Experimental Neurology最新文献

{"title":"Activity-dependent extracellular potassium changes in unmyelinated versus myelinated areas in olfactory regions of the isolated female guinea-pig brain","authors":"Laura Uva ,&nbsp;Gaia Bruno ,&nbsp;Marco de Curtis","doi":"10.1016/j.expneurol.2024.114884","DOIUrl":"10.1016/j.expneurol.2024.114884","url":null,"abstract":"<div><p>The potassium released in the extracellular space during neuronal activity is rapidly removed by glia and neurons to maintain tissue homeostasis. Oligodendrocyte-derived myelin axonal coating contributes to potassium buffering and is therefore crucial to control brain excitability.</p><p>We studied activity-dependent extracellular potassium ([K⁺]_o) changes in the piriform cortex (PC), a region that features highly segregated bundles of myelinated and unmyelinated fibers. Four-aminopyridine (4AP; 50 μM) treatment or patterned high-frequency stimulations (hfST) were utilized to generate [K⁺]_o changes measured with potassium-sensitive electrodes in the myelinated lateral olfactory tract (LOT), in the unmyelinated PC layer I and in the myelinated deep PC layers in the <em>ex vivo</em> isolated guinea-pig brain.</p><p>Seizure-like events induced by 4AP are initiated by the abrupt [K⁺]_o rise in the layer I formed by unmyelinated fibers (Uva et al., 2017). Larger [K⁺]_o shifts occurred in unmyelinated layers compared to the myelinated LOT. LOT hfST that mimicks pre-seizure discharges also generated higher [K⁺]_o changes in unmyelinated PC layer I than in LOT and deep PC layers. The treatment with the Kir4.1 potassium channel blocker BaCl₂ (100 μM) enhanced the [K⁺]_o changes generated by hfST in myelinated structures.</p><p>Our data show that activity-dependent [K⁺]_o changes are intrinsically different in myelinated <em>vs</em> unmyelinated cortical regions. The larger [K⁺]_o shifts generated in unmyelinated structures may represent a vehicle for seizure generation.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LanCL1 protects developing neurons from long-term isoflurane anesthesia-induced neurotoxicity","authors":"","doi":"10.1016/j.expneurol.2024.114880","DOIUrl":"10.1016/j.expneurol.2024.114880","url":null,"abstract":"<div><p>Research has revealed that prolonged or repeated exposure to isoflurane, a common general anesthetic, can lead to cognitive and behavioral deficiencies, particularly in early life. The brain contains a wealth of LanCL1, an antioxidant enzyme that is thought to mitigate oxidative stress. Nevertheless, its precise function in mammals remains uncertain. This study uncovered a decrease in the expression of LanCL1 due to prolonged isoflurane anesthesia, accompanied by anesthesia-induced neurotoxicity in vivo and in vitro. To better understand LanCL1's essential function, LanCL1 overexpressing adenoviruses were employed to increase LanCL1 levels. The outcomes were analyzed using western blot and immunofluorescence methods. According to the findings, extended exposure to isoflurane anesthesia may lead to developmental neurotoxicity in vivo and in vitro. The anesthesia-induced neurotoxicity was concomitant with a reduction in LanCL1 expression. Moreover, the study revealed that overexpression of LanCL1 can mitigate the neurotoxic effects of isoflurane anesthesia, resulting in improved synaptic growth, less reactive oxygen species, enhanced cell viability and rescued memory deficits in the developing brain. In conclusion, prolonged anesthesia-induced LanCL1 deficiency could be responsible for neurotoxicity and subsequent cognitive impairments in the developing brain. Additional LanCL1 counteracts this neurotoxic effect and protects neurons from long-term isoflurane anesthesia.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Deletion of Chitinase-3-like 1 accelerates stroke development through enhancement of Neuroinflammation by STAT6-dependent M2 microglial inactivation in Chitinase-3-like 1 knockout mice” [Exp Neurol. 2020 Jan:323:113082]","authors":"","doi":"10.1016/j.expneurol.2024.114871","DOIUrl":"10.1016/j.expneurol.2024.114871","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624001973/pdfft?md5=f996a95c0aff302f84d6203fcc73fd61&pid=1-s2.0-S0014488624001973-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moderate intensity aerobic exercise alleviates motor deficits in 6-OHDA lesioned rats and reduces serum levels of biomarkers of Parkinson's disease severity without recovery of striatal dopamine or tyrosine hydroxylase","authors":"Ella A. Kasanga ,&nbsp;Isabel Soto ,&nbsp;Ashley Centner ,&nbsp;Robert McManus ,&nbsp;Marla K. Shifflet ,&nbsp;Walter Navarrete ,&nbsp;Yoonhee Han ,&nbsp;Jerome Lisk ,&nbsp;Travis Ehrhardt ,&nbsp;Ken Wheeler ,&nbsp;Isha Mhatre-Winters ,&nbsp;Jason R. Richardson ,&nbsp;Christopher Bishop ,&nbsp;Vicki A. Nejtek ,&nbsp;Michael F. Salvatore","doi":"10.1016/j.expneurol.2024.114875","DOIUrl":"10.1016/j.expneurol.2024.114875","url":null,"abstract":"<div><p>Alleviation of motor impairment by aerobic exercise (AE) in Parkinson's disease (PD) patients points to activation of neurobiological mechanisms that may be targetable by therapeutic approaches. However, evidence for AE-related recovery of striatal dopamine (DA) signaling or tyrosine hydroxylase (TH) loss has been inconsistent in rodent studies. This ambiguity may be related to the timing of AE intervention in relation to the status of nigrostriatal neuron loss. Here, we replicated human PD at diagnosis by establishing motor impairment with &gt;80% striatal DA and TH loss prior to initiating AE, and assessed its potential to alleviate motor decline and restore DA and TH loss. We also evaluated if serum levels of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of human PD severity, changed in response to AE. 6-hydroxydopamine (6-OHDA) was infused unilaterally into rat medial forebrain bundle to induce progressive nigrostriatal neuron loss over 28 days. Moderate intensity AE (3× per week, 40 min/session), began 8–10 days post-lesion following establishment of impaired forelimb use. Striatal tissue DA, TH protein and mRNA, and serum levels of NfL/GFAP were determined 3-wks after AE began. Despite severe striatal DA depletion at AE initiation, forelimb use deficits and hypokinesia onset were alleviated by AE, without recovery of striatal DA or TH protein loss, but reduced NfL and GFAP serum levels. This proof-of-concept study shows AE alleviates motor impairment when initiated with &gt;80% striatal DA loss without obligate recovery of striatal DA or TH protein. Moreover, the AE-related reduction of NfL and GFAP serum levels may serve as objective blood-based biomarkers of AE efficacy.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for optimal parameters for modified pharyngeal electrical stimulation for the treatment of dysphagia after stroke in rats","authors":"Jiahui Hu ,&nbsp;Qianqian Wang ,&nbsp;Yong Dai ,&nbsp;Yueqin Tian ,&nbsp;Nenggui Xu ,&nbsp;Hongmei Wen ,&nbsp;Zulin Dou ,&nbsp;Qiuping Ye","doi":"10.1016/j.expneurol.2024.114878","DOIUrl":"10.1016/j.expneurol.2024.114878","url":null,"abstract":"<div><p>Pharyngeal electrical stimulation (PES), a novel noninvasive peripheral nerve stimulation technique, can effectively improve neurogenic dysphagia and increase the safety and effectiveness of swallowing in the clinic. However, the lack of animal models for dysphagia has limited the mechanistic research on PES, which affects its wide application. Therefore, determining optimal parameters for PES in rats is needed to enable mechanistic studies. Modified PES (mPES), which has different waves and pulse widths from PES, was used; in previous studies mPES was found to have a neurological mechanism like that of PES. A poststroke dysphagia (PSD) model was established, and rats with dysphagia were grouped into three different intensities (0.1 mA, 0.5 mA, and 1 mA) for the selection of optimal intensity and three different frequencies (1 Hz, 2 Hz, and 5 Hz) for the selection of optimal frequency based on a stimulation duration of 10 min in the clinic. A Videofluroscopic Swallow Screen (VFSS) was used to assess swallowing function in rats before and after mPES treatment. The results showed that the 1 mA group had better swallowing function (<em>p &lt; 0.05</em>) than the model group. Compared with the model group, the 1 Hz and 5 Hz groups had the same improvement in swallowing function (<em>p &lt; 0.05</em>). However, the increase in excitatory signals in the sensorimotor cortex was more pronounced in the 5 Hz group than in the other frequency stimulation groups (<em>p &lt; 0.05</em>). Combining the clinical findings with the above results, we concluded that the optimal stimulation parameter for mPES in rats is “frequency: 5 Hz, current intensity: 1 mA for 10 min/day”, which provides a basis for future basic experimental studies of mPES in animals.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624002048/pdfft?md5=4647f90a3161928e5cd535077ca292d4&pid=1-s2.0-S0014488624002048-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Fluoxetine ameliorates behavioral and neuropathological deficits in a transgenic model mouse of α-synucleinopathy” Exp Neurol. 2012 April; 234(2): 405–416","authors":"","doi":"10.1016/j.expneurol.2024.114873","DOIUrl":"10.1016/j.expneurol.2024.114873","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624001997/pdfft?md5=f039fe9764933d649e76f57e1a51debb&pid=1-s2.0-S0014488624001997-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmenting fibronectin levels in injured adult CNS promotes axon regeneration in vivo","authors":"Agnieszka Lukomska ,&nbsp;Bruce A. Rheaume ,&nbsp;Matthew P. Frost ,&nbsp;William C. Theune,&nbsp;Jian Xing,&nbsp;Ashiti Damania,&nbsp;Ephraim F. Trakhtenberg","doi":"10.1016/j.expneurol.2024.114877","DOIUrl":"10.1016/j.expneurol.2024.114877","url":null,"abstract":"<div><p>In an attempt to repair injured central nervous system (CNS) nerves/tracts, immune cells are recruited into the injury site, but endogenous response in adult mammals is insufficient for promoting regeneration of severed axons. Here, we found that a portion of retinal ganglion cell (RGC) CNS projection neurons that survive after optic nerve crush (ONC) injury are enriched for and upregulate fibronectin (Fn)-interacting integrins Itga5 and ItgaV, and that Fn promotes long-term survival and long-distance axon regeneration of a portion of axotomized adult RGCs in culture. We then show that, Fn is developmentally downregulated in the axonal tracts of optic nerve and spinal cord, but injury-activated macrophages/microglia upregulate Fn while axon regeneration-promoting zymosan augments their recruitment (and thereby increases Fn levels) in the injured optic nerve. Finally, we found that Fn's RGD motif, established to interact with Itga5 and ItgaV, promotes long-term survival and long-distance axon regeneration of adult RGCs after ONC <em>in vivo</em>, with some axons reaching the optic chiasm when co-treated with Rpl7a gene therapy. Thus, experimentally augmenting Fn levels in the injured CNS is a promising approach for therapeutic neuroprotection and axon regeneration of at least a portion of neurons.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing cognitive recovery in chronic traumatic brain injury through simultaneous allosteric modulation of α7 nicotinic acetylcholine and α5 GABAA receptors","authors":"Alyssa F. Balleste ,&nbsp;Akhila Sangadi ,&nbsp;David J. Titus ,&nbsp;Timothy Johnstone ,&nbsp;Derk Hogenkamp ,&nbsp;Kelvin W. Gee ,&nbsp;Coleen M. Atkins","doi":"10.1016/j.expneurol.2024.114879","DOIUrl":"10.1016/j.expneurol.2024.114879","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective therapeutic strategies to ameliorate these chronic learning and memory impairments after TBI are limited. Two pharmacological targets for enhancing cognition are nicotinic acetylcholine receptors (nAChRs) and GABA_A receptors (GABA_ARs), both of which regulate hippocampal network activity to form declarative memories. A promising compound, 522–054, both allosterically enhances α7 nAChRs and inhibits α5 subunit-containing GABA_ARs. Administration of 522–054 enhances long-term potentiation (LTP) and cognitive functioning in non-injured animals. In this study, we assessed the effects of 522–054 on hippocampal synaptic plasticity and learning and memory deficits in the chronic post-TBI recovery period. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 12 wk after injury, we assessed basal synaptic transmission and LTP at the Schaffer collateral-CA1 synapse of the hippocampus. Bath application of 522–054 to hippocampal slices reduced deficits in basal synaptic transmission and recovered TBI-induced impairments in LTP. Moreover, treatment of animals with 522–054 at 12 wk post-TBI improved cue and contextual fear memory and water maze acquisition and retention without a measurable effect on cortical or hippocampal atrophy. These results suggest that dual allosteric modulation of α7 nAChR and α5 GABA_AR signaling may be a potential therapy for treating cognitive deficits during chronic recovery from TBI.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen mitigates brain injury by prompting NEDD4-CX43- mediated mitophagy in traumatic brain injury","authors":"Fan Wu ,&nbsp;Tao Liang ,&nbsp;Yang Liu ,&nbsp;Yongxing Sun ,&nbsp;Baoguo Wang","doi":"10.1016/j.expneurol.2024.114876","DOIUrl":"10.1016/j.expneurol.2024.114876","url":null,"abstract":"<div><h3>Background</h3><p>Hydrogen (H₂) has emerged as a potential therapeutic intervention for traumatic brain injury (TBI). However, the precise mechanism underlying H₂'s neuroprotective effects in TBI remain incompletely understood.</p></div><div><h3>Methods</h3><p>TBI mouse model was induced using the controlled cortical impact (CCI) method, and a cell model was established by exposing astrocytes to lipopolysaccharide (LPS). Cell viability was detected by CCK-8 kits. Cell apoptosis was measured by flow cytometry. ELISA was used to detect cytokine quantification. Protein and gene expression was detected by western blot and RT-PCR analysis. Co-immunoprecipitation (CO-IP) were employed for protein-protein interactions. Morris water maze test and rotarod test were applied for TBI mice.</p></div><div><h3>Results</h3><p>H₂ treatment effectively inhibited the LPS-induced cell injury and cell apoptosis in astrocytes. NEDD4 expression was increased following H₂ treatment coupled with enhanced mitophagy in LPS-treated astrocytes. Overexpression of NEDD4 and down-regulation of connexin 43 (CX43) mirrored the protective effects of H₂ treatment in LPS-exposed astrocytes. NEDD4 interacts CX43 to regulates the ubiquitinated degradation of CX43. While overexpression of CX43 reversed the protective effects of H₂ treatment in LPS-exposed astrocytes. In addition, H₂ treatment significantly alleviated brain injury in TBI mouse model.</p></div><div><h3>Conclusion</h3><p>H₂ promoted NEDD4-CX43 mediated mitophagy to protect brain injury induced by TBI, highlighting a novel pathway underlying the therapeutic effects of H₂ in TBI.</p></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Neurogenesis changes and the fate of progenitor cells after subarachnoid hemorrhage in rats” [Experimental Neurology 311 (2019) 274–284]","authors":"","doi":"10.1016/j.expneurol.2024.114872","DOIUrl":"10.1016/j.expneurol.2024.114872","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014488624001985/pdfft?md5=3c226f3ef8bc1e5ee486dfcc58340060&pid=1-s2.0-S0014488624001985-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}