Experimental Neurology最新文献

{"title":"Corrigendum to \"Secukinumab attenuates neuroinflammation and neurobehavior defect via PKCβ/ERK/NF-κB pathway in a rat model of GMH\" [Exp Neurol. 2023 Feb; 360:114276].","authors":"Shengpeng Liu, Shuixiang Deng, Yan Ding, Jerry J Flores, Xiaoli Zhang, Xiaojing Jia, Xiao Hu, Jun Peng, Gang Zuo, John H Zhang, Ye Gong, Jiping Tang","doi":"10.1016/j.expneurol.2026.115797","DOIUrl":"https://doi.org/10.1016/j.expneurol.2026.115797","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115797"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812911","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":"Initiation site of experimentally-evoked spreading depolarizations influence tissue outcomes in a murine stroke model","authors":"Michael C. Bennett ,&nbsp;Russell A. Morton ,&nbsp;Andrew P. Carlson ,&nbsp;C. William Shuttleworth","doi":"10.1016/j.expneurol.2026.115671","DOIUrl":"10.1016/j.expneurol.2026.115671","url":null,"abstract":"<div><div>Spreading depolarization waves (SDs) are implicated in secondary expansion of brain injuries and are the target for initial clinical intervention trials. However, the assumption that SD directly causes neuronal injury has been challenged by recent findings with experimentally-induced SD in stroke models. The current study addressed this controversy by examining whether stroke consequences are confounded by the precise location of experimental SD initiation. Focal ischemic lesions were generated by transient distal middle cerebral artery occlusion in male mice. Clusters of SDs (6 at 10-min intervals) were induced by either focal KCl application or optogenetic stimulation during occlusion. SDs were initiated either in regions close to the infarct core (penumbral-SD; &lt;50% perfusion) or in less compromised tissue in the same hemisphere (remote-SD; &gt;70% perfusion). Despite the fact that all SDs fully invaded stroke expansion areas, the location of experimental SD induction had significant effects on stroke outcomes measured 48 h after reperfusion. Penumbral-SDs resulted in larger infarct expansion than seen in control stroke mice lacking experimentally-imposed SD. Conversely, remote-SDs led to significantly smaller infarcts than stroke alone. Laser speckle contrast imaging of blood flow in injury expansion areas showed enhanced hypoperfusion responses after penumbral-SDs and larger hyperemic responses after remote-SDs, suggesting that differential vascular responses could contribute to stroke outcomes. Overall, this study helps to reconcile different prior reports by showing that experimentally-induced SDs can either exacerbate or reduce stroke-induced injury depending on the SD initiation site and further strengthens evidence for injurious roles of SDs initiating in vulnerable brain tissue.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115671"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076269","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":"Imipramine improves motor impairments in a rat model of Parkinson's disease induced by 6-hydroxydopamine; the role of oxidative stress and neurotrophic factors","authors":"Mahdi Hajibabaei ,&nbsp;Bagher Jafarvand ,&nbsp;Elmira Beirami ,&nbsp;Neda Valian","doi":"10.1016/j.expneurol.2026.115646","DOIUrl":"10.1016/j.expneurol.2026.115646","url":null,"abstract":"<div><h3>Introduction</h3><div>Parkinson's disease (PD) is a progressive neurological disorder characterized by the loss of dopaminergic neurons in the substantia nigra and is associated with neuroinflammation, apoptosis, oxidative stress, and motor impairment. Imipramine, a tricyclic antidepressant, has a wide range of biological effects such as anti-inflammatory, anti-apoptotic, and free radical scavenging activities. The present study was designed to investigate the neuroprotective effect of imipramine in a rat model of PD induced by 6-hydroxydopamine (6-OHDA).</div></div><div><h3>Methods</h3><div>Male Wistar rats were treated with daily intraperitoneal administration of imipramine (20 mg/kg, for 14 days) starting 72 h after 6-OHDA injection (20 μg/rat; 4 μl in the right medial forebrain bundle (MFB)). The motor performance was assessed using the rotarod, beam, pole, and apomorphine-induced rotation tests. The protein levels of neurotrophic factors (BDNF, GDNF, and NT3) and factors involved in oxidative stress (MDA, CAT, SOD, GST, and GSH) were measured in the striatum by ELISA technique. The neuronal survival was also evaluated by Nissl staining.</div></div><div><h3>Results</h3><div>Our results showed that 6-OHDA caused motor impairments and neuronal cell death. It also significantly reduced the protein levels of neurotrophic factors and induced an oxidative stress response in the striatum of rats. Whereas, imipramine treatment effectively reduced 6-OHDA-induced motor deficits and neuronal cell death. This improvement was accompanied by an increase in neurotrophic factors, especially GDNF, as well as a reduction in oxidative stress through increased SOD levels.</div></div><div><h3>Conclusion</h3><div>These findings provide direct evidence that imipramine treatment contributes to improve of neuronal cell death and motor deficits, perhaps by increasing the striatal levels of SOD and GDNF, which play a key role in the survival of dopaminergic neurons. Further studies are also needed to elucidate the precise underlying molecular mechanisms of neuroprotective effects of imipramine.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115646"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988894","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":"Mismatch between oxygen delivery and consumption in the cerebral watershed during subacute global hypoperfusion","authors":"Baoqiang Li ,&nbsp;Hewei Cao ,&nbsp;Hajime Takase ,&nbsp;Srinivasa Rao Allu ,&nbsp;Yimeng Wu ,&nbsp;Buyin Fu ,&nbsp;Sergei A. Vinogradov ,&nbsp;Eng H. Lo ,&nbsp;Ken Arai ,&nbsp;Cenk Ayata ,&nbsp;Sava Sakadžić","doi":"10.1016/j.expneurol.2026.115666","DOIUrl":"10.1016/j.expneurol.2026.115666","url":null,"abstract":"<div><div>Hemodynamically significant carotid artery stenosis is a common clinical condition that can lead to chronic cerebral hypoperfusion. Despite the well-recognized pivotal role of pial collaterals in maintaining cerebral perfusion during focal arterial occlusions, regulation of microvascular blood flow and oxygenation in the cerebral watershed “pial-collateral territory” during chronic hypoperfusion remains unexplored. To answer this question, we applied 2-photon microscopy and Doppler optical coherence tomography to assess the changes in cerebral blood flow, capillary red-blood-cell (RBC) flux, and intravascular oxygen partial pressure (PO₂), seven days after bilateral common-carotid artery stenosis (BCAS). The measurements were performed in the middle-cerebral-artery (MCA) territory and the watershed between the MCA and anterior-cerebral-artery territories in the awake, head-restrained C57BL/6 mice, through a glass-sealed cranial window. The results showed that BCAS induced a significant decrease in microvascular perfusion in the watershed area compared to the MCA territory, with the largest RBC flux reduction observed in the subcortical white matter. The watershed area exhibited a larger drop between arterial and venous PO₂ and the calculated oxygen saturation, indicating a significant increase in oxygen extraction fraction following BCAS. Structural analysis of the microvasculature showed significant BCAS-induced dilation of pial collaterals, suggesting a potential compensatory mechanism to improve blood flow in the hypoperfused watershed. However, microvascular morphology did not change in either region, implying an absence of structural remodeling at this early stage. Collectively, these findings point to an oxygen supply-consumption mismatch and heightened vulnerability in the watershed areas, particularly affecting the subcortical white matter, during flow-limiting cervical artery stenosis.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115666"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046322","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":"The crosstalk between chaperone-mediated autophagy and apoptosis via ATM/p53-mitochondria-dependent signaling contributed to ischemia-induced cerebral injuries","authors":"Qiandai Hu ,&nbsp;Yiyun Wang ,&nbsp;Jiahui Fan ,&nbsp;Xueyu Hou,&nbsp;Yan Zhou,&nbsp;Yanling Yin","doi":"10.1016/j.expneurol.2026.115673","DOIUrl":"10.1016/j.expneurol.2026.115673","url":null,"abstract":"<div><div>Stroke is the second leading cause of death and a leading cause of disability worldwide. Neuronal loss is a significant factor in determining the outcome of ischemic stroke. However, there is no effective treatment for neuronal loss caused by stroke. This study found that acute ischemia upregulated chaperone-mediated autophagy (CMA) levels in both in vivo and in vitro models. Further, it was observed that inhibition of CMA with pharmacological intervention or LAMP2A knockdown (KD) ameliorated neuronal loss induced by acute ischemia. In addition, inhibition of CMA before or upon acute ischemia can significantly reduce the infarct size and restore neurological function, indicating that a CMA-targeted strategy may facilitate the outcomes of acute ischemic stroke. Notably, pharmacological intervention for CMA under normoxia conditions did not significantly affect neuronal survival. Meanwhile, intervention to CMA upregulation upon the acute ischemia may prevent the decreased CMA in the recovery stage of cerebral ischemia. Moreover, since mitochondrial dysfunction plays a vital role in the initiation and activation of apoptosis, the role of CMA in neuronal mitochondrial function was observed with MitoSOX and TMRM staining. It was found that CMA upregulation contributed to oxygen-glucose deprivation (OGD)-induced mitochondrial injuries. Based on the reported association between ataxia telangiectasia mutated (ATM)-mitochondria signaling and p53 in the occurrence of apoptosis, the activation of p53 was evidenced as the downstream event of the ATM-mitochondria signaling and played a vital role in apoptosis upon OGD. Our current study indicates that there is crosstalk between autophagy and apoptosis. These findings highlight the critical role of CMA in the outcomes of ischemic stroke and implicate its potential application in stroke therapy.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115673"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097091","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":"Monocyte-derived macrophages promote retinal damage after ischemic stroke via IL-1β-dependent mechanism","authors":"Hong-Bin Lin ,&nbsp;Jin-Yu Zhang ,&nbsp;Meng Li ,&nbsp;Xiang-Xiong Pang ,&nbsp;Zhang-Rui Shi ,&nbsp;Ke Li ,&nbsp;Xiao-Long Cao ,&nbsp;Fengxian Li ,&nbsp;Hong-Fei Zhang","doi":"10.1016/j.expneurol.2026.115676","DOIUrl":"10.1016/j.expneurol.2026.115676","url":null,"abstract":"<div><div>Vision impairment following ischemic stroke is a prevalent complication that significantly compromises patients' quality of life. Inflammatory responses critically contribute to retinal dysfunction in this condition. Retinal myeloid cells contributed to the retinal inflammatory response, which presented heterogeneity after retinal injury. In this study, we employed the classical middle cerebral artery occlusion (MCAO) mouse model to simulate ischemic stroke. We demonstrated that stroke-induced retinal damage manifests as diminished photoreceptor responses and increased retinal cell apoptosis by using electroretinogram, TdT-mediated dUTP Nick-End Labeling and hematoxylin-eosin staining. Furthermore, we observed myeloid cell infiltration into the retina post-stroke and retinal inflammatory activation after stroke via immunofluorescence staining, retinal bulk RNA sequencing and luminex assay. Through retinal single-cell RNA sequencing, <em>Cx3cr1</em>^<em>GFP</em><em>Ccr2</em>^<em>RFP</em> reporter mice and CCL2 neutralizing antibodies interventions, we observed that infiltrating monocyte-derived macrophages expand and exhibit a predominantly pro-inflammatory phenotype in the retina following stroke. Subsequent experiments utilizing IL-1β neutralizing antibodies and <em>Nlrp3</em>-deficient mice established that IL-1β derived from monocyte-derived macrophages promotes ischemic stroke-induced retinal damage. Collectively, our findings demonstrate that monocyte-derived macrophages drive retinal pathology after ischemic stroke via IL-1β-dependent mechanisms.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115676"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100186","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":"Dendritic spine dysgenesis in spinal cord injury: A structural contributor to pain and spasticity","authors":"Sierra D. Kauer ,&nbsp;Philip R. Effraim ,&nbsp;Lakshmi Bangalore ,&nbsp;Stephen G. Waxman ,&nbsp;Andrew M. Tan","doi":"10.1016/j.expneurol.2026.115679","DOIUrl":"10.1016/j.expneurol.2026.115679","url":null,"abstract":"<div><div>Pain and spasticity are common consequences of spinal cord injury (SCI) that profoundly diminish quality of life. Although pain arises from sensory pathways and spasticity from motor pathways, both reflect post-injury mechanisms that renders spinal circuits hyperexcitable. Dendritic spines—specialized protrusions on neuronal dendrites that mediate excitatory synaptic transmission—undergo striking structural remodeling after SCI. Abnormal spine morphology has been documented in both the superficial and deeper laminae of the dorsal horn, correlating with pain, and on motor neurons in the lumbar spinal cord after, correlating with spasticity. These abnormalities include: (i) increased spine density, (ii) redistribution of spines closer to the soma, and (iii) enlargement of spine heads. A growing body of evidence implicates dysregulation of the Rac1-PAK1 signaling pathway in driving these changes, and pharmacologic inhibition of this pathway can reverse these dendritic spine dysgeneses and attenuate circuit hyperexcitability in preclinical models. This review examines dendritic spine pathology as a shared mechanistic substrate linking pain and spasticity after SCI and highlights dendritic spines and their regulatory pathways a promising therapeutic target for intervention.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115679"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137352","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":"Role of glycolysis-mediated histone lactylation in microglial activation and progression of neurodegenerative diseases","authors":"Shuaikang Wang ,&nbsp;Jingjing Wang ,&nbsp;Zhiying Hu ,&nbsp;Li Wu ,&nbsp;Liping Huang","doi":"10.1016/j.expneurol.2026.115663","DOIUrl":"10.1016/j.expneurol.2026.115663","url":null,"abstract":"<div><div>Microglia-mediated neuroinflammation is a key driver of neurodegenerative disease progression, yet the metabolic mechanisms underlying microglial dysfunction remain poorly understood. Recent studies highlight glycolytic reprogramming in activated microglia, which generates lactate that, in turn, promotes histone lactylation, an epigenetic modification that significantly alters gene expression. This glycolysis-histone lactylation axis has been implicated in Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders, where its dysregulation exacerbates chronic neuroinflammation and neuronal damage. Despite this, the precise molecular mechanisms linking microglial metabolic shifts to epigenetic remodeling and disease pathogenesis are not fully defined. This review consolidates current knowledge on how the glycolysis-histone lactylation pathway influences microglial phenotypes and function in neurodegenerative contexts. We explore the molecular machinery driving lactate-mediated histone modifications, their transcriptional consequences, and their pathological impact on disease progression. Importantly, we discuss emerging therapeutic strategies targeting this metabolic-epigenetic axis, including glycolysis inhibitors and lactylation modulators, as promising precision medicine approaches for neurodegenerative diseases. By elucidating these mechanisms, this review provides a framework for developing metabolism-based interventions aimed at restoring microglial homeostasis and slowing neurodegeneration.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115663"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040588","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":"Palmitoylethanolamide ameliorates postoperative cognitive dysfunction via microglial PPARα-mediated anti-inflammatory and neuroprotective mechanisms","authors":"Xiaojun Zhang ,&nbsp;Wensi Wu ,&nbsp;Zhenzhen Zheng ,&nbsp;Guijie Liu ,&nbsp;Dongliang Li ,&nbsp;Liang Li","doi":"10.1016/j.expneurol.2026.115664","DOIUrl":"10.1016/j.expneurol.2026.115664","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a frequent neurological complication characterized by memory and learning impairments in the elderly, while effective pharmacological interventions remain limited. Palmitoylethanolamide (PEA), an endogenous lipid mediator with anti-inflammatory and neuroprotective properties, has emerged as a potential therapeutic candidate.</div></div><div><h3>Methods</h3><div>An aged mouse model of POCD was used to evaluate the effects of PEA. Cognitive performance was assessed by the open field test, novel object recognition, and Barnes maze. Neuroinflammation, microglial activation, neuronal integrity, and synaptic plasticity–related proteins were assessed using immunostaining and molecular analyses both in vivo and in vitro. To determine the role of peroxisome proliferator-activated receptor-α (PPARα), stereotaxic delivery of shPPARα virus to prefrontal cortex (PFC) microglia was performed.</div></div><div><h3>Results</h3><div>PEA treatment significantly improved both short- and long-term memory in aged POCD mice. Mechanistically, PEA attenuated microglial activation, shifted microglial activation toward the anti-inflammatory phenotype, preserved neuronal survival, and upregulated synaptic plasticity-associated proteins. Importantly, PEA restored PPARα activity, and knockdown of PPARα abolished these protective effects both in vivo and in vitro, confirming its essential role.</div></div><div><h3>Conclusions</h3><div>PEA alleviates cognitive deficits in aged POCD mice by enhancing PPARα signaling, reducing neuroinflammation, and promoting neuronal protection. These findings support PEA as a promising therapeutic strategy for the treatment of aged POCD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115664"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040577","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":"Integrated miRNA-proteomic profiling identifies chronic vesicle-trafficking and proteostasis disruptions after mild traumatic brain injury","authors":"Hamad Yadikar ,&nbsp;Mubeen A. Ansari","doi":"10.1016/j.expneurol.2026.115652","DOIUrl":"10.1016/j.expneurol.2026.115652","url":null,"abstract":"<div><h3>Background</h3><div>Mild traumatic brain injury (mTBI) often produces persistent deficits, yet the molecular mechanisms driving chronic pathology remain undefined.</div></div><div><h3>Objective</h3><div>We aimed to identify mechanistic drivers of long-term dysfunction after mTBI by integrating proteomics, transcriptomics, and behavioral outcomes.</div></div><div><h3>Methods</h3><div>Adult rats were subjected to a modified Marmarou weight-drop mTBI model (diffuse closed-head injury) or a sham procedure. Cortical tissue was analyzed at 21 days post-injury (chronic phase) by quantitative proteomics and small RNA sequencing, while neurological and motor functions were tracked longitudinally (subacute to chronic phases). Key molecular changes were validated via Western blotting and RT-qPCR.</div></div><div><h3>Results</h3><div>mTBI induced widespread and persistent alterations in cortical protein expression, particularly affecting vesicle-trafficking and proteostasis-related pathways. Several proteins—including Rab11b, Dnm2, TIA1, Snx30, Sbf1, and Vma21—exhibited robust decreases across both proteomic and immunoblot analyses, indicating reproducible impairment of endosomal recycling and stress-response mechanisms. Cavin-2 and COMMD2 showed significant fold changes at the proteomic level but were not entirely validated and therefore remain preliminary observations. Differentially expressed miRNAs exhibited coordinated regulatory patterns, and integrated miRNA–protein signatures achieved high discriminatory performance (AUC &gt; 0.95) in separating injured from control animals.</div></div><div><h3>Conclusions</h3><div>These findings demonstrate that even an mTBI causes enduring disruptions in protein homeostasis, vesicle trafficking, and post-transcriptional regulation, which correlate with chronic behavioral deficits. The injury-responsive networks identified provide a systems-level foundation for future mechanistic studies and highlight promising candidate biomarkers to improve mTBI diagnosis and monitoring.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115652"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075846","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}