Displaying publications 1 - 20 of 142 in total

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  1. Bhatti S, Ali Shah SA, Ahmed T, Zahid S
    Drug Chem Toxicol, 2018 Oct;41(4):399-407.
    PMID: 29742941 DOI: 10.1080/01480545.2018.1459669
    The present study investigates the neuroprotective effects of Foeniculum vulgare seeds in a lead (Pb)-induced brain neurotoxicity mice model. The dried seeds extract of Foeniculum vulgare was prepared with different concentrations of organic solvents (ethanol, methanol, n-hexane). The in vitro antioxidant activity of Foeniculum vulgare seed extracts was assessed through DPPH assay and the chemical composition of the extracts was determined by high-resolution 1H NMR spectroscopy. The age-matched male Balb/c mice (divided into 9 groups) were administered with 0.1% Pb and 75% and 100% ethanol extracts of Foeniculum vulgare seeds at a dose of 200 mg/kg/day and 20 mg/kg/day. The maximum antioxidant activity was found for 75% ethanol extract, followed by 100% ethanol extract. Gene expression levels of oxidative stress markers (SOD1 and Prdx6) and the three isoforms of APP (APP common, 770 and 695), in the cortex and hippocampus of the treated and the control groups were measured. Significant increase in APP 770 expression level while a substantial decrease was observed for SOD1, Prdx6 and APP 695 expression in Pb-treated groups. Interestingly, the deranged expression levels were significantly normalized by the treatment with ethanol extracts of Foeniculum vulgare seeds (specifically at dose of 200 mg/kg/day). Furthermore, the Pb-induced morphological deterioration of cortical neurons was significantly improved by the ethanol extracts of Foeniculum vulgare seeds. In conclusion, the present findings highlight the promising therapeutic potential of Foeniculum vulgare to minimize neuronal toxicity by normalizing the expression levels of APP isoforms and oxidative stress markers.
    Matched MeSH terms: Brain/pathology
  2. Sasongko TH, Ismail NF, Nik Mohd Ariff NA, Zabidi-Hussin ZA
    Jpn J Clin Oncol, 2014 Nov;44(11):1130.
    PMID: 25320338 DOI: 10.1093/jjco/hyu157
    Matched MeSH terms: Brain/pathology*
  3. Chew KM, Sudirman R, Seman N, Yong CY
    Biomed Mater Eng, 2014;24(1):199-207.
    PMID: 24211899 DOI: 10.3233/BME-130800
    The study was conducted based on two objectives as framework. The first objective is to determine the point of microwave signal reflection while penetrating into the simulation models and, the second objective is to analyze the reflection pattern when the signal penetrate into the layers with different relative permittivity, εr. Thus, several microwave models were developed to make a close proximity of the in vivo human brain. The study proposed two different layers on two different characteristics models. The radii on the second layer and the corresponding antenna positions are the factors for both models. The radii for model 1 is 60 mm with an antenna position of 10 mm away, in contrast, model 2 is 10 mm larger in size with a closely adapted antenna without any gap. The layers of the models were developed with different combination of materials such as Oil, Sandy Soil, Brain, Glycerin and Water. Results show the combination of Glycerin + Brain and Brain + Sandy Soil are the best proximity of the in vivo human brain grey and white matter. The results could benefit subsequent studies for further enhancement and development of the models.
    Matched MeSH terms: Brain/pathology*
  4. Candasamy M, Mohamed Elhassan SA, Kumar Bhattamisra S, Hua WY, Sern LM, Binti Busthamin NA, et al.
    Panminerva Med, 2020 Sep;62(3):155-163.
    PMID: 32208408 DOI: 10.23736/S0031-0808.20.03879-3
    Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) are two of the most commonly occurring diseases worldwide, especially among the elderly population. In particular, the increased prevalence of AD has imposed tremendous psychological and financial burdens on society. Growing evidence suggests both AD and T2D share many similar pathological traits. AD is characterized as a metabolic disorder whereby the glucose metabolism in the brain is impaired. This closely resembles the state of insulin resistance in T2D. Insulin resistance of the brain has been heavily implicated two prominent pathological features of AD, Aβ plaques and neurofibrillary tangles. Brain insulin resistance is known to elicit a positive feed-forward loop towards the formation of AD pathology in which they affect each other in a synergistic manner. Other physiological traits shared between the two diseases include inflammation, oxidative stress and autophagic dysfunction, which are also closely associated with brain insulin resistance. In this review and depending on these underlying pathways that link these two diseases, we have discussed the potential therapeutic implications of AD. By expanding our knowledge of the overlapping pathophysiology involved, we hope to provide scientific basis to the discovery of novel therapeutic strategies to improve the clinical outcomes of AD in terms of diagnosis and treatment.
    Matched MeSH terms: Brain/pathology
  5. Acharya UR, Fernandes SL, WeiKoh JE, Ciaccio EJ, Fabell MKM, Tanik UJ, et al.
    J Med Syst, 2019 Aug 09;43(9):302.
    PMID: 31396722 DOI: 10.1007/s10916-019-1428-9
    The aim of this work is to develop a Computer-Aided-Brain-Diagnosis (CABD) system that can determine if a brain scan shows signs of Alzheimer's disease. The method utilizes Magnetic Resonance Imaging (MRI) for classification with several feature extraction techniques. MRI is a non-invasive procedure, widely adopted in hospitals to examine cognitive abnormalities. Images are acquired using the T2 imaging sequence. The paradigm consists of a series of quantitative techniques: filtering, feature extraction, Student's t-test based feature selection, and k-Nearest Neighbor (KNN) based classification. Additionally, a comparative analysis is done by implementing other feature extraction procedures that are described in the literature. Our findings suggest that the Shearlet Transform (ST) feature extraction technique offers improved results for Alzheimer's diagnosis as compared to alternative methods. The proposed CABD tool with the ST + KNN technique provided accuracy of 94.54%, precision of 88.33%, sensitivity of 96.30% and specificity of 93.64%. Furthermore, this tool also offered an accuracy, precision, sensitivity and specificity of 98.48%, 100%, 96.97% and 100%, respectively, with the benchmark MRI database.
    Matched MeSH terms: Brain/pathology*
  6. Ong KC, Badmanathan M, Devi S, Leong KL, Cardosa MJ, Wong KT
    J. Neuropathol. Exp. Neurol., 2008 Jun;67(6):532-42.
    PMID: 18520772 DOI: 10.1097/NEN.0b013e31817713e7
    We describe a model of Enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (CNS) disease. Mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. The mice succumbed to infection after 2 to 5 days. Vacuolated and normal-appearing CNS neurons showed viral RNA and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation was minimal. The most numerous infected neurons were in anterior horns, motor trigeminal nuclei, and brainstem reticular formation; fewer neurons in the red nucleus, lateral cerebellar nucleus, other cranial nerve nuclei, motor cortex, hypothalamus, and thalamus were infected. Other CNS regions, dorsal root, and autonomic ganglia were spared. Intramuscular-inoculated mice killed 24 to 36 hours postinfection had viral RNA and antigens in ipsilateral lumbar anterior horn cells and adjacent axons. Upper cord motor neurons, brainstem, and contralateral motor cortex neurons were infected from 48-72 hours. Viral RNA and antigens were abundant in skeletal muscle and adjacent tissues but not in other organs. The distinct, stereotypic viral distribution in this model suggests that the virus enters the CNS via peripheral motor nerves after skeletal muscle infection, and spread within the CNS involves motor and other neural pathways. This model may be useful for further studies on pathogenesis and for testing therapies.
    Matched MeSH terms: Brain/pathology
  7. Murty OP, Mun K, Gopinath N, Wong KT
    Am J Forensic Med Pathol, 2008 Dec;29(4):364-7.
    PMID: 19259028 DOI: 10.1097/PAF.0b013e3181859ff7
    Every body has to eat to survive but it becomes a matter of great concern, when the life provider food becomes an asphyxiating agent. In this case, a 60-year-old woman choked herself while swallowing biscuits. On autopsy examination, biscuits were found lodged in larygo-pharynx. Brain showed marked dystrophy and loosened lusterless white matter. On histopathologic examination, brain tissue had numerous eosinophilic globules representing astrocytic processes called "Rosenthal fibers"; hence, it was diagnosed as a case of Alexander dystrophy. It is a disease of white matter, where there is a progressive degeneration of the white matter of the brain because of imperfect growth or development of the myelin sheath. The histopathology of brain showed Rosenthal fibers in abundance. This is one of the rarest disease in which choking can occur because of lack of nervous and muscular coordination and weakness. Its specific relation to choking is documented in this report.
    Matched MeSH terms: Brain/pathology
  8. Ong KC, Wong KT
    Brain Pathol, 2015 Sep;25(5):614-24.
    PMID: 26276025 DOI: 10.1111/bpa.12279
    Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance.
    Matched MeSH terms: Brain/pathology
  9. Fu TL, Ong KC, Tan SH, Wong KT
    J. Neuropathol. Exp. Neurol., 2019 12 01;78(12):1160-1170.
    PMID: 31675093 DOI: 10.1093/jnen/nlz103
    Japanese encephalitis (JE) is a known CNS viral infection that often involves the thalamus early. To investigate the possible role of sensory peripheral nervous system (PNS) in early neuroinvasion, we developed a left hindlimb footpad-inoculation mouse model to recapitulate human infection by a mosquito bite. A 1-5 days postinfection (dpi) study, demonstrated focal viral antigens/RNA in contralateral thalamic neurons at 3 dpi in 50% of the animals. From 4 to 5 dpi, gradual increase in viral antigens/RNA was observed in bilateral thalami, somatosensory, and piriform cortices, and then the entire CNS. Infection of neuronal bodies and adjacent nerves in dorsal root ganglia (DRGs), trigeminal ganglia, and autonomic ganglia (intestine, etc.) was also observed from 5 dpi. Infection of explant organotypic whole brain slice cultures demonstrated no viral predilection for the thalamus, while DRG and intestinal ganglia organotypic cultures confirmed sensory and autonomic ganglia susceptibility to infection, respectively. Early thalamus and sensory-associated cortex involvement suggest an important role for sensory pathways in neuroinvasion. Our results suggest that JE virus neuronotropism is much more extensive than previously known, and that the sensory PNS and autonomic system are susceptible to infection.
    Matched MeSH terms: Brain/pathology
  10. Yaiw KC, Ong KC, Chua KB, Bingham J, Wang L, Shamala D, et al.
    J Virol Methods, 2007 Aug;143(2):140-6.
    PMID: 17442409
    Tioman virus is a newly described bat-urine derived paramyxovirus isolated in Tioman Island, Malaysia in 2001. Hitherto, neither human nor animal infection by this virus has been reported. Nonetheless, its close relationship to another paramyxovirus, the Menangle virus which had caused diseases in humans and pigs [Philbey, A.W., Kirkland, P.D., Ross, A.D., Davis, R.J., Gleeson, A.B., Love, R.J., Daniels, P.W., Gould, A.R., Hyatt, A.D., 1998. An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg. Infect. Dis. 4, 269-271], raises the possibility that it may be potentially pathogenic. In this study, mice were experimentally infected with Tioman virus by intraperitoneal and intracerebral routes, and the cellular targets and topographical distribution of viral genome and antigens were examined using in situ hybridization and immunohistochemistry, respectively. The possible association between viral infection and apoptosis was also investigated using the TUNEL assay and immunohistochemistry to FasL, Caspase-3, Caspase-8, Caspase-9 and bcl-2. The results showed that Tioman virus inoculated intracerebrally was neurotropic causing plaque-like necrotic areas, and appeared to preferentially replicate in the neocortex and limbic system. Viral infection of inflammatory cells was also demonstrated. TUNEL and Caspase-3 positivity was found in inflammatory cells but not in neurons, while FasL, Caspase-8 and Caspase-9 were consistently negative. This suggests that neuronal infection was associated with necrosis rather than apoptosis. Moreover, the data suggest that there may be an association between viral infection and apoptosis in inflammatory cells, and that it could, at least in part, involve Caspase-independent pathways. Bcl-2 was expressed in some neurons and inflammatory cells indicating its possible role in anti-apoptosis. There was no evidence of central nervous system infection via the intraperitoneal route.
    Matched MeSH terms: Brain/pathology
  11. Ong KC, Wong KT
    Brain Pathol, 2015 Sep;25(5):605-13.
    PMID: 26276024 DOI: 10.1111/bpa.12278
    The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.
    Matched MeSH terms: Brain/pathology
  12. Barbu MC, Zeng Y, Shen X, Cox SR, Clarke TK, Gibson J, et al.
    PMID: 30197049 DOI: 10.1016/j.bpsc.2018.07.006
    BACKGROUND: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure.

    METHODS: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390).

    RESULTS: We found significantly lower FA in the superior longitudinal fasciculus (β = -.035, pcorrected = .029) and significantly higher MD in a global measure of thalamic radiations (β = .029, pcorrected = .021), as well as higher MD in the superior (β = .034, pcorrected = .039) and inferior (β = .029, pcorrected = .043) longitudinal fasciculus and in the anterior (β = .025, pcorrected = .046) and superior (β = .027, pcorrected = .043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.

    CONCLUSIONS: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts.

    Matched MeSH terms: Brain/pathology*
  13. Aftab MF, Afridi SK, Mughal UR, Karim A, Haleem DJ, Kabir N, et al.
    J. Chem. Neuroanat., 2017 04;81:1-9.
    PMID: 28093241 DOI: 10.1016/j.jchemneu.2017.01.001
    Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration. Methylglyoxal induced stress was inhibited by treatment with URM-II-81. Also, Ser473 and Ser9 phosphorylation of Akt and GSK-3β respectively were restored by URM-II-81. Effect of URM-II-81 on axonal integrity was studied by differentiating Neuro2A using retinoic acid. URM-II-81 restored axonal length in MGO treated cells. Its effects were also studied in high fat and low dose streptozotocin induced diabetic mice where it reduced RBG levels and inhibited glycative stress by reducing HbA1c. URM-II-81 treatment also showed inhibition of gliosis in hippocampus. Histological analysis showed reduced NFTs in CA3 hippocampal region and restoration of insulin signaling in hippocampii of diabetic mice. Our findings suggest that URM-II-81 can be developed as a new therapeutic agent for treatment of neurodegenration.
    Matched MeSH terms: Brain/pathology
  14. Koh KL, Sonny Teo KS, Halim SA, Wan Hitam WH
    Can J Ophthalmol, 2019 04;54(2):e66-e69.
    PMID: 30975364 DOI: 10.1016/j.jcjo.2018.06.022
    Matched MeSH terms: Brain/pathology*
  15. Junaid QO, Khaw LT, Mahmud R, Ong KC, Lau YL, Borade PU, et al.
    Parasite, 2017;24:38.
    PMID: 29034874 DOI: 10.1051/parasite/2017040
    BACKGROUND: As the quest to eradicate malaria continues, there remains a need to gain further understanding of the disease, particularly with regard to pathogenesis. This is facilitated, apart from in vitro and clinical studies, mainly via in vivo mouse model studies. However, there are few studies that have used gerbils (Meriones unguiculatus) as animal models. Thus, this study is aimed at characterizing the effects of Plasmodium berghei ANKA (PbA) infection in gerbils, as well as the underlying pathogenesis.

    METHODS: Gerbils, 5-7 weeks old were infected by PbA via intraperitoneal injection of 1 × 106 (0.2 mL) infected red blood cells. Parasitemia, weight gain/loss, hemoglobin concentration, red blood cell count and body temperature changes in both control and infected groups were monitored over a duration of 13 days. RNA was extracted from the brain, spleen and whole blood to assess the immune response to PbA infection. Organs including the brain, spleen, heart, liver, kidneys and lungs were removed aseptically for histopathology.

    RESULTS: Gerbils were susceptible to PbA infection, showing significant decreases in the hemoglobin concentration, RBC counts, body weights and body temperature, over the course of the infection. There were no neurological signs observed. Both pro-inflammatory (IFNγ and TNF) and anti-inflammatory (IL-10) cytokines were significantly elevated. Splenomegaly and hepatomegaly were also observed. PbA parasitized RBCs were observed in the organs, using routine light microscopy and in situ hybridization.

    CONCLUSION: Gerbils may serve as a good model for severe malaria to further understand its pathogenesis.

    Matched MeSH terms: Brain/pathology
  16. Zainuddin NM, Sthaneshwar P, Vethakkan SRDB
    Malays J Pathol, 2019 Dec;41(3):369-372.
    PMID: 31901925
    INTRODUCTION: Hyponatraemia is one of the most frequent laboratory findings in hospitalised patients. We present an unusual case of hyponatraemia in a 23-year-old female secondary to acute intermittent porphyria (AIP), a rare inborn error of metabolism.

    CASE REPORT: The patient presented with upper respiratory tract infection, fever, seizures and abdominal pain. An initial diagnosis of encephalitis was made. In view of the unexplained abdominal pain with other clinical findings such as posterior reversible encephalopathy syndrome by CT brain, temporary blindness as well as hyponatraemia, acute intermittent porphyria was suspected. Urine delta aminolaevulinic acid (δ-ALA) and porphobilinogen were elevated confirming the diagnosis of AIP. Genetic studies were done for this patient. The patient had a complete resolution of her symptoms with carbohydrate loading and high caloric diet.

    CONCLUSION: Although rare, AIP should be considered as a cause of hyponatraemia in a patient who presents with signs and/or symptoms that are characteristic of this disease.

    Matched MeSH terms: Brain/pathology
  17. Vanselow BA
    Vet Rec, 1980 Jul 05;107(1):15-8.
    PMID: 7434536
    A severe epizootic of bovine malignant catarrh occurred from November 1976 until June 1977 in cattle at an agricultural institute in peninsular Malaysia. In a group of 82 Kedah-Kelantan cattle the morbidity rate was 47.6 per cent with a fatality rate of 89.7 per cent. In a group of 43 local Indian dairy cattle the morbidity rate was 23.3 per cent with a fatality rate of 100 per cent. Although evidence suggested that sheep acted as a common source of infection, the disease occurred in one animal which had no contact with sheep but had contact with infected cattle and carcases.
    Matched MeSH terms: Brain/pathology
  18. Hinson VK, Tyor WR
    Curr. Opin. Neurol., 2001 Jun;14(3):369-74.
    PMID: 11371762
    Over 100 viruses have been associated with acute central nervous system infections. The present review focuses on some of the most common agents of viral encephalitis, as well as important emerging viral encephalitides. In this context, the initial detection of West Nile virus in the Western Hemisphere during the 1999 New York City outbreak, the first description of Nipah virus in Malaysia, and the appearance in Asia of a new neurovirulent enterovirus 71 strain that causes severe neurologic disease are highlighted. In addition, advances regarding diagnosis, neuroimaging and treatment of Japanese and herpes simplex encephalitis are presented.
    Matched MeSH terms: Brain/pathology
  19. Waran V, Chandran H, Devaraj P, Ravindran K, Rathinam AK, Balakrishnan YK, et al.
    J Neurol Surg A Cent Eur Neurosurg, 2014 Nov;75(6):422-6.
    PMID: 23955263 DOI: 10.1055/s-0033-1345091
    The universal probe is a tool devised to allow navigation-directed biopsies and drainage procedures to be performed in a simple manner using a single hardware and software.
    Matched MeSH terms: Brain/pathology
  20. Ishiura H, Shibata S, Yoshimura J, Suzuki Y, Qu W, Doi K, et al.
    Nat Genet, 2019 08;51(8):1222-1232.
    PMID: 31332380 DOI: 10.1038/s41588-019-0458-z
    Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.
    Matched MeSH terms: Brain/pathology*
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