Neurotoxicity Research最新文献

{"title":"Restoration of MPTP-induced Dopamine and Tyrosine Hydroxylase Depletion in the Mouse Brain Through Ethanol and Nicotine.","authors":"Mostofa Jamal, Sella Takei, Ikuko Tsukamoto, Takanori Miki, Ken-Ichi Ohta, Md Zakir Hossain, Hiroshi Kinoshita","doi":"10.1007/s12640-025-00732-8","DOIUrl":"10.1007/s12640-025-00732-8","url":null,"abstract":"<p><p>Dopamine (DA) has long been considered a major factor in the development of Parkinson's disease (PD). Ethanol (EtOH) and nicotine (Nic), either alone or in combination, have been shown to affect nigrostriatal dopaminergic neuronal activity. Here, we investigate whether EtOH and Nic alone or in co-exposure can restore the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine (DA), DA metabolites, and tyrosine hydroxylase (TH) in the striatum and hippocampus of C57BL/6N mice. MPTP-treated mice were treated intraperitoneally with saline (control), EtOH (1.0-3.0 g/kg), Nic (0.5-2.0 mg/kg), or a combination of EtOH and Nic. Brain samples were collected 1 h after treatment. DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA) were measured by HPLC-ECD, while TH protein content and TH phosphorylation at Ser31 (pSer31 TH) were quantified by Western blot. EtOH (2.0 and 3.0 g/kg) alone reversed the effects of MPTP treatment in both studied brain regions, as evidenced by an increase in DA, DOPAC, and HVA contents, TH protein, and pSer31 TH compared to the MPTP group, indicating restorative effects on DA neurons in the MPTP model. Likewise, Nic (1.0 and 2.0 mg/kg) alone reversed MPTP treatment effects, with treated mice showing increased DA, DOPAC, and HVA contents, TH protein, and pSer31 TH compared to MPTP mice. Co-administration of EtOH (2.0 g/kg) and Nic (1.0 mg/kg) further increased DA, DOPAC and HVA tissue contents, TH protein, and pSer31 TH, indicating an additive effect. These results show that moderate to high doses of EtOH and Nic induce similar increases in brain DA and TH via TH phosphorylation activation in MPTP model mice. EtOH and Nic showed an additive effect in combination, suggesting that their co-application could be a potent therapeutic strategy for treating PD.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"9"},"PeriodicalIF":2.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol-Induced Autophagy Ameliorates Tau Protein Clearance.","authors":"Talita A M Vrechi, Gabriel C Guarache, Rafaela Brito Oliveira, Erika da Cruz Guedes, Adolfo G Erustes, Anderson H F F Leão, Vanessa C Abílio, Antonio W Zuardi, Jaime Eduardo C Hallak, José Alexandre Crippa, Claudia Bincoletto, Rodrigo P Ureshino, Soraya S Smaili, Gustavo J S Pereira","doi":"10.1007/s12640-025-00729-3","DOIUrl":"10.1007/s12640-025-00729-3","url":null,"abstract":"<p><p>Tau is a neuronal protein that confers stability to microtubules; however, its hyperphosphorylation and accumulation can lead to an impairment of protein degradation pathways, such as autophagy. Autophagy is a lysosomal catabolic process responsible for degrading cytosolic components, being essential for cellular homeostasis and survival. In this context, autophagy modulation has been postulated as a possible therapeutic target for the treatment of neurodegenerative diseases. Studies point to the modulatory and neuroprotective role of the cannabinoid system in neurodegenerative models and here it was investigated the effects of cannabidiol (CBD) on autophagy in a human neuroblastoma strain (SH-SY5Y) that overexpresses the EGFP-Tau WT (Wild Type) protein in an inducible Tet-On system way. The results demonstrated that CBD (100 nM and 10 µM) decreased the expression of AT8 and total tau proteins, activating autophagy, evidenced by increased expression of light chain 3-II (LC3-II) protein and formation of autophagosomes. Furthermore, the cannabinoid compounds CBD, ACEA (CB1 agonist) and GW-405,833 (CB2 agonist) decreased the fluorescence intensity of EGFP-Tau WT; and when chloroquine, an autophagic blocker, was used, there was a reversal in the fluorescence intensity of EGFP-Tau WT with CBD (1 and 10 µM) and GW-405,833 (2 µM), demonstrating the possible participation of autophagy in these groups. Thus, it was possible to conclude that CBD induced autophagy in EGFP-Tau WT cells which increased tau degradation, showing its possible neuroprotective role. Hence, this study may contribute to a better understanding of how cannabinoids can modulate autophagy and present a potential therapeutic target in a neurodegeneration model.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"8"},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glioprotective Effects of Resveratrol Against Glutamate-Induced Cellular Dysfunction: The Role of Heme Oxygenase 1 Pathway.","authors":"André Quincozes-Santos, Larissa Daniele Bobermin, Ana Carolina Tramontina, Krista Minéia Wartchow, Vanessa-Fernanda Da Silva, Vitor Gayger-Dias, Natalie K Thomaz, Aline Daniel Moreira de Moraes, Daniele Schauren, Patrícia Nardin, Carmem Gottfried, Diogo Onofre Souza, Carlos-Alberto Gonçalves","doi":"10.1007/s12640-025-00730-w","DOIUrl":"10.1007/s12640-025-00730-w","url":null,"abstract":"<p><p>Resveratrol, a natural polyphenol, has shown promising neuroprotective effects in several in vivo and in vitro experimental models. However, the mechanisms by which resveratrol mediates these effects are not fully understood. Glutamate is the major excitatory neurotransmitter in the brain; however, excessive extracellular glutamate levels can affect neural activity in several neurological diseases. Astrocytes are the glial cells that maintain brain homeostasis and can attenuate excitotoxicity by actively participating in glutamate neurotransmission. This study aimed to investigate the glioprotective effects of resveratrol against glutamate-induced cellular dysfunction in hippocampal slices and primary astrocyte cultures, with a focus on the role of heme-oxygenase 1 (HO-1). Glutamate impaired glutamate uptake activity through a glutamate receptor-dependent mechanism, in addition to altering other important astroglial parameters, including glutamine synthetase activity, glutathione levels and cystine uptake, which were normalized by resveratrol. Resveratrol also prevented glutamate-induced disruption in antioxidant defenses, as well as in trophic and inflammatory functions, including the nuclear factor κB (NFκB) transcriptional activity. Most of the effects of resveratrol, mainly in astrocytes, were dependent on the HO-1 signaling pathway, as they were abrogated when HO-1 was pharmacologically inhibited. Resveratrol also increased HO-1 mRNA expression and its transcriptional regulator, nuclear factor erythroid-derived 2-like 2 (Nrf2). Finally, resveratrol prevented glutamate-induced p21 senescence marker, indicating an anti-aging effect. Therefore, we demonstrated that the activation of the Nrf2/HO-1 system in astrocytes by resveratrol represents an astrocyte-targeted neuroprotective mechanism in neurodegeneration, with glutamate excitotoxicity, oxidative stress, and neuroinflammation as common neurochemical alterations.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"7"},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Dexmedetomidine Promoted HSPB8 Expression via Inhibiting the lncRNA SNHG14/UPF1 Axis to Inhibit Apoptosis of Nerve Cells in AD : The Role of Dexmedetomidine in AD.","authors":"QingYun Tan, LiLi Liu, Shuo Wang, QingDong Wang, Yu Sun","doi":"10.1007/s12640-025-00728-4","DOIUrl":"10.1007/s12640-025-00728-4","url":null,"abstract":"","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"6"},"PeriodicalIF":2.9,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Different Impacts of Ketamine on Neurotrophic Factors and Inflammatory Parameters in a Cecal Ligation and Puncture-Induced Sepsis Model.","authors":"Jorge M Aguiar-Geraldo, Lara Canever, Debora P Marino, Camila Coan, Taise Possamai-Della, Bruna Pescador, João Quevedo, Felipe Dal-Pizzol, Samira S Valvassori, Alexandra Ioppi Zugno","doi":"10.1007/s12640-024-00727-x","DOIUrl":"10.1007/s12640-024-00727-x","url":null,"abstract":"<p><p>Given ketamine's conflicting impacts on the central nervous system, investigating its effects within an inflammatory context becomes crucial. This study aimed to assess the impact of varying ketamine doses on neurotrophin and inflammatory cytokine levels within the brains of rats submitted to the sepsis model. Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis. Intraperitoneal ketamine injections (5, 15, or 25 mg/kg) or saline were administered daily for seven days, thirty days post-CLP. Rats were euthanized thirty minutes following the last injection for analysis of IL-1β, IL-6, IL-10, TNF-α, BDNF, NGF, NT-3, and GDNF levels in the frontal cortex, hippocampus, and striatum. CLP-induced elevated IL-1𝛽, IL-6, IL-10, and TNF-α levels in the frontal cortex and hippocampus of rats, with reduced BDNF levels across all structures examined. Furthermore, reduced NGF and GDNF levels were observed solely in the hippocampus. Ketamine at 5 mg/kg normalized CLP-induced alterations and, in Sham animals, increased BDNF and NGF levels in the frontal cortex and/or hippocampus. At 15 mg/kg, ketamine elevated BDNF and NGF levels in Sham animals, while at 25 mg/kg, it exacerbated the inflammatory response initiated by CLP. These findings suggest variable effects of ketamine within a context of systemic inflammation, emphasizing the importance of considering individual inflammatory backgrounds when utilizing ketamine.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"5"},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.","authors":"Masato Asanuma, Ikuko Miyazaki, Jean Lud Cadet","doi":"10.1007/s12640-024-00725-z","DOIUrl":"10.1007/s12640-024-00725-z","url":null,"abstract":"<p><p>To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration. The knockdown of Ndfip1 expression with Ndfip1 siRNA significantly aggravated METH-induced neurotoxicity in the cultured monoaminergic neuronal cells. These results suggest that drastic increases in Ndfip1 mRNA is compensatory reaction to protect neurons against METH-induced neurotoxicity.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"4"},"PeriodicalIF":2.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Improves Hippocampal Cell Bioenergetics, Redox and Inflammatory Markers, and Synaptic Proteins, Regulating Mitochondrial Calcium Homeostasis.","authors":"Claudia Jara, Angie K Torres, Han S Park-Kang, Lisette Sandoval, Claudio Retamal, Alfonso Gonzalez, Micaela Ricca, Sebastián Valenzuela, Michael P Murphy, Nibaldo C Inestrosa, Cheril Tapia-Rojas","doi":"10.1007/s12640-024-00726-y","DOIUrl":"10.1007/s12640-024-00726-y","url":null,"abstract":"<p><p>Mitochondria produces energy through oxidative phosphorylation (OXPHOS), maintaining calcium homeostasis, survival/death cell signaling mechanisms, and redox balance. These mitochondrial functions are especially critical for neurons. The hippocampus is crucial for memory formation in the brain, which is a process with high mitochondrial function demand. Loss of hippocampal function in aging is related to neuronal damage, where mitochondrial impairment is critical. Synaptic and mitochondrial dysfunction are early events in aging; both are regulated reciprocally and contribute to age-associated memory loss together. We previously showed that prolonged treatment with Curcumin or Mitoquinone (MitoQ) improves mitochondrial functions in aged mice, exerting similar neuroprotective effects. Curcumin has been described as an anti-inflammatory and antioxidant compound, and MitoQ is a potent antioxidant directly targeting mitochondria; however, whether Curcumin exerts a direct impact on the mitochondria is unclear. In this work, we study whether Curcumin could have a mechanism similar to MitoQ targeting the mitochondria. We utilized hippocampal slices of 4-6-month-old C57BL6 mice to assess the cellular changes induced by acute Curcumin treatment ex-vivo compared to MitoQ. Our results strongly suggest that both compounds improve the synaptic structure, oxidative state, and energy production in the hippocampus. Nevertheless, Curcumin and MitoQ modify mitochondrial function differently; MitoQ improves the mitochondrial bioenergetics state, reducing ROS production and increasing ATP generation. In contrast, Curcumin reduces mitochondrial calcium levels and prevents calcium overload related to mitochondrial swelling. Thus, Curcumin is described as a new regulator of mitochondrial calcium homeostasis and could be used in pathological events involving calcium deregulation and excitotoxicity, such as aging and neurodegenerative diseases.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabigerol Mitigates Haloperidol-Induced Vacuous Chewing Movements in Mice.","authors":"R Ponciano, J E C Hallak, J A Crippa, F S Guimarães, Elaine Ap Del Bel","doi":"10.1007/s12640-024-00724-0","DOIUrl":"10.1007/s12640-024-00724-0","url":null,"abstract":"<p><p>Chronic use of typical antipsychotics can lead to varying motor effects depending on the timing of analysis. Acute treatment typically induces hypokinesia, resembling parkinsonism, while repeated use can result in tardive dyskinesia, a hyperkinetic syndrome marked by involuntary orofacial movements, such as vacuous chewing movements in mice. Tardive dyskinesia is particularly concerning due to its potential irreversibility and associated motor discomfort. One prevailing theory suggests that tardive dyskinesia arises from hypersensitivity of D2-type dopaminergic receptors caused by continuous blockade from typical antipsychotics like haloperidol. Additionally, increased inflammation, oxidative stress, and elevated FosB protein expression in the dorsolateral striatum are implicated in its pathophysiology. Current treatments for tardive dyskinesia often lack clear efficacy and may lead to significant side effects. Cannabigerol, a non-psychotomimetic cannabinoid with antioxidant and anti-inflammatory properties, has been investigated for its potential antidyskinetic effects. In this study, mice were treated with cannabigerol at doses of 3 and 10 mg/kg to evaluate its ability to prevent, ameliorate, or reverse haloperidol-induced vacuous chewing movements. Cannabigerol successfully reduced vacuous chewing movements without affecting normal motor activity, exacerbating haloperidol-induced hypokinesia, or inducing dyskinetic effects on its own. However, no significant reversal of the haloperidol-induced motor effects was observed under the current protocol. Furthermore, cannabigerol did not alter FosB expression or microglia morphology. These findings underscore the need for further research to explore cannabigerol's therapeutic potential and contribute to our understanding of its possible clinical applications in managing tardive dyskinesia.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"2"},"PeriodicalIF":2.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of Pyrethroid Neurotoxicity for Human Health: A Lesson from Animal Models.","authors":"Mega Obukohwo Oyovwi, Adedeji David Atere, Paul Chimwuba, Uchechukwu Gregory Joseph","doi":"10.1007/s12640-024-00723-1","DOIUrl":"10.1007/s12640-024-00723-1","url":null,"abstract":"<p><p>Pyrethroids, synthetic insecticides used in pest management, pose health risks, particularly neurotoxic effects, with studies linking exposure to a neurodegenerative disorder. This review examines the neurotoxic mechanisms of pyrethroids analyzing literature from animal model studies. It identifies critical targets for neurotoxicity, including ion channels, oxidative stress, inflammation, neuronal cell loss, and mitochondrial dysfunction. The review also discusses key therapeutic targets and signaling pathways relevant to Pyrethroids neurotoxicity management, including calcium, Wnt/β-catenin, mTOR, MAPK/Erk, PI3K/Akt, Nrf2, Nurr1, and PPARγ. Our findings demonstrate that pyrethroid exposure triggers multiple neurotoxic pathways that bear resemblance to the mechanisms underlying neurotoxicity. Oxidative stress and inflammation emerge as prominent factors that contribute to neuronal degeneration, alongside disrupted mitochondrial function. The investigation highlights the significance of ion channels as primary neurodegeneration targets while acknowledging the potential involvement of various other receptors and enzymes that may exacerbate neurological damage. Additionally, we elucidate how pyrethroids may interfere with therapeutic targets associated with neuronal dysfunction, potentially impairing treatment efficacy.Also, exposure to these chemicals can alter DNA methylation patterns and histone modifications, ultimately leading to changes in gene expression that may enhance susceptibility to neurological disorders. Pyrethroid neurotoxicity poses a significant public health risk, necessitating future research for protective strategies against pesticide-induced neurological disorders and understanding the interplay between neurodegenerative diseases, potentially leading to innovative therapeutic interventions.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"43 1","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Benefit of 3% Hypertonic Saline Following Experimental Intracerebral Hemorrhage.","authors":"Tiffany F C Kung, Anna C J Kalisvaart, Angely Claire C Suerte, Glen C Jickling, Frank K H van Landeghem, Frederick Colbourne","doi":"10.1007/s12640-024-00722-2","DOIUrl":"10.1007/s12640-024-00722-2","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is a stroke subtype with a high mortality rate (~ 40%). After ICH, the mass effect of the hematoma and edema contribute to raised intracranial pressure (ICP) and poor outcome. Endogenous compensatory mechanisms that blunt ICP elevations include redirection of venous blood and cerebrospinal fluid, along with brain tissue compliance (e.g., decreased cell volume, increased cell density); however, these limited reserves can be exhausted after severe stroke, resulting in decompensated ICP that requires careful clinical management. Management strategies can include administration of hypertonic saline (HTS), an osmotic agent that putatively attenuates edema, and thereby ICP elevations. Evidence regarding the efficacy of HTS treatment following ICH remains limited. In this study, adult male rats were given a collagenase-induced striatal ICH and a bolus of either 3% HTS or 0.9% saline vehicle at 2- and 14-hours post-stroke onset. Neurological deficits, edema, ipsilateral cell volume and density (in areas S1 and CA1), and contralateral CA1 ultrastructural morphology were assessed 24 h post-ICH. Animals had large bleeds (median 108.2 µL), extensive edema (median 83.9% brain water content in ipsilateral striatum), and evident behavioural deficits (median 5.4 neurological deficit scale score). However, HTS did not affect edema (p ≥ 0.4797), behaviour (p = 0.6479), cell volume (p ≥ 0.1079), or cell density (p ≥ 0.0983). Qualitative ultrastructural assessment of contralateral area CA1 suggested that HTS administration was associated with paradoxical cellular swelling in ICH animals. Overall, there was no benefit with administering 3% HTS after ICH.</p>","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"42 6","pages":"44"},"PeriodicalIF":2.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}