Neuroscience Applied最新文献

{"title":"A single subanaesthetic dose of the rapid-acting antidepressant S-ketamine raises presynaptic SV2A density in limbic regions of the Wistar Kyoto rat model of depression","authors":"Simone Larsen Bærentzen,&nbsp;Anna Lee Waszkiewicz,&nbsp;Majken Thomsen,&nbsp;Celine Knudsen,&nbsp;Betina Elfving,&nbsp;Anne M. Landau","doi":"10.1016/j.nsa.2024.104079","DOIUrl":"https://doi.org/10.1016/j.nsa.2024.104079","url":null,"abstract":"<div><p>The N-methyl-D-aspartate receptor (NMDA-R) antagonist S-ketamine has been approved as a rapid-acting antidepressant for treatment-resistant depression (TRD). The antidepressant mechanisms have not fully been elucidated; however, alterations of synaptic proteins and mechanisms may play a vital role. Here, we study the effect of a single subanaesthetic dose of 15 mg/kg S-ketamine vs saline 1 h after administration in the Wistar Kyoto rat model of depression on the density of synaptic vesicle glycoprotein 2A (SV2A) and the metabotropic glutamate receptor 5 (mGluR5) using [³H]UCB-J and [³H]MPEPγ autoradiography, respectively, compared with control Wistar Hannover rats. In a separate cohort of Wistar Kyoto rats, we investigate the transcriptional regulation of presynaptic markers <em>Sv2a, Syn 1–3, Syt 1–3, Synaptophysin</em>, <em>Vamp1, 2, 5, and 7</em>, postsynaptic markers <em>Homer1-3, Nrg 1, Nlgn 2, Nlgn 3, Psd95</em>, NMDA receptor subunits <em>Nr2a, Nr2b</em>, AMPA receptor subunits <em>Gria1-3</em>, GABA type A receptor-associated protein (<em>Gabarap</em>), glutamate metabotropic receptor subtype 5 (<em>Grm5</em>), and brain-derived neurotrophic factor (<em>Bdnf</em>) using real-time quantitative polymerase chain reaction (qPCR) in hippocampus in response to S-ketamine vs saline injection. In Wistar Kyoto rats, S-ketamine increases [³H]UCB-J binding to SV2A compared to saline-injected controls in the nucleus accumbens and dorsal and ventral hippocampus, an effect absent in the Wistar Hannover strain. No changes were observed in [³H]MPEPγ binding to mGluR5, nor in gene regulation. S-ketamine can regulate presynaptic SV2A density in brain areas relevant to depression in the Wistar Kyoto model, but not in controls, suggesting a role for SV2A in the antidepressant effects of S-ketamine.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104079"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524001443/pdfft?md5=38be6cfa7e52dae610a4d2153a548671&pid=1-s2.0-S2772408524001443-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verbal memory performance in adolescents and adults with ADHD","authors":"A.D. Pawley ,&nbsp;J.S. Mayer ,&nbsp;J. Medda ,&nbsp;G.A. Brandt ,&nbsp;J.C. Agnew-Blais ,&nbsp;P. Asherson ,&nbsp;A.-S. Rommel ,&nbsp;J.A. Ramos-Quiroga ,&nbsp;J. Palacio Sanchez ,&nbsp;D. Bergsma ,&nbsp;J.K. Buitelaar ,&nbsp;F.B. Ortega ,&nbsp;A. Muntaner-Mas ,&nbsp;O. Grimm ,&nbsp;A. Reif ,&nbsp;C.M. Freitag ,&nbsp;J. Kuntsi","doi":"10.1016/j.nsa.2024.103941","DOIUrl":"10.1016/j.nsa.2024.103941","url":null,"abstract":"<div><p>Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD.</p><p>We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed.</p><p>ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables.</p><p>Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 103941"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524000061/pdfft?md5=ba7d07e8020ddee85583f610ada796c9&pid=1-s2.0-S2772408524000061-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139637311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"measuring plasticity to predict the likelihood of recovery from major depression","authors":"M. Mobasher ,&nbsp;I. Branchi ,&nbsp;C. Delli Colli ,&nbsp;F. Chiarotti ,&nbsp;A. Giuliani","doi":"10.1016/j.nsa.2024.103997","DOIUrl":"https://doi.org/10.1016/j.nsa.2024.103997","url":null,"abstract":"","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 103997"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524000620/pdfft?md5=172d38f84b2459bfbd35fc00721109b4&pid=1-s2.0-S2772408524000620-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subjective fatigue in individuals with anxiety and mood disorders correlates with specific traits of obsessive-compulsive personality disorder","authors":"Agne Stanyte ,&nbsp;Naomi A. Fineberg ,&nbsp;Aurelija Podlipskyte ,&nbsp;Julija Gecaite-Stonciene ,&nbsp;Julius Burkauskas","doi":"10.1016/j.nsa.2024.104048","DOIUrl":"10.1016/j.nsa.2024.104048","url":null,"abstract":"<div><p>Fatigue is a common debilitating symptom in individuals with anxiety and mood disorders, also known as common mental disorders (CMD). Aspects of fatigue are seen to be independently associated with the presence of obsessive-compulsive personality disorder (OCPD) in individuals with CMD. However, the relationship between different traits of OCPD and fatigue is still under-researched. Therefore, the aim of our study was to examine the associations between individual OCPD traits and fatigue in those with CMD. This cross-sectional study investigated 203 individuals (76.8% female, mean age 40.8 ± 11.8) attending a stress-related disorders day care unit. Participants were evaluated for OCPD traits by using the Compulsive Personality Assessment Scale and completed the Multidimensional Fatigue Inventory-20. Out of 203 participants, 42 (20.7%) fulfilled operational criteria for OCPD (73.8% female). Participants with OCPD had greater reduced motivation, mental and physical fatigue scores than those without OCPD (13.2 ± 3.6 vs. 14.5 ± 3.6, p = 0.035; 14.4 ± 4.3 vs. 16.1 ± 3.5, p = 0.023; 13.5 ± 4.3 vs. 15.0 ± 4.3, p = 0.049, respectively). In individuals with OCPD, higher levels of rigidity correlated with physical fatigue (ρ = 0.463, p = 0.002) and reduced activity (ρ = 0.363, p = 0.018), while preoccupation with details was associated with reduced motivation (ρ = 0.437, p = 0.004). In conclusion, in individuals with CMD and comorbid OCPD, several OCPD traits were significantly related to subjective measures of fatigue. As traits are considered stable features, there results suggest they might play a causative role in generating subjective fatigue in CMD.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104048"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524001133/pdfft?md5=98fbf43004103a07e1230ddda041fb91&pid=1-s2.0-S2772408524001133-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139882301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network analysis on Homer1a-expression in schizophrenia animal model and synaptic modulation by dopamine D2R antagonist","authors":"B. Mazza ,&nbsp;L. Vellucci ,&nbsp;A. Barone ,&nbsp;E.F. Buonaguro ,&nbsp;M. Ciccarelli ,&nbsp;G. De Simone ,&nbsp;F. Marmo ,&nbsp;C. Tomasetti ,&nbsp;F. Iasevoli ,&nbsp;A. De Bartolomeis","doi":"10.1016/j.nsa.2024.104026","DOIUrl":"https://doi.org/10.1016/j.nsa.2024.104026","url":null,"abstract":"","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104026"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524000917/pdfft?md5=bb08cf5aaad7b3b81c953a6556838fe4&pid=1-s2.0-S2772408524000917-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacotherapy in obsessive compulsive disorder: a meta-analysis and meta-regression of placebo-controlled trials","authors":"S. Cohen ,&nbsp;J. Zantvoord ,&nbsp;B. Storosum ,&nbsp;T. Mattila ,&nbsp;J. Daams ,&nbsp;B. Wezenberg ,&nbsp;A. De Boer ,&nbsp;D. Denys","doi":"10.1016/j.nsa.2024.103964","DOIUrl":"https://doi.org/10.1016/j.nsa.2024.103964","url":null,"abstract":"","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 103964"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524000292/pdfft?md5=c6ebe5112648c2891f6bfd9807dee62c&pid=1-s2.0-S2772408524000292-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation in comorbid depression in Alzheimer's disease: A pilot study using post-mortem brain tissue","authors":"Jordan T. Lin ,&nbsp;Mizuki Morisaki ,&nbsp;Srisharnitha A. Sampathkumar ,&nbsp;Laurie C. Lau ,&nbsp;Delphine Boche ,&nbsp;Golam M. Khandaker ,&nbsp;Lindsey I. Sinclair","doi":"10.1016/j.nsa.2024.104051","DOIUrl":"10.1016/j.nsa.2024.104051","url":null,"abstract":"<div><p>Comorbid depression and Alzheimer's disease (AD) is associated with poorer prognosis than either condition alone. Neuroinflammation has been implicated in the pathogenesis and progression of both depression and AD, but much of the existing research has been based on peripheral blood immune markers. Relatively little is known about the neuroinflammatory environment when these conditions occur simultaneously and using immune measures directly in the brain tissue. This pilot study aimed to examine brain inflammatory marker changes in AD cases comparing those with and without comorbid depression.</p><p>Post-mortem brain tissue from AD cases with depression (n = 23) and AD cases with no history of psychiatric illness (n = 25) were analyzed for a range of inflammatory markers, including markers of microglial function (Iba1, P2RY12, CD64 and CD68 measured by immunohistochemistry); endothelial inflammatory markers (ICAM-1 and VCAM-1 measured by ELISA); and cytokine levels (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α measured using Mesoscale Discovery Multiplex Assays).</p><p>Brains of AD cases with comorbid depression, compared with AD alone, had increased IL-4 in the superior frontal gyrus and increased TNFα &amp; IL-12p70 in the insula. Levels of all other inflammatory markers including markers of microglial function and endothelial inflammation were similar between the two groups.</p><p>We found no consistent changes in cytokines between the two brain regions in individuals with comorbid depression in AD. Further work in larger cohorts is needed to understand brain region specificity of immune marker alterations and the relationship of these changes with pre-mortem clinical outcomes.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104051"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524001169/pdfft?md5=181de25a9584c1ea819137ead5df6f44&pid=1-s2.0-S2772408524001169-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colour vision impairments in bipolar disorder: A systematic review","authors":"Jason Tran ,&nbsp;Arnav Gupta ,&nbsp;Nicholas Fabiano ,&nbsp;Vinita Dhir ,&nbsp;Katherine Larose ,&nbsp;Iris Lasker ,&nbsp;Stanley Wong ,&nbsp;Ibrahim Y.Z. Mohammad ,&nbsp;Steven Le ,&nbsp;Jess G. Fiedorowicz ,&nbsp;Risa Shorr ,&nbsp;Andrea Zampieri ,&nbsp;Alessio Bellato ,&nbsp;Samuele Cortese ,&nbsp;Marco Solmi","doi":"10.1016/j.nsa.2024.104057","DOIUrl":"10.1016/j.nsa.2024.104057","url":null,"abstract":"<div><p>Visual impairments are common in patients with bipolar disorder (BD), and the neuropathophysiology may suggest a potential influence on colour vision. This systematic review aimed to assess existing data of colour vision impairment, including chromatic discrimination and colour blindness in patients with BD. Comprehensive literature search compliant with PRISMA 2020 was conducted in Medline, Embase, and Google Scholar from inception to February 28th, 2023. Our inclusion criteria were: (1) patients with a diagnosis of bipolar I or II disorder based on DSM, ICD, or clinical diagnosis, and (2) study investigating colour vision (i.e., including colour blindness and discrimination), with (3) no restrictions on the condition of the comparator group. Study quality appraisal was performed using the NIH Study Quality Assessment Tool. Five studies from Brazil, Netherlands, and USA, with 338 patients were included. Three cross-sectional studies assessed chromatic discrimination and two case-series assessed colour blindness in patients with BD. The three cross-sectional studies support reduced chromatic discrimination during mild to moderate mania in BD when compared to healthy comparators. The latter two articles presented low evidence of an X-linked inheritance of BD. Our review indicates evidence of reduced chromatic discrimination in mild to moderate mania. However, further research is needed to validate these findings and to extend to other mood states in BD given current limitations. Future studies can benefit from further multi-institutional data, larger sample sizes, appropriate blinding, the use of biomarkers, and statistical adjustment to confounders to fully elucidate the role of chromatic discrimination in BD.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104057"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524001224/pdfft?md5=8a56ac6cb53f7a84d23224c57df6b12e&pid=1-s2.0-S2772408524001224-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140283208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A machine learning pipeline for efficient differentiation between bipolar and major depressive disorder based on multimodal structural neuroimaging","authors":"Federico Calesella ,&nbsp;Federica Colombo ,&nbsp;Beatrice Bravi ,&nbsp;Lidia Fortaner-Uyà ,&nbsp;Camilla Monopoli ,&nbsp;Sara Poletti ,&nbsp;Emma Tassi ,&nbsp;Eleonora Maggioni ,&nbsp;Paolo Brambilla ,&nbsp;Cristina Colombo ,&nbsp;Irene Bollettini ,&nbsp;Francesco Benedetti ,&nbsp;Benedetta Vai","doi":"10.1016/j.nsa.2023.103931","DOIUrl":"10.1016/j.nsa.2023.103931","url":null,"abstract":"<div><p>Due to the overlapping depressive symptomatology with major depressive disorder (MDD), 60% of patients with bipolar disorder (BD) are initially misdiagnosed, calling for the definition of reliable biomarkers that can support the diagnostic process. Here, we optimized a machine learning pipeline for the differentiation between depressed BD and MDD patients based on multimodal structural neuroimaging features. Diffusion tensor imaging (DTI) and T1-weighted magnetic resonance imaging (MRI) data were acquired for 282 depressed BD (n = 180) and MDD (n = 102) patients. Images were preprocessed to obtain axial (AD), radial (RD), mean (MD) diffusivity, fractional anisotropy (FA), and voxel-based morphometry (VBM) maps. Each feature was entered separately into a 5-fold nested cross-validated predictive pipeline differentiating between BD and MDD patients, comprising: confound regression for nuisance variables removal, feature standardization, principal component analysis for feature reduction, and an elastic-net penalized regression. The DTI-based models reached accuracies ranging from 75% to 78%, whereas the VBM model reached 61% of accuracy. All the models were significantly different from a null model distribution at a 5000-permutation test. A 5000 bootstrap procedure revealed that widespread differences drove the classification, with BD patients associated to overall higher values of AD and FA, and grey matter volumes. Our results suggest that structural neuroimaging, in particular white matter microstructure and grey matter volumes, may be able to differentiate between MDD and BD patients with good predictive accuracy, being significantly higher than chance-level.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 103931"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408523029137/pdfft?md5=4ae53c21a2570d689b748b56bb864848&pid=1-s2.0-S2772408523029137-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139024196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nose to brain delivery of flurbiprofen from a solid lipid nanoparticles-based thermosensitive in-situ gel.","authors":"Ashok J. Choudhary,&nbsp;Sakshi S. Mahajan,&nbsp;Anuradha S. Majumdar","doi":"10.1016/j.nsa.2024.104062","DOIUrl":"https://doi.org/10.1016/j.nsa.2024.104062","url":null,"abstract":"<div><p>Flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), has selective amyloid-lowering characteristics and can be utilized for Alzheimer's disease treatment. Oral flurbiprofen has poor brain bioavailability and high dose-related gastrointestinal adverse effects. To overcome these issues, the study aimed to formulate intranasal flurbiprofen solid lipid nanoparticles (SLN) based thermosensitive <em>in-situ</em> gel. SLN were formulated by the High-speed homogenization method. A 2³ factorial design technique was utilized for optimization, wherein the influence of two independent variables, critical process parameters (X₁ = surfactant concentration, X₂ = D:L ratio) on critical quality attributes (Y₁ = particle size, Y₂=Percent Drug Loading, Y₃=Percent Entrapment Efficiency) was ascertained at three distinct levels. The optimized SLN were then prepared into an SLN-based intranasal thermosensitive <em>in-situ</em> gel with Poloxamer 188 P (1.2% w/v) and Poloxamer 407 P (18% w/v). The <em>in-vitro</em> flurbiprofen release study demonstrated a 100% release of flurbiprofen from the SLN-based thermosensitive <em>in-situ</em> gel at 6 h. The <em>ex-vivo</em> flurbiprofen release study revealed a complete release of flurbiprofen from the SLN-based thermosensitive <em>in-situ</em> gel at 8 h. In the <em>in-vivo</em> tests, the <em>in-situ</em> gel (2 mg/kg) administered intranasally in rats demonstrated nearly three times greater brain bioavailability (C_max = 490.3 ng/ml) than the oral marketed formulation of flurbiprofen, Ansaid® (10 mg/kg) (C_max = 145.1 ng/ml). The plasma concentration obtained with intranasal <em>in-situ</em> gel (C_max = 2.5 μg/ml) was lower than the oral marketed formulation (C_max = 3.4 μg/ml). The time necessary to establish the maximal flurbiprofen concentration (T_max) in the brain was 2 and 0.5 h for oral and intranasal formulations, respectively. Hence, the intranasal formulation could achieve maximal drug concentration in the brain in less time. Thus, flurbiprofen SLN-based thermosensitive <em>in-situ</em> gel can be a potential encouraging safe, non-invasive, and efficacious replacement to oral formulations for achieving direct brain targeting through nose-to-brain drug delivery, thereby treating neuroinflammatory conditions like Alzheimer's disease.</p></div>","PeriodicalId":100952,"journal":{"name":"Neuroscience Applied","volume":"3 ","pages":"Article 104062"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772408524001273/pdfft?md5=44c56390985a14af37a9af479da27b33&pid=1-s2.0-S2772408524001273-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}