International Journal of Neuroscience

Costa, Aldo F.; Martínez A., Paula; Peláez V., Nazaret; Peral Q., Alejandro; Estévez, José C.

doi: 10.1080/00207454.2021.1990915pmid: 34623197

Abstract Objective Sphenoid sinuses mucocele (SSM) is an uncommon cause of orbital apex syndrome (OAS). Diagnosis of neurological complications in SSM might be delayed when the expansion of mucocele beyond the sinuses is not evident in conventional sinuses imaging. Methods We present a case of a 76-years old man with spared-pupil ophthalmoplegia associated with ptosis caused by a unilateral left SSM in which internal carotid artery Doppler ultrasound showed distal sub-occlusion waves pattern. Results Sinus occupation was noted in the magnetic resonance imaging (MRI) and was further evaluated in computed tomography (CT) scan and MR angiography. Nor CT or MR angiography showed clear evidence of neighboring structures compression. Doppler ultrasound of internal carotid showed high-resistance waveforms and decreased wave velocities helping diagnosis. Structures compression was confirmed intra-operatively and the patient was discharged asymptomatic after sphenoid sinus drainage. Conclusion In this first report of carotid Doppler ultrasound findings in a patient with a neurological presentation of a sphenoid sinus mucocele, a high-resistance waveform of the internal carotid may help differentiate uncomplicated sinusitis from invasive mucocele.

Mohamad Najib, Nor Haliza; Yahaya, Mohamad Fairuz; Das, Srijit; Teoh, Seong Lin

doi: 10.1080/00207454.2021.1990916pmid: 34623211

Abstract Introduction Parkinson’s disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish. Methodology A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis. Results qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment. Conclusion Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

Kaiserova, Michaela; Kastelikova, Anetta; Grambalova, Zuzana; Otruba, Pavel; Zapletalova, Jana; Mensikova, Katerina; Rosales, Raymond; Kanovsky, Petr

doi: 10.1080/00207454.2021.1991922pmid: 34666599

Abstract Background The pathophysiology of abnormal temperature sensation in Parkinson’s disease (PD) remains unclear. Abnormal thermal detection does not seem to depend on the dopaminergic deficit, suggesting that other systems play a role in these changes, probably both central and peripheral. Methods We measured thermal detection thresholds (TDT) using quantitative sensory testing (QST) in 28 patients with PD and compared them with 15 healthy controls. Results Of 28 patients, 21% had increased TDT according to the normative data. TDT were higher on the dominant side. No correlation between TDT and disease duration, severity of motor impairment, and dopaminergic therapy was observed. 50% of the patients had difficulty differentiating between warm and cold stimuli, as TDT were within the normal range in most of these patients. Conclusions Twenty-one percent of the patients in our study had increased TDT according to the normative data. Abnormal thermal detection was more pronounced on the dominant side. Abnormal differentiation between the thermal stimuli suggest impaired central processing of thermal information.

Liu, Gaoxin; Rong, Xiaoming; Lin, Xinrou; Wang, Hongxuan; He, Lei; Peng, Ying

doi: 10.1080/00207454.2021.1993848pmid: 35353669

Abstract Background and purpose: Glioma is a frequent primary brain tumor. MicroRNAs (miRNA) have been shown to potentially play a crucial part in tumor development. Based on miRNAs and clinical factors, a model was constructed to predict the glioma prognosis. Methods: The miRNA expression profiles of glioma come from The Cancer Genome Atlas (TCGA, training group) and Chinese Glioma Genome Atlas (CGGA, validation group). Regression analyses of Cox and Lasso were applied to identity miRNAs associated with glioma prognosis in the TCGA database. The miRNAs were combined with clinical factors to construct individualized prognostic prediction models, whose performance was validated in the CGGA database. The role of miRNA in glioma development was investigated by in vitro experiments. Results: We identified five key miRNAs associated with glioma prognosis and constructed a prediction model. The area under ROC curve for predicting 3-year survival of glioma patients in the TCGA and CGGA groups was 0.844 and 0.770, respectively. The nomogram constructed using the miRNA risk scores and clinical factors showed high accuracy of prediction in the TCGA group (C-index of 0.820) and the CGGA group (C-index of 0.722). The miR-196b-5p altered the migration, proliferation, invasion, and apoptosis of glioma cells by regulating target genes, according to in vitro experiments. Conclusions: A miRNA-based individualized prognostic prediction model was constructed for glioma and miR-196b-5p was identified as a potential biomarker of glioma development.

Wataya, Takafumi; Takasaki, Sakura; Hoshino, Misuzu; Makioka, Haruki; Nakamura, Genshu; Matsuda, Naoto

doi: 10.1080/00207454.2021.1995382pmid: 34809526

Abstract Purpose Nusinersen is the first disease-modifying therapy to treat spinal muscular atrophy (SMA). This report describes the safety and effectiveness of nusinersen in Japanese clinical use using two data sources: an ongoing Japanese post-marketing surveillance (PMS) and the safety database of the marketing authorisation holder, Biogen . Materials and Methods The PMS is evaluating the safety and effectiveness of nusinersen in all patients treated with nusinersen in Japan between August 2017 and August 2025; this interim analysis included data up to May 30, 2019. Biogen safety database data up to June 30, 2019 were also included to capture adverse events (AEs) from after the interim analysis cutoff date. Collected data included medical history, dosage and administration, and AEs. Safety assessment included AEs and serious AEs (SAEs). Effectiveness analyses included motor function assessments and clinical global impressions of improvement. Results Of 271 patients in the PMS population, 94 had SMA type I (34.7%), and 177 had SMA types II–IV (65.3%). AEs occurred in 67 patients (24.7%) and SAEs in 23 patients (8.5%). The Biogen safety database contained reports of 345 AEs; the most common were pneumonia, headache, and pyrexia, consistent with symptoms of SMA and lumbar puncture. In the analysis set, 26.2% of patients receiving nusinersen showed motor function improvements and 99.6–100.0% showed overall improvement. Conclusion In this interim analysis of the PMS and Biogen safety database, nusinersen had a favourable benefit–risk profile in Japanese patients with SMA.

Campbell, Renee; Chabot, Isabelle; Rousseau, Ben; Bridge, Daisy; Nicol, Gillian; Meier, Genevieve

doi: 10.1080/00207454.2021.1995383pmid: 34668828

Abstract Study objective The objective of this study was to define and characterize the unmet needs in the pharmacological management of insomnia. Methods A systematic literature review was conducted to identify relevant literature reporting real-world evidence in insomnia, published from January 2009 to April 2020. Pharmacological treatments – both prescription (benzodiazepines, ‘Z-drugs’ and suvorexant) and off-label (antidepressants, antipsychotics, and antihistamines) – were considered. Results Overall, 108 publications describing the humanistic (n = 59) and economic burden (n = 20) of insomnia, off-label treatment patterns (n = 28) and factors influencing treatment adherence or persistence (n = 8) were identified. A high prevalence of comorbid conditions was reported in patients with insomnia resulting in significantly lower health-related QoL compared to those with insomnia or a comorbidity alone. Current treatment options were associated with adverse events, including reduced sleep quality and next-day somnolence. An increased risk of accidents/injuries was also associated with insomnia and its treatment. Furthermore, safety concerns and perceived lack of efficacy for approved treatments have led to frequent off-label prescribing, despite a lack of clinical evidence of risk/benefit ratios. Safety concerns associated with benzodiazepines include risk of dependence, leading to prolonged treatment persistence and exacerbated adverse events, making them unsuitable for use in patients with chronic insomnia. Finally, the substantial economic burden of insomnia was evident, with reduced work productivity demonstrated in patients with insomnia compared to the general population. Conclusions This review highlights a clear unmet need for insomnia therapies that improve sleep quality without resulting in next-day impairment and/or dependence.

Sobhanifar, Mohammad-Ali; Rashidi, Roghayeh; Rajabian, Arezoo; Forouzanfar, Fatemeh; Hasanpour, Maede; Iranshahi, Mehrdad; Rakhshandeh, Hassan; Hosseini, Azar

doi: 10.1080/00207454.2021.1998045pmid: 35213269

Abstract Background Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. Methods The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. Results The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. Conclusion This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Wu, Gui-Mei; Du, Cai-Ping; Xu, Yan

doi: 10.1080/00207454.2021.2010732pmid: 34818135

Abstract Purpose Although amyloid-β (Aβ) is one of the neuropathological hallmarks of Alzheimer’s Disease (AD), the mechanisms of Aβ neurotoxicity remain to be clarified. This study was aimed to evaluate the effect of Aβ on postsynaptic density-95 (PSD-95) tyrosine phosphorylation. Elucidating the regulatory mechanisms underlying it may be a promising therapy in AD. Methods Aβ25–35 oligomers (20 μg/rat) were administered intracerebroventricularly in adult male Sprague-Dawley rats. PSD-95 tyrosine phosphorylation was assessed using immunoprecipitation followed by immunoblot analysis. Immunoblot was applied for measuring the protein levels of PSD-95 and β-actin. Results Following 3, 7, 14, 21 days after oligomeric Aβ25–35 treatment, the tyrosine phosphorylation of PSD-95 increased significantly, and peaked at 3 days after oligomeric Aβ25–35 treatment in hippocampal CA1 subfield. Src family protein tyrosine kinases (SrcPTKs) specific inhibitor PP2 attenuated the tyrosine phosphorylation of PSD-95 induced by Aβ25–35. Amantadine [N-methyl-D-aspartate (NMDA) receptor noncompetitive antagonist], NVP-AAM077 (GluN2A-containing NMDA receptor selective inhibitor) and Ro25-6981 (GluN2B-containing NMDA receptor selective inhibitor) also suppressed the Aβ25–35-induced PSD-95 tyrosine phosphorylation. Conclusion These results suggest that Aβ oligomers induce the tyrosine phosphorylation of PSD-95 by SrcPTKs, which is mediated by the activation of GluN2A- and GluN2B-containing NMDA receptors.

Algahtani, Hussein; Absi, Ahmed; Shirah, Bader; Al-Maghraby, Hatim; Algarni, Hussam

doi: 10.1080/00207454.2021.2012470pmid: 34846223

Abstract Iron is an essential element for brain cells that is required for the transport of oxygen, energy generation, myelin synthesis, and production of neurotransmitters. Disturbances in the homeostatic mechanisms of iron metabolism may cause iron accumulation with subsequent oxidative stress and cellular damage. It is important to consider the possibility of both a genetic and acquired iron overload syndrome in patients with neurological symptoms and hyperferritinemia. In this article, we are reporting a unique case characterized by hyperferritinemia with widespread deposition of iron in more than one bodily organ, movement disorder, and hidden malignancy. We stress on the importance of early diagnosis using a systematic approach since early treatment with iron chelators is warranted to prevent the progression of neurological symptoms. Even those patients who have no neurological symptoms with high iron should be monitored closely and treated early to avoid the deposition of iron in the brain. Whether brain damage and MRI changes are reversible completely or partially is a subject for further research.

Elnahry, Ayman G.; Asal, Zainab B.; Shaikh, Noreen; Dennett, Kate; Abd Elmohsen, Mai N.; Elnahry, Gehad A.; Shehab, Azza; Vytopil, Michal; Ghaffari, Leila; Athappilly, Geetha K.; Ramsey, David J.

doi: 10.1080/00207454.2021.2015348