Publications by authors named "Mazira Mohamad Ghazali"

10 Publications

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Diets and Cellular-Derived Microparticles: Weighing a Plausible Link With Cerebral Small Vessel Disease.

Front Cardiovasc Med 2021 24;8:632131. Epub 2021 Feb 24.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

Cerebral small vessel disease (CSVD) represents a spectrum of pathological processes of various etiologies affecting the brain microcirculation that can trigger neuroinflammation and the subsequent neurodegenerative cascade. Prevalent with aging, CSVD is a recognized risk factor for stroke, vascular dementia, Alzheimer disease, and Parkinson disease. Despite being the most common neurodegenerative condition with cerebrocardiovascular axis, understanding about it remains poor. Interestingly, modifiable risk factors such as unhealthy diet including high intake of processed food, high-fat foods, and animal by-products are known to influence the non-neural peripheral events, such as in the gastrointestinal tract and cardiovascular stress through cellular inflammation and oxidation. One key outcome from such events, among others, includes the cellular activations that lead to elevated levels of endogenous cellular-derived circulating microparticles (MPs). MPs can be produced from various cellular origins including leukocytes, platelets, endothelial cells, microbiota, and microglia. MPs could act as microthrombogenic procoagulant that served as a plausible culprit for the vulnerable end-artery microcirculation in the brain as the end-organ leading to CSVD manifestations. However, little attention has been paid on the potential role of MPs in the onset and progression of CSVD spectrum. Corroboratively, the formation of MPs is known to be influenced by diet-induced cellular stress. Thus, this review aims to appraise the body of evidence on the dietary-related impacts on circulating MPs from non-neural peripheral origins that could serve as a plausible microthrombosis in CSVD manifestation as a precursor of neurodegeneration. Here, we elaborate on the pathomechanical features of MPs in health and disease states; relevance of dietary patterns on MP release; preclinical studies pertaining to diet-based MPs contribution to disease; MP level as putative surrogates for early disease biomarkers; and lastly, the potential of MPs manipulation with diet-based approach as a novel preventive measure for CSVD in an aging society worldwide.
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http://dx.doi.org/10.3389/fcvm.2021.632131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943466PMC
February 2021

Elevated Circulating Microparticle Subpopulations in Incidental Cerebral White Matter Hyperintensities: A Multimodal Study.

Brain Sci 2021 Jan 20;11(2). Epub 2021 Jan 20.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.

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.
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http://dx.doi.org/10.3390/brainsci11020133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909442PMC
January 2021

Cerebral Small Vessel Disease (CSVD) - Lessons From the Animal Models.

Front Physiol 2019 24;10:1317. Epub 2019 Oct 24.

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.

Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and imaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. Unlike large vessels, it is a challenge to visualize small vessels , hence the difficulty to directly monitor the natural progression of the disease. CSVD might progress for many years during the early stage of the disease as it remains asymptomatic. Prevalent among elderly individuals, CSVD has been alarmingly reported as an important precursor of full-blown stroke and vascular dementia. Growing evidence has also shown a significant association between CSVD's radiological manifestation with dementia and Alzheimer's disease (AD) pathology. Although it remains contentious as to whether CSVD is a cause or sequelae of AD, it is not far-fetched to posit that effective therapeutic measures of CSVD would mitigate the overall burden of dementia. Nevertheless, the unifying theory on the pathomechanism of the disease remains elusive, hence the lack of effective therapeutic approaches. Thus, this chapter consolidates the contemporary insights from numerous experimental animal models of CSVD, to date: from the available experimental animal models of CSVD and its translational research value; the pathomechanical aspects of the disease; relevant aspects on systems biology; opportunities for early disease biomarkers; and finally, converging approaches for future therapeutic directions of CSVD.
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http://dx.doi.org/10.3389/fphys.2019.01317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822570PMC
October 2019

Functional outcome at 6 months in surgical treatment of spontaneous supratentorial intracerebral haemorrhage.

Malays J Med Sci 2008 Oct;15(4):48-55

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia.

A prospective cohort study was done to evaluate the role of surgery in patients with spontaneous supratentorial intracerebral haemorrhage (SICH) and to identify predictors of outcome including the use of invasive regional cortical cerebral blood flow (rCoBF) and microdialysis. Surgery consisted of craniotomy or decompressive craniectomy. The ventriculostomy for intracranial pressure (ICP) monitoring and drainage and regional cortical cerebral blood flow (rCoBF) and microdialysis were performed in all subjects. Pre and post operative information on subjects were collected. The study end points was functional outcome at 6 months based on a dichotomised Glasgow Outcome Scale (GOS).The selected clinical, radiological, biochemical and treatment factors that may influence the functional outcome were analysed for their significance. A total of 36 patients were recruited with 27(75%) patients had Glasgow Coma Score (GCS) between 5 to 8 on admission and 9(25%) were admitted with GCS of 9. At 6 months, 86 % had a poor or unfavourable outcome (GOS I-III) and 14% had good or favourable outcome (GOS IV-V). The mortality rate at 6 months was 55%. Univariate analysis for the functional outcome identified 2 significant variables, the midline shift (p=0.013) and mean lactate:pyruvate ratio (p=0.038). Multivariate analysis identified midline shift as the single significant independent predictor of functional outcome (p=0.013).Despite aggressive regional cortical cerebral blood flow (rCoBF) and microdialysis study for detection of early ischemia, surgical treatment for spontaneous intracerebral haemorrhage only benefited a small number of patients in terms of favourable outcome (14%) and in the majority of patients (86%), the outcome was unfavourable. Patients with midline shift > 5mm has almost 21 times higher chances (adj) OR 20.8 of being associated with poor outcome (GOS I-III).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341921PMC
October 2008

Molecular genetic analysis of BAX and cyclin D1 genes in patients with malignant glioma.

Neurol Res 2007 Apr;29(3):239-42

Department of Neurosciences, Department of Pathology, and Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

Introduction And Objectives: Brain tumorigenesis is a complex process involving multiple genetic alterations. Cyclin D1 and BAX genes are two of the most important regulators in controlling the normal proliferation and apoptosis of cells, respectively. In this study, we analysed the possibilities of involvement of cyclin D1 and BAX genes in the gliomagenesis.

Methods And Results: In determining gene alterations of exon 4 of cyclin D1 gene and exon 6 of BAX gene, all samples were amplified by polymerase chain reaction (PCR) and subsequently by direct sequencing. Our results showed a frameshift mutation (G base deletion) at nucleotide 82 of codon 28 in exon 4 of the cyclin D1 gene and another frameshift mutation with a deletion of C base at nucleotide 153 of exon 6 of the BAX gene in two separate cases of a glioblastoma multiform (WHO Grade IV) sample.

Conclusion: These findings suggest that both cyclin D1 and BAX genes alteration are rarely found in brain tumors. However, the alteration might cause a significant effect of the normal protein production and this might contribute to the development of brain tumorigenesis in Malaysian patients.
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http://dx.doi.org/10.1179/016164107X158965DOI Listing
April 2007

Association of loss of heterozygosity and PTEN gene abnormalities with paraclinical, clinical modalities and survival time of glioma patients in Malaysia.

Asian J Surg 2006 Oct;29(4):274-82

Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

Background: The pattern of allelic loss of heterozygosity (LOH) and PTEN mutations appear to be associated with the progression of gliomas leading to a decrement in the survival rate of patients. This present study was carried out to determine the LOH and PTEN mutational status in glioma patients and its association with patients' survival.

Methods: Thirty-seven Malaysian glioma patients of the Malay race were subject to PTEN mutational analysis and the presence of LOH using the cold single-strand conformation polymorphism method, and their clinical and paraclinical response were correlated.

Results: Among analysed glioma patients, seven (21.6%) cases with PTEN mutations were detected and 12 (32.4%) of 37 patients showed presence of LOH. Univariate analysis showed that tumour grade, vascularization, PTEN mutation, LOH and combination of both PTEN mutation and LOH were significantly associated with glioma patients' survival. Multivariate analysis revealed that no factors contributed to survival time.

Conclusion: The results show that PTEN mutation and LOH are quite frequent in Malaysian glioma patients. However, they have no impact on the survival outcome of patients.
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http://dx.doi.org/10.1016/S1015-9584(09)60102-0DOI Listing
October 2006

Persistence of cognitive deficits following paediatric head injury without professional rehabilitation in rural East Coast Malaysia.

Asian J Surg 2005 Jul;28(3):163-7

Department of Neurosciences, School of Medical Sciences and Hospital Universiti Sains Malaysia, Kelantan, Malaysia.

Objective: To use data from a prospective, longitudinal study to determine whether psychomotor functions improve spontaneously during the first year following paediatric traumatic brain injury without modern rehabilitation facilities in a rural area of Malaysia.

Methods: Thirty-six paediatric patients who were referred for neurosurgical management for mild to severe head injuries were studied over a period of 2 years. No patients had orthopaedic or surgical trauma. Assessment of patients occurred at 3, 6 and 12 months, and patients were subjected to the Bender Gestalt Test, Weschler Intelligence Scale for Children--Revised and subtests from the Weschler Preschool and Primary Scale of Intelligence. None of the patients received professional rehabilitation due to a lack of facilities; only traditional treatment was given during this period.

Results: There were no significant changes in any of the parameters, except for integration error, after a period of 1 year. Cognitive function improved in 30% of patients after 1 year of follow-up. Despite an increased relationship of the caregiver to the patient in the first year of trauma, there was no general improvement when compared to the Western literature.

Conclusion: A lack of modern resources in the community, a low general practitioner to patient ratio, and no inpatient or outpatient rehabilitation services do not lead to spontaneous improvement in the psychomotor condition of our patients despite good interfamily support. These are important findings for the future restructuring of the psychological service in Malaysia.
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http://dx.doi.org/10.1016/S1015-9584(09)60334-1DOI Listing
July 2005

Extradural spinal schwannoma in 12 year old child : a case report.

Malays J Med Sci 2005 Jul;12(2):60-3

Department of Neurosciences.

We report a case of a 12 year old girl who presented with cord compression. Imaging studies demonstrated an extradural spinal tumour in the lower thoracic and upper lumbar levels. Histology confirmed the diagnosis of schwannoma while associated findings suggested the possibility of Neurofibromatosis Type I.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349403PMC
July 2005

Outcome of severe traumatic brain injury: comparison of three monitoring approaches.

Neurosurg Focus 2003 Dec 15;15(6):E1. Epub 2003 Dec 15.

Department of Anesthesiology and Critical Care Medicine, and Neurosciences and Biostatistic Unit, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

The determination of cerebral perfusion pressure (CPP) is regarded as vital in monitoring patients with severe traumatic brain injury. Besides indicating the status of cerebral blood flow (CBF), it also reveals the status of intracranial pressure (ICP). The abnormal or suboptimal level of CPP is commonly correlated with high values of ICP and therefore with poor patient outcomes. Eighty-two patients were divided into three groups of patients receiving treatment based on CPP and CBF, ICP alone, and conservative methods during two different observation periods. The characteristics of these three groups were compared based on age, sex, time between injury and hospital arrival, Glasgow Coma Scale score, pupillary reaction to light, surgical intervention, and computerized tomography scanning findings according to the Marshall classification system. Only time between injury and arrival (p = 0.001) was statistically significant. There was a statistically significant difference in the proportions of good outcomes between the multimodality group compared with the group of patients that underwent a single intracranial-based monitoring method and the group that received no monitoring (p = 0.003) based on a disability rating scale after a follow up of 12 months. Death was the focus of outcome in this study in which the multimodality approach to monitoring had superior results.
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http://dx.doi.org/10.3171/foc.2003.15.6.1DOI Listing
December 2003

Molecular genetic analysis of anaplastic pleomorphic xanthoastrocytoma.

Asian J Surg 2003 Apr;26(2):120-5

Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.

A case of pleomorphic xanthoastrocytoma in a 10-year-old Malay boy is reported. The patient presented with headache and epilepsy. On computed tomography, a ring-enhancing low-density lesion was observed in the left fronto-temporal area. During surgery, a cystic tumour containing serous fluid was found and almost totally removed. Histologically, the tumour exhibited marked pleomorphism of oval and spindle-shaped cells intermixed with uni- and multinucleated giant cells, and xanthomatous cells with foamy cytoplasm. The tumour displayed pericellular reticulin and periodic acid-Schiff positive granules. Focally, six mitotic characters per 10 high-power fields were seen, and necrosis was confined only to the inner lining of the cyst. Mutational analysis showed that a frameshift mutation (a 4-bp deletion) in the p53 gene had occurred in codons 273 and 274 of exon 8. No mutation was detected in the p16 gene. No allelic loss and/or loss of heterozygosity were observed on chromosome 10 using microsatellite marker D105532. The patient was treated with postoperative radiotherapy because of histological anaplasia and the presence of residual tumour. The patient showed marked neurological recovery after a follow-up period of 2 years.
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http://dx.doi.org/10.1016/S1015-9584(09)60233-5DOI Listing
April 2003