MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches

Chiroma SM, Hidayat Baharuldin MT, Mat Taib CN, Amom Z, Jagadeesan S, Adenan MI, et al.

Biomed Pharmacother, 2019 Jan;109:853-864.
PMID: 30551539 DOI: 10.1016/j.biopha.2018.10.111

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats.
MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.
RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.
CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.

Matched MeSH terms: Mild Cognitive Impairment/pathology
MRI Markers of Mixed Pathology and Cognitive Impairment in Multiethnic Asians

Tan CH, Hilal S, Xu X, Vrooman H, Cheng CY, Wong TY, et al.

J Alzheimers Dis, 2020;73(4):1501-1509.
PMID: 31958085 DOI: 10.3233/JAD-190866

There is a need to elucidate the combined influence of neurodegeneration and cerebrovascular disease (CeVD) on cognitive impairment, especially in diverse populations. Here, we evaluated 840 multiethnic individuals (mean age = 70.18) across the disease spectrum from the Epidemiology of Dementia in Singapore study. First, we determined whether a validated quantitative MRI score of mixed pathology is associated with clinical diagnosis and whether the score differed between ethnicities (Chinese, Malays, and Indians). We then evaluated whether the score was associated with multidomain cognitive impairment and if additional measures of CeVD were further associated with cognitive impairment. We found that lower quantitative MRI scores were associated with severity of clinical diagnosis and Chinese individuals had the highest quantitative MRI scores, followed by Indians and Malays. Lower quantitative MRI scores were also associated with lower performance in attention, language, visuoconstruction, visuomotor, visual, and verbal memory domains. Lastly, the presence of intracranial stenosis and cortical cerebral microinfarcts, but not cerebral microbleeds, were associated with memory performance beyond quantitative MRI scores. Taken together, our results demonstrate the utility of using multiple MRI markers of neurodegeneration and CeVD for identifying multiethnic Asians with the greatest cognitive impairment due to mixed pathology.

Matched MeSH terms: Mild Cognitive Impairment/pathology*
Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease

Mihardja M, Roy J, Wong KY, Aquili L, Heng BC, Chan YS, et al.

Ann N Y Acad Sci, 2020 10;1478(1):43-62.
PMID: 32700392 DOI: 10.1111/nyas.14436

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.

Matched MeSH terms: Mild Cognitive Impairment/pathology
Clinical, semiological, electroencephalographic, and neuropsychological features of "pure" neocortical temporal lobe epilepsy

Maizuliana H, Usui N, Terada K, Kondo A, Inoue Y

Epileptic Disord, 2020 Feb 01;22(1):55-65.
PMID: 32031536 DOI: 10.1684/epd.2020.1132

We examined the clinical, semiological, scalp EEG, and neuropsychological features of patients with "pure" neocortical temporal lobe epilepsy (NTLE) who were successfully treated by neocortical temporal resection sparing the mesial temporal structures. This retrospective study included 17 patients with lesional NTLE who satisfied the following criteria: presence of a discrete structural lesion in the lateral temporal lobe on preoperative MRI; lateral temporal resection sparing the mesial temporal structures; follow-up for at least two years after surgery; and favourable postoperative seizure outcome (Engel Class I). The study included 10 females and seven males, and the age at surgery ranged from 15 to 48 years (mean: 30.7 years). Auras, video-recorded seizure semiology, interictal and ictal EEG, and pre- and post-operative neuropsychological data were reviewed. Twenty patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, who had a favourable postoperative seizure outcome (Engel Class I), were selected as a control group. Age at seizure onset was significantly greater in patients with NTLE than in controls. A history of febrile convulsion was significantly less frequent in NTLE patients. Epigastric ascending sensation (6% versus 40%; p=0.017), oral automatisms (29% versus 80%; p=0.003), gestural automatisms (47% versus 80%; p=0.047), and dystonic posturing (0% versus 40%; p=0.003) were significantly less frequent in NTLE than controls. Ictal unitemporal rhythmic theta activity was also significantly less frequent in NTLE than controls (35.3% versus 75%; p=0.015). Preoperative IQ score (range: 68 to 114; mean: 88.9) and preoperative memory quotient score (range: 56-122; mean: 98.1) were significantly higher in NTLE (p=0.003 and p=0.048, respectively). There were notable differences in clinical, semiological, EEG, and neuropsychological features between "pure" NTLE and MTLE. These findings may be useful to identify the epileptogenic zone.

Matched MeSH terms: Mild Cognitive Impairment/pathology
The Association Between Visual Field Reliability Indices and Cognitive Impairment in Glaucoma Patients

Raman P, Khy Ching Y, Sivagurunathan PD, Ramli N, Mohd Khalid KH

J Glaucoma, 2019 08;28(8):685-690.
PMID: 31033782 DOI: 10.1097/IJG.0000000000001269

PRECIS: This prospective cross-sectional study found that patients with cognitive impairment (CI) are more likely to produce unreliable visual field (VF) tests, especially with higher false-negative (FN) responses and consequent overestimation of mean deviation (MD).
AIM: Aging-associated CI can impair the ability of individuals to perform a VF test and compromise the reliability of the results. We evaluated the association between neurocognitive impairment and VF reliability indices in glaucoma patients.
METHODS: This prospective, cross-sectional study was conducted in the Ophthalmology Department, Hospital Kuala Pilah, Malaysia, and included 113 eyes of 60 glaucoma patients with no prior diagnosis of dementia. Patients were monitored with the Humphrey Visual Field Analyzer using a 30-2 SITA, standard protocol, and CI was assessed using the clock drawing test (CDT). The relationships between the CDT score, MD, pattern standard deviation, Visual Field Index (VFI), fixation loss (FL), false-positive values, and FN values were analyzed using the ordinal regression model.
RESULTS: Glaucoma patients older than 65 years had a higher prevalence of CI. There was a statistically significant correlation between CDT scores and glaucoma severity, FL, FN, and VFI values (rs=-0.20, P=0.03; rs=-0.20, P=0.04; rs=-0.28, P=0.003; rs=0.21, P=0.03, respectively). In a multivariate model adjusted for age and glaucoma severity, patients with lower FN were significantly less likely to have CI (odds ratio, 0.91; 95% confidence interval, 0.89-0.93) and patients with higher MD were more likely to have CI (odds ratio, 1.10; 95% confidence interval, 1.05-1.16); false positive, FL, pattern standard deviation, and VFI showed no significant correlation.
CONCLUSION: Cognitive decline is associated with reduced VF reliability, especially with higher FN rate and overestimated MD. Screening and monitoring of CI may be important in the assessment of VF progression in glaucoma patients.

Matched MeSH terms: Mild Cognitive Impairment/pathology
d-galactose and aluminium chloride induced rat model with cognitive impairments

Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z

Biomed Pharmacother, 2018 Jul;103:1602-1608.
PMID: 29864948 DOI: 10.1016/j.biopha.2018.04.152

Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer's disease (AD). d-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg.bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyperphosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.

Matched MeSH terms: Mild Cognitive Impairment/pathology*
Fulltext Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

Bhuvanendran S, Bakar SNS, Kumari Y, Othman I, Shaikh MF, Hassan Z

Sci Rep, 2019 10 10;9(1):14507.
PMID: 31601902 DOI: 10.1038/s41598-019-50954-y

Alzheimer's disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.

Matched MeSH terms: Mild Cognitive Impairment/pathology