Experimental Neurology最新文献

{"title":"Circulating exosomes in pediatric obstructive sleep apnea with or without neurocognitive deficits and their effects on a 3D-blood-brain barrier spheroid model","authors":"Trupti Joshi ,&nbsp;Yen On Chan ,&nbsp;Zhuanhong Qiao ,&nbsp;Leila Kheirandish-Gozal ,&nbsp;David Gozal ,&nbsp;Abdelnaby Khalyfa","doi":"10.1016/j.expneurol.2025.115188","DOIUrl":"10.1016/j.expneurol.2025.115188","url":null,"abstract":"<div><div>Obstructive sleep apnea (OSA) in children is linked to cognitive impairments, potentially due to blood-brain barrier (BBB) dysfunction. Exosomes, small vesicles released by most cells, reflect cellular changes. This study examined the effects of exosomes from children with OSA, with or without cognitive deficits, on neurovascular unit (NVU) models. Twenty-six children were categorized into three groups: healthy controls (Cont, <em>n</em> = 6), OSA without cognitive deficits (OSA-NG, <em>n</em> = 10), and OSA with neurocognitive deficits (OSA-POS, n = 10). Plasma exosomes were characterized and applied to human 3D NVU spheroids for 24 h. Barrier integrity, permeability, and angiogenesis were assessed using trans-endothelial electrical resistance (TEER), tight junction integrity, and tube formation assays. Single-nucleus RNA sequencing (snRNA-seq) and bioinformatics, including CellChat analysis, identified intercellular signaling pathways. Results showed that exosomes from OSA-POS children disrupted TEER, increased permeability, and impaired ZO1 staining in spheroids, compared to the other groups. Both OSA-POS and OSA-NG exosomes increased permeability in NVU cells in monolayer and microfluidic BBB models. snRNA-seq analysis further revealed distinct cell clusters and pathways associated with the different groups. This 3D NVU spheroid model provides a robust platform to study BBB properties and the role of exosomes in OSA. These findings suggest that integrating snRNA-seq with exosome studies can uncover mechanisms underlying neurocognitive dysfunction in pediatric OSA, potentially leading to personalized therapeutic approaches.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115188"},"PeriodicalIF":4.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476158","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":"Neuronal mechanisms underlying activation of locomotor network by epidural electrical stimulation of the spinal cord","authors":"Pavel E. Musienko ,&nbsp;Pavel V. Zelenin ,&nbsp;Vladimir F. Lyalka ,&nbsp;Polina Yu. Shkorbatova ,&nbsp;Oleg V. Gorskii ,&nbsp;Tatiana G. Deliagina","doi":"10.1016/j.expneurol.2025.115187","DOIUrl":"10.1016/j.expneurol.2025.115187","url":null,"abstract":"<div><div>Epidural electrical stimulation of the spinal cord (ES) is used to restore/improve locomotor movements in patients. However, the neuronal mechanisms underlying activation of locomotor networks by ES are unknown. Here, we analyzed the effects of ES on the activity of individual spinal neurons of different functional locomotor groups. Neuronal activity was recorded in decerebrate cats before and during ES that evoked locomotion. During ES initial period (NW-period, before the locomotion onset), the activity was increased in most neurons as compared to that before ES. We found that ES-caused activation of neurons of locomotor network to the average level similar to that observed during locomotion is not sufficient for initiation of locomotion. We demonstrated that the onset of ES-evoked locomotion was associated with specific changes in the activity of individual neurons within functional locomotor groups and in their responses to epidural stimuli. With the locomotion onset, there was a trend for individual neurons with extremely high activity during NW-period to decrease their activity, while for neurons with extremely low activity to become more active. Also, in neurons contributing to generation of a specific mode of locomotion, peaks and troughs in responses to individual epidural stimuli were significantly less pronounced as compared with those observed during NW-period. We suggest that these changes allow ES to maintain the high level of excitability of the locomotor network necessary for its operation without distortion of the locomotor rhythm. The obtained results advance our understanding of the neuronal mechanisms underlying activation of locomotor network by ES.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115187"},"PeriodicalIF":4.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463647","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":"Tg-SwDI transgenic mice: A suitable model for Alzheimer's disease and cerebral amyloid angiopathy basic research and preclinical studies","authors":"Adrian Rodriguez-Lopez ,&nbsp;Daniel Esteban ,&nbsp;Allan Noé Domínguez-Romero ,&nbsp;Goar Gevorkian","doi":"10.1016/j.expneurol.2025.115189","DOIUrl":"10.1016/j.expneurol.2025.115189","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is the most common neurodegenerative disease and the most frequent cause of dementia. Characteristic features observed in the brain of AD patients are the accumulation of amyloid beta peptide (Aβ) aggregates, neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein, neuronal and synaptic loss, and elevated levels of oxidative stress and inflammatory markers. Cerebral amyloid angiopathy (CAA) is another common cause of cognitive decline characterized by the accumulation of Aβ in the cerebral vasculature. The precise overlapping pathogenic mechanisms underlying the co-occurrence of AD and CAA are not very well understood. However, vascular dysfunction observed at early stages is considered a key phenomenon. Tg-SwDI transgenic mice expressing human Aβ precursor protein (AβPP) harboring the Swedish K670N/M671L and vasculotropic Dutch/Iowa E693Q/D694N mutations in the brain have been extensively used to study many pathological features observed in AD/CAA patients and to design biomarkers and therapeutic strategies. The present review summarizes studies addressing different features mimicking human disease in Tg-SwDI mice: parenchymal and cerebral vascular amyloid accumulation, neuroinflammation, complement overactivation, cerebrovascular, mitochondrial and GABAergic system dysfunction, altered NO synthesis, circadian rhythm disruptions, lead exposure effect, among others. Also, reports that evaluated anti-Aβ and anti-inflammatory strategies and compounds capable of delaying or reversing vascular dysfunction and the impairment of GABAergic transmission in Tg-SwDI mice are analyzed. This review may help researchers determine this model's appropriateness for future studies of a particular mechanism or a novel treatment protocol.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115189"},"PeriodicalIF":4.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454404","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":"Long-term variable photoperiod exposure impairs hippocampal synapse involving of the glutamate system and leads to memory deficits in male Wistar rats","authors":"Yuanyuan Hou ,&nbsp;Yao Zuo ,&nbsp;Shaofei Song ,&nbsp;Tong Zhang","doi":"10.1016/j.expneurol.2025.115191","DOIUrl":"10.1016/j.expneurol.2025.115191","url":null,"abstract":"<div><div>Excessive artificial light at night can induce the human circadian misalignment, potentially impairing memory consolidation and the rhythms of hippocampal clock genes. To investigate the impact of circadian misalignment on hippocampal function, we measured various field excitatory postsynaptic potentials (fEPSP) and golgi staining in the CA1 and dentate gyrus (DG) regions in Wistar rats. Our findings revealed that circadian misalignment resulted in a leftward shift in the input-output (I-O) curve within the CA1 region, decreased long-term potentiation (LTP), multi-time interval paired-pulse ratio (PPR), as well as dendritic spines and complexity across both CA1 and DG regions. Additionally, magnetic resonance spectroscopy (MRS) showed that circadian misalignment downregulated glutamate-related neurotransmitters (Glu + Gln) in the hippocampus, contributing to impaired synaptic function. Furthermore, disruptions to glutamate receptor subunits due to circadian misalignment led to reduced expression of AMPA receptor and NMDA receptor subunits in the hippocampus. In summary, our results suggest that memory impairments resulting from circadian misalignment are associated with diminished functionality within the glutamatergic system; this includes reductions in both Glx levels and availability of glutamate receptor subunits—key factors contributing to compromised synaptic function within the hippocampus.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115191"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457367","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":"Differential effects of sound repetition rate on auditory cortex development and behavior in fragile X syndrome mouse model","authors":"A.O. Norman ,&nbsp;N. Farooq ,&nbsp;A. Sahni ,&nbsp;K. Tapia ,&nbsp;D. Breiner ,&nbsp;K.A. Razak ,&nbsp;I.M. Ethell","doi":"10.1016/j.expneurol.2025.115184","DOIUrl":"10.1016/j.expneurol.2025.115184","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Fragile X syndrome (FXS) is a leading genetic form of autism and intellectual disability that is associated with a loss-of-function mutation in the &lt;em&gt;Fragile X messenger ribonucleoprotein 1&lt;/em&gt; (&lt;em&gt;Fmr1)&lt;/em&gt; gene. The &lt;em&gt;Fmr1&lt;/em&gt; knockout (KO) mouse model displays many aspects of FXS-related phenotypes and is used to study FXS pathophysiology. Sensory manipulations, such as sound exposure, are considered as a non-invasive approach to alleviate FXS phenotypes. However, it is unclear what specific sound attributes may have beneficial effects.&lt;/div&gt;&lt;div&gt;In this study, we examined the effects of sound repetition rate on auditory cortex development and FXS-associated behaviors in a mouse model of FXS. KO and wild-type (WT) male littermates were exposed to 14 kHz pure tone trains with 1 Hz or 5 Hz repetition rates during postnatal day (P)9-P21 developmental period. We analyzed the effects of developmental sound exposure on PV cell development, cortical activity and exploratory behaviors in sound-exposed WT and KO mice. We found that parvalbumin (PV) cell density was lower in the auditory cortex (AuC) of KO compared to WT mice raised in sound-attenuated environment, but was increased following the exposure to both 1 Hz and 5 Hz sound trains. However, PV protein levels were upregulated only in AuC of 5 Hz rate exposed KO mice. Interestingly, analysis of baseline cortical activity using electroencephalography (EEG) recordings showed that sound attenuation or exposure to sound trains with 5 Hz, but not 1 Hz, repetition rates corrected enhanced resting state gamma power in AuC of KO mice to WT levels. In addition, sound attenuation and exposure to 5 Hz showed some beneficial effects on the synchronization to frequency-modulated chirp in the frontal cortex (FC) of both WT and KO mice. Analysis of event-related potentials (ERP) in response to broadband sound showed increased ongoing responses and decreased habituation to noise stimuli in the AuC and FC of naive KO mice. While sound-attenuation and exposure to 5 Hz showed no significant effects on the power of onset and ongoing responses, exposure to 1 Hz further enhanced ongoing responses and decreased habituation to sound in both WT and KO mice. Finally, developmental exposure to sound trains with 5 Hz, but not 1 Hz, repetition rates normalized exploratory behaviors and improved social novelty preference but not hyperactivity in KO mice.&lt;/div&gt;&lt;div&gt;Summarizing, our results show that developmental exposure of mice to sound trains with 5 Hz, but not 1 Hz, repetition rate had beneficial effects on PV cell development, overall cortical activity and behaviors in KO mice. While sound attenuation alone normalized some EEG phenotypes, it did not improve PV development or behaviors. These findings may have a significant impact on developing new approaches to alleviate FXS phenotypes and open possibilities for a combination of sound exposure with drug treatment which may offer highly novel therapeutic ","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115184"},"PeriodicalIF":4.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440413","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":"Partial microglial depletion through inhibition of colony-stimulating factor 1 receptor improves synaptic plasticity and cognitive performance in aged mice","authors":"Luisa Strackeljan ,&nbsp;David Baidoe-Ansah ,&nbsp;Hadi Mirzapourdelavar ,&nbsp;Shaobo Jia ,&nbsp;Rahul Kaushik ,&nbsp;Carla Cangalaya ,&nbsp;Alexander Dityatev","doi":"10.1016/j.expneurol.2025.115186","DOIUrl":"10.1016/j.expneurol.2025.115186","url":null,"abstract":"<div><div>Microglia depletion, followed by repopulation, improves cognitive functions in the aged mouse brain. However, even temporal ablation of microglia puts the brain at a high risk of infection. Hence, in the present work, we studied if the partial reduction of microglia with PLX3397 (pexidartinib), an inhibitor of the colony-stimulating factor 1 receptor (CSF1R), could bring similar benefits as reported for microglia ablation. Aged (two-years-old) mice were treated with PLX3397 for a total of 6 weeks, which reduced microglia numbers in the hippocampus and retrosplenial cortex (RSC) to the levels seen in young mice and resulted in layer-specific ablation in the expression of microglial complement protein C1q mediating synaptic remodeling. This treatment boosted long-term potentiation in the CA1 region and improved performance in the hippocampus-dependent novel object location recognition task. Although PLX3397 treatment did not alter the number or total intensity of <em>Wisteria floribunda</em> agglutinin-positive perineuronal nets (PNNs) in the CA1 region of the hippocampus, it changed the fine structure of PNNs. It also elevated the expression of perisynaptic proteoglycan brevican, presynaptic vGluT1 at excitatory synapses, and vGAT in inhibitory ones in the CA1 <em>stratum radiatum</em>. Thus, targeting the CSF1R may provide a safe and efficient strategy to boost synaptic and cognitive functions in the aged brain.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115186"},"PeriodicalIF":4.6,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432703","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":"Multilineage-differentiating stress-enduring cells attenuate the cognitive impairment caused by chronic cerebral hypoperfusion in rats","authors":"Naoya Iwabuchi ,&nbsp;Hiroki Uchida ,&nbsp;Takatsugu Abe ,&nbsp;Takumi Kajitani ,&nbsp;Daiki Aburakawa ,&nbsp;Ahmed Mansour ,&nbsp;Hidenori Endo ,&nbsp;Teiji Tominaga ,&nbsp;Kuniyasu Niizuma","doi":"10.1016/j.expneurol.2025.115185","DOIUrl":"10.1016/j.expneurol.2025.115185","url":null,"abstract":"<div><div>Multilineage-differentiating stress-enduring (Muse) cells are non-tumorigenic pluripotent- like stem cells that can migrate to damaged sites and contribute to tissue repair. Chronic cerebral hypoperfusion (CCH), which mimics vascular dementia, causes hippocampal neuronal degeneration and white matter (WM) damage, which lead to cognitive dysfunction. Currently, there are no effective treatments for it. We evaluated the efficiency of the human-Muse cell-based product CL2020 in treating CCH in rats. A bilateral common carotid artery occlusion was used to induce cognitive dysfunction. Six-weeks after carotid artery occlusion, CL2020 were injected intravenously. Cognitive function was assessed using a Barnes circular maze (BCM) at 3 weeks after CL2020 administration. Histological findings and western blots were assessed at 4 weeks after CL2020 administration. BCM assessment indicated recovery in cognitive function in the CL2020-treated group. Compared with the vehicle, CL2020 targeted the hippocampus, where it decreased neuronal loss and WM damage. CL2020 also promoted angiogenesis and suppressed apoptotic cell death. Western blotting of hippocampal samples revealed the downregulation of pro- apoptotic and the upregulation of anti-apoptotic proteins in the CL2020-treated group. In conclusion, intravenous administration of CL2020 improved the cognitive deficits caused by CCH, partly because of decreased hippocampal neuronal loss and WM damage, and increased angiogenesis in the hippocampus.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115185"},"PeriodicalIF":4.6,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425436","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":"Molecular and functional changes in GABAergic transmission during epileptogenesis in a rat model of post-traumatic epilepsy","authors":"Noora Puhakka ,&nbsp;Pierangelo Cifelli ,&nbsp;Gabriele Ruffolo ,&nbsp;Alessandro Gaeta ,&nbsp;Cristina Roseti ,&nbsp;Angela Di Iacovo ,&nbsp;Johanna Tiilikainen ,&nbsp;Xavier Ekolle Ndode-Ekane ,&nbsp;Anssi Lipponen ,&nbsp;Meinrad Drexel ,&nbsp;Günther Sperk ,&nbsp;Asla Pitkänen ,&nbsp;Eleonora Palma","doi":"10.1016/j.expneurol.2025.115183","DOIUrl":"10.1016/j.expneurol.2025.115183","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is one of the leading causes of structural epilepsy. Our objective was to investigate the molecular and functional dysregulation of GABAergic neurotransmission during a wide time window from acute to chronic phases of epileptogenesis after TBI. Perilesional and thalamic tissues sampled from a clinically relevant animal model of post-traumatic epilepsy induced by lateral fluid-percussion injury were investigated using <em>in situ</em> hybridization, immunohistochemistry and RNA sequencing. For functional analysis, we utilized a membrane microtransplantation technique in <em>Xenopus</em> oocytes in order to overcome the technical difficulties that would stem from recording directly from highly damaged lesional and perilesional brain tissues. Already at 6 to 24 h post-TBI we found a dysregulation in the expression of GABA_AR β3- and δ-subunits, which persisted for up to 4 months. Further, gene set enrichment analysis revealed a negative enrichment of GABA receptor signaling in the perilesional cortex and ipsilateral thalamus. These changes occurred in parallel to the dysregulation of the two main cation-chloride cotransporter genes (<em>Slc12a2</em> and <em>Slc12a5</em>) both in the perilesional cortex and the ipsilateral thalamus. Our functional analysis revealed that the GABA current reversal potential (E_GABA) was shifted towards more depolarized values in the perilesional cortex and ipsilateral thalamus. Our data demonstrate a rapid onset and long-lasting duration of GABAergic dysfunction after TBI and support the hypothesis that an early treatment with agents modulating the GABAergic transmission in the thalamo-cortical-thalamic circuitry may suppress early seizures as well as prevent or slow down epileptogenesis after TBI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"387 ","pages":"Article 115183"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406477","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":"Traumatic brain injury-induced anxiety: Injury and plasticity of the central noradrenergic system","authors":"Shigeharu Tsuda ,&nbsp;Jiamei Hou ,&nbsp;Floyd J. Thompson ,&nbsp;Prodip K. Bose","doi":"10.1016/j.expneurol.2025.115182","DOIUrl":"10.1016/j.expneurol.2025.115182","url":null,"abstract":"<div><div>Long-term anxiety is a hallmark symptom following traumatic brain injury (TBI). Although the central noradrenergic system (CNAS) is known to play a critical role in anxiety by regulating the excitability of several intricately interconnected brain structures via its projections to them, critical questions remain regarding the nature and extent of TBI-induced neuroplastic alterations in the CNAS and how these alterations relate to anxiety disorders. Knowledge relative to these questions is pivotal to development and refinement of therapies for TBI-associated anxiety disorders, including post-traumatic stress disorder. To this end, this study was designed to determine the impacts of chronic TBI on neuroplasticity of the CNAS and their significance in anxiety disorders in a clinically relevant rodent model. A standardized weight-drop model was used to produce controlled impacts of mild-to-moderate TBI in rats. Following the elevated plus maze tests to longitudinally assess anxiety-like behavior at 2 and 18 weeks post-injury of TBI animals, brain tissues of naïve and TBI rats were coronally sectioned and immunostained for a noradrenergic (NA) marker (dopamine β-hydroxylase) and neuronal nuclei in the central NA production sites and critical anxiety-regulating brain structures. We discovered that TBI caused robust losses of NA cells in the locus coeruleus and NA innervation of the central nucleus of the amygdala, an emotional processing center. Conversely, TBI caused intense gains of NA cells in the A2/A1 cell groups and NA innervation of other major anxiety-regulating regions. These changes coincided with progressively elevated anxiety-like behavior. Possibly, NA properties of A2/A1 cells were upregulated to compensate for the TBI-induced severe cell losses in the locus coeruleus. We conclude that these bi-directional vast alterations in the CNAS following chronic TBI contribute to dysregulated anxiety and, in part, the pathophysiology of human post-traumatic stress disorder.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115182"},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390538","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":"Advances in brain ischemia mechanisms and treatment approaches: Recent insights and inflammation-driven risks","authors":"Doyoon Kim ,&nbsp;Satoru Morikawa ,&nbsp;Taneaki Nakagawa ,&nbsp;Hideyuki Okano ,&nbsp;Yoshitaka Kase","doi":"10.1016/j.expneurol.2025.115177","DOIUrl":"10.1016/j.expneurol.2025.115177","url":null,"abstract":"<div><div>The application of existing radical treatments for stroke is limited to a small number of cases, with current practices predominantly focusing on conservative therapy. This review examines the pathophysiology of excitotoxicity, oxidative stress, and inflammation during brain ischemia caused by stroke, highlighting insights into each pathology and reporting the latest therapeutic developments that are expected to serve as new treatment options. Finally, we outline the recent attention given to the relationship between periodontal disease and stroke. We propose addressing the limitations of existing treatments for stroke and suggest novel therapeutic approaches while also presenting the potential contribution of periodontal disease treatment to the prevention of stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"386 ","pages":"Article 115177"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374041","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}