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Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's disease

Gnanasegaran N, Govindasamy V, Mani V, Abu Kasim NH

IUBMB Life, 2017 09;69(9):689-699.
PMID: 28685937 DOI: 10.1002/iub.1655

In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons. Assessments were performed on their proliferation, extent of DNA damage, productions of reactive oxygen species (ROS) and nitric oxide (NO), as well as secretion of inflammatory mediators. Notably, DPSCs were shown to attenuate their proliferation, production of ROS, and NO significantly (P

Matched MeSH terms: Dopaminergic Neurons/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: Neurons/pathology
Fulltext Deaths of children during an outbreak of hand, foot, and mouth disease in Sarawak, Malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group

Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, et al.

Clin Infect Dis, 2000 Sep;31(3):678-83.
PMID: 11017815

From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.

Matched MeSH terms: Neurons/pathology
Oestradiol effects on neuroendocrine responses induced by water deprivation in rats

Vilhena-Franco T, Mecawi AS, Elias LL, Antunes-Rodrigues J

J Endocrinol, 2016 Nov;231(2):167-180.
PMID: 27613338

Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression.

Matched MeSH terms: Neurons/pathology
Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells

Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL

J Ethnopharmacol, 2018 May 10;217:187-194.
PMID: 29462698 DOI: 10.1016/j.jep.2018.02.025

ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity.
MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.
RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.
CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Matched MeSH terms: Neurons/pathology
Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons

Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, et al.

Cell Mol Neurobiol, 2013 Nov;33(8):1159-69.
PMID: 24101432 DOI: 10.1007/s10571-013-9982-z

Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has demonstrated several neuropharmacological attributes. In the present study, the neuroprotective properties of TQ were investigated by studying its anti-apoptotic potential to diminish β-amyloid peptide 1-40 sequence (Aβ1-40)-induced neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The effects of TQ against Aβ1-40-induced neurotoxicity, morphological damages, DNA condensation, the generation of reactive oxygen species, and caspase-3, -8, and -9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 μM) and subsequent exposure to 10 μM Aβ1-40 protected the CGNs against the neurotoxic effects of the latter. In addition, the CGNs were better preserved with intact cell bodies, extensive neurite networks, a loss of condensed chromatin and less free radical generation than those exposed to Aβ1-40 alone. TQ pretreatment inhibited Aβ1-40-induced apoptosis of CGNs via both extrinsic and intrinsic caspase pathways. Thus, the findings of this study suggest that TQ may prevent neurotoxicity and Aβ1-40-induced apoptosis. TQ is, therefore, worth studying further for its potential to reduce the risks of developing Alzheimer's disease.

Matched MeSH terms: Neurons/pathology*
Fulltext Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome

Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.

PLoS One, 2020;15(7):e0236826.
PMID: 32730314 DOI: 10.1371/journal.pone.0236826

Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.

Matched MeSH terms: Neurons/pathology*
Fulltext Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study

Chai X, Low KY, Tham YC, Chee ML, Thakur S, Zhang L, et al.

Invest Ophthalmol Vis Sci, 2020 08 03;61(10):37.
PMID: 32821913 DOI: 10.1167/iovs.61.10.37

Purpose: Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness.
Methods: A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED) study, a population-based study composing of three major ethnic groups-Malay, Indian, and Chinese-in Singapore. Ocular examinations were performed, and spectral-domain optical coherence tomography (SD-OCT) was used to measure circumpapillary RNFL thickness. We selected 35 independent glaucoma-associated genetic loci for analysis. An linear regression model was conducted to determine the association of these variants with circumpapillary RNFL, assuming an additive genetic model. We conducted association analysis in each of the three ethnic groups, followed by a meta-analysis of them.
Results: The mean age of the included participants was 59.4 ± 8.9 years, and the mean RFNL thickesss is 92.3 ± 11.2 µm. In the meta-analyses, of the 35 glacuoma loci, we found that only SIX6 was significantly associated with reduction in global RNFL thickness (rs33912345; β = -1.116 um per risk allele, P = 1.64E-05), and the effect size was larger in the inferior RNFL quadrant (β = -2.015 µm, P = 2.9E-6), and superior RNFL quadrant (β = -1.646 µm, P = 6.54E-5). The SIX6 association were consistently observed across all three ethnic groups. Other than RNFL, we also found several genetic varaints associated with vertical cuo-to-disc ratio (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7), rim area (SIX6 and CDKN2B-AS1), and disc area (SIX6, ATOH7, and TGFBR3-CDC7). The association of SIX6 rs33912345 with NRFL thickness remained similar after further adjusting for disc area and 3 other disc parameter associated SNPs (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7).
Conclusions: Of the 35 glaucoma identified risk loci, only SIX6 is significantly and independently associated with thinner RNFL. Our study further supports the involvement of SIX6 with RNFL thickness and pathogensis of glaucoma.

Matched MeSH terms: Retinal Neurons/pathology*
Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions

Lai SSM, Ng KY, Koh RY, Chok KC, Chye SM

Metab Brain Dis, 2021 08;36(6):1087-1100.
PMID: 33881723 DOI: 10.1007/s11011-021-00737-0

The endosomal-lysosomal system mediates the process of protein degradation through endocytic pathway. This system consists of early endosomes, late endosomes, recycling endosomes and lysosomes. Each component in the endosomal-lysosomal system plays individual crucial role and they work concordantly to ensure protein degradation can be carried out functionally. Dysregulation in the endosomal-lysosomal system can contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). In AD endosomal-lysosomal abnormalities are the earliest pathological features to note and hence it is important to understand the involvement of endosomal-lysosomal dysfunction in the pathogenesis of AD. In-depth understanding of this dysfunction can allow development of new therapeutic intervention to prevent and treat AD.

Matched MeSH terms: Neurons/pathology
Fulltext A golden hamster model for human acute Nipah virus infection

Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange M, Bernard A, et al.

Am J Pathol, 2003 Nov;163(5):2127-37.
PMID: 14578210 DOI: 10.1016/S0002-9440(10)63569-9

A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153-2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection.

Matched MeSH terms: Neurons/pathology
Fulltext Relationship between anthropometric and biochemical changes of metabolic syndrome with retinal nerve fiber layer and macular thickness

New SH, Leow SN, Vasudevan SK, Idris IB, Tang SF, Din NM

PLoS One, 2021;16(2):e0246830.
PMID: 33630879 DOI: 10.1371/journal.pone.0246830

OBJECTIVE: To evaluate the retinal nerve fiber layer (RNFL) and macular thicknesses and identify systemic risk factors for thinning of these layers in patients with metabolic syndrome (MetS).
METHODOLOGY: A cross-sectional observational study was performed on patients diagnosed with MetS and compared to normal controls. All patients underwent ophthalmic and anthropometric examination, serological and biochemical blood investigations; and ocular imaging using spectral-domain optical coherence tomography. Patients with ocular pathology were excluded. Unpaired t-test was used to compare mean thickness between the two groups. One-way ANOVA with Bonferroni correction for multiple comparisons was used to compare mean thickness between different tertiles of MetS parameters, and a generalized estimating equation was used to correct for inter-eye correlation and to assess association between mean thickness and covariates.
RESULTS: Two hundred and forty-eight eyes from 124 participants (1:1 ratio of MetS patients to controls) were included. Age ranged between 30 to 50 years old, and mean age was 40 ± 6.6 years. RNFL thickness was lower globally (93.6 ± 9.9 μm vs 99.0 ± 9.3, p<0.001) and in the inferior (124.5 ± 17.5 μm vs 131.0 ± 16.4 μm, p = 0.002), superior (117.2 ± 16.0 μm vs 126.3 ± 14.4 μm, p<0.001) and temporal (65.5 ± 10.2 μm vs 69.5 ± 9.8, p = 0.002) sectors in MetS patients compared to controls. Only the central (237.0 ± 14.0 μm vs 243.6 ± 18.0 μm, p = 0.002) and inferior parafoveal (307.8 ± 20.9 vs 314.6 ± 14.6, p = 0.004) area of the macula was significantly thinner. The inferior RNFL sector had the most difference (mean difference = 9.1 μm). The Generalized Estimating Equation found that, after adjusting for age, diastolic blood pressure, BMI, HDL and obesity; the number of MetS components and elevated triglyceride levels were independent risk factors for reduced thickness in global RNFL (β = -4.4, 95% CI = -7.29 to -1.5, p = 0.003) and inferior parafovea (β = -6.85, 95% CI = -11.58 to -2.13, p = 0.004) thickness respectively.
CONCLUSION: RNFL thinning was seen more than macula thinning in MetS patients, suggesting RNFL susceptibility to neurodegeneration than the macula. A higher number of metabolic components and elevated triglyceride levels were independent risk factors for retinal thinning in this group of patients.

Matched MeSH terms: Retinal Neurons/pathology*
The Role of Neuronal NLRP1 Inflammasome in Alzheimer's Disease: Bringing Neurons into the Neuroinflammation Game

Yap JKY, Pickard BS, Chan EWL, Gan SY

Mol Neurobiol, 2019 Nov;56(11):7741-7753.
PMID: 31111399 DOI: 10.1007/s12035-019-1638-7

The innate immune system and inflammatory response in the brain have critical impacts on the pathogenesis of many neurodegenerative diseases including Alzheimer's disease (AD). In the central nervous system (CNS), the innate immune response is primarily mediated by microglia. However, non-glial cells such as neurons could also partake in inflammatory response independently through inflammasome signalling. The NLR family pyrin domain-containing 1 (NLRP1) inflammasome in the CNS is primarily expressed by pyramidal neurons and oligodendrocytes. NLRP1 is activated in response to amyloid-β (Aβ) aggregates, and its activation subsequently cleaves caspase-1 into its active subunits. The activated caspase-1 proteolytically processes interleukin-1β (IL-1β) and interleukin-18 (IL-18) into maturation whilst co-ordinately triggers caspase-6 which is responsible for apoptosis and axonal degeneration. In addition, caspase-1 activation induces pyroptosis, an inflammatory form of programmed cell death. Studies in murine AD models indicate that the Nlrp1 inflammasome is indeed upregulated in AD and neuronal death is observed leading to cognitive decline. However, the mechanism of NLRP1 inflammasome activation in AD is particularly elusive, given its structural and functional complexities. In this review, we examine the implications of the human NLRP1 inflammasome and its signalling pathways in driving neuroinflammation in AD.

Matched MeSH terms: Neurons/pathology
Fulltext Recurrent Bell's palsy in a young woman

Ngow HA, Wan Khairina WM, Hamidon BB

Singapore Med J, 2008 Oct;49(10):e278-80.
PMID: 18946598

Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.

Matched MeSH terms: Motor Neurons/pathology
Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury

Pati S, Muthuraju S, Hadi RA, Huat TJ, Singh S, Maletic-Savatic M, et al.

Curr Stem Cell Res Ther, 2016;11(2):149-57.
PMID: 26763886

Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications.

Matched MeSH terms: Neurons/pathology*
Effect of normabaric hyperoxia treatment on neuronal damage following fluid percussion injury in the striatum of mice: a morphological approach

Muthuraju S, Pati S, Rafiqul M, Abdullah JM, Jaafar H

J Biosci, 2013 Mar;38(1):93-103.
PMID: 23385817

Traumatic brain injury (TBI) causes significant mortality in most developing countries worldwide. At present, it is imperative to identify a treatment to address the devastating post-TBI consequences. Therefore, the present study has been performed to assess the specific effect of immediate exposure to normabaric hyperoxia (NBO) after fluid percussion injury (FPI) in the striatum of mice. To execute FPI, mice were anesthetised and sorted into (i) a TBI group, (ii) a sham group without injury and (iii) a TBI group treated with immediate exposure to NBO for 3 h. Afterwards, brains were harvested for morphological assessment. The results revealed no changes in morphological and neuronal damage in the sham group as compared to the TBI group. Conversely, the TBI group showed severe morphological changes as well as neuronal damage as compared to the TBI group exposed to NBO for 3 h. Interestingly, our findings also suggested that NBO treatment could diminish the neuronal damage in the striatum of mice after FPI. Neuronal damage was evaluated at different points of injury and the neighbouring areas using morphology, neuronal apoptotic cell death and pan-neuronal markers to determine the complete neuronal structure. In conclusion, immediate exposure to NBO following FPI could be a potential therapeutic approach to reduce neuronal damage in the TBI model.

Matched MeSH terms: Neurons/pathology
Human tuberculosis brain promotes neuronal apoptosis but not in astrocytes with high expression of vascular endothelial growth factor

Othman FN, Muthuraju S, Noor SSM, Abdullah S, Mohd Yusoff AA, Tharakan J, et al.

Tuberculosis (Edinb), 2018 09;112:45-51.
PMID: 30205968 DOI: 10.1016/j.tube.2018.07.007

The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (p = 0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (p 

Matched MeSH terms: Neurons/pathology
Fulltext New clinical sign of cervical myelopathy: Wazir hand myelopathy sign

Wazir NN, Kareem BA

Singapore Med J, 2011 Jan;52(1):47-9.
PMID: 21298241

Cervical spondylotic myelopathy (CSM) represents a spectrum of pathologies with progressive compression of the spinal cord. The clinical signs and symptoms play a key role in diagnosis. The characteristic hand myelopathy signs are of significant clinical importance. The aim of this descriptive study was to report a relatively easy to elicit new hand myelopathy sign. The basis for this is finger and wrist flexor disinhibition, which is used for the spinal specificity of cord compression at or above the C5/6 level.

Matched MeSH terms: Motor Neurons/pathology
Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death

Leong YQ, Ng KY, Chye SM, Ling APK, Koh RY

Metab Brain Dis, 2020 01;35(1):11-30.
PMID: 31811496 DOI: 10.1007/s11011-019-00516-y

Extracellular senile plaques and intracellular neurofibrillary tangles are the neuropathological findings of the Alzheimer's disease (AD). Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years. However, the recent therapeutics have yet to reverse or halt this disease. Previous evidence demonstrates that the accumulation of Aβ peptides and APP can exert neurotoxicity and ultimately neuronal cell death. Hence, we discuss the mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death. Conversely, the activation of such pathways could also result in the abnormal generation of APP and Aβ peptides. An elucidation of actions of APP and its metabolite, Aβ, could be vital in suggesting novel therapeutic opportunities.

Matched MeSH terms: Neurons/pathology
Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum

Haleagrahara N, Siew CJ, Mitra NK, Kumari M

Neurosci Lett, 2011 Aug 15;500(2):139-43.
PMID: 21704673 DOI: 10.1016/j.neulet.2011.06.021

An increasing large body of research on Parkinson's disease (PD) has focused on the understanding of the mechanisms behind the potential neuro protection offered by antioxidants and iron chelating agents. In this study, the protective effect of the bioflavonoid quercetin on 6-hydroxydopamine (6-OHDA)-induced model of PD was investigated. PD was induced by a single intracisternal injection of 6-hydroxydopamine (300μg) to male Sprague-Dawley rats. Quercetin treatment (30mg/kg body weight) over 14 consecutive days markedly increased the striatal dopamine and antioxidant enzyme levels compared with similar measurements in the group treated with 6-OHDA alone. There was a significant decrease in protein carbonyl content in the striatum compared with that of rats that did not receive quercetin. A significant increase in neuronal survivability was also found with quercetin treatment in rats administered 6-OHDA. In conclusion, treatment with quercetin defended against the oxidative stress in the striatum and reduced the dopaminergic neuronal loss in the rat model of PD.

Matched MeSH terms: Neurons/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: Neurons/pathology

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