches offer an improved prognosis. For these reasons, we opted for surgical debulking, intraoperative radiation therapy (IORT) in combination with whole brain irradiation therapy and chemotherapy (temozolamide cycles) in the management of a 42 year-old lady with Glioblastoma Multiforme (GBM). Her troublesome symptoms improved after 3 months of this polymodal therapy and remained independently functional for more than two years.
  19. Fulltext Elevated Circulating Microparticle Subpopulations in Incidental Cerebral White Matter Hyperintensities: A Multimodal Study
    Nassir CMNCM, Ghazali MM, Safri AA, Jaffer U, Abdullah WZ, Idris NS, et al.
    Brain Sci, 2021 Jan 20;11(2).
    PMID: 33498429 DOI: 10.3390/brainsci11020133
    Asymptomatic (or "silent") manifestations of cerebral small vessel disease (CSVD) are widely recognized through incidental findings of white matter hyperintensities (WMHs) as a result of magnetic resonance imaging (MRI). This study aims to examine the potential associations of surrogate markers for the evaluation of white matter integrity in CSVD among asymptomatic individuals through a battery of profiling involving QRISK2 cardiocerebrovascular risk prediction, neuroimaging, neurocognitive evaluation, and microparticles (MPs) titers. Sixty asymptomatic subjects (mean age: 39.83 ± 11.50 years) with low to moderate QRISK2 scores were recruited and underwent neurocognitive evaluation for memory and cognitive performance, peripheral venous blood collection for enumeration of selected MPs subpopulations, and 3T MRI brain scan with specific diffusion MRI (dMRI) sequences inclusive of diffusion tensor imaging (DTI). WMHs were detected in 20 subjects (33%). Older subjects (mean age: 46.00 ± 12.00 years) had higher WMHs prevalence, associated with higher QRISK2 score and reduced processing speed. They also had significantly higher mean percentage of platelet (CD62P)- and leukocyte (CD62L)-derived MPs. No association was found between reduced white matter integrity-especially at the left superior longitudinal fasciculus (LSLF)-with age and neurocognitive function; however, LSLF was associated with higher QRISK2 score, total MPs, and CD62L- and endothelial cell-derived MPs (CD146). Therefore, this study establishes these multimodal associations as potential surrogate markers for "silent" CSVD manifestations in the well-characterized cardiocerebrovascular demographic of relatively young, neurologically asymptomatic adults. Furthermore, to the best of our knowledge, this study is the first to exhibit elevated MP counts in asymptomatic CSVD (i.e., CD62P and CD62L), which warrants further delineation.
  20. Fulltext The IntelliCage System: A Review of Its Utility as a Novel Behavioral Platform for a Rodent Model of Substance Use Disorder
    Iman IN, Yusof NAM, Talib UN, Ahmad NAZ, Norazit A, Kumar J, et al.
    Front Behav Neurosci, 2021;15:683780.
    PMID: 34149373 DOI: 10.3389/fnbeh.2021.683780
    The use of animal models for substance use disorder (SUD) has made an important contribution in the investigation of the behavioral and molecular mechanisms underlying substance abuse and addiction. Here, we review a novel and comprehensive behavioral platform to characterize addiction-like traits in rodents using a fully automated learning system, the IntelliCage. This system simultaneously captures the basic behavioral navigation, reward preference, and aversion, as well as the multi-dimensional complex behaviors and cognitive functions of group-housed rodents. It can reliably capture and track locomotor and cognitive pattern alterations associated with the development of substance addiction. Thus, the IntelliCage learning system offers a potentially efficient, flexible, and sensitive tool for the high-throughput screening of the rodent SUD model.
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