Experimental Neurology最新文献

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Anesthesia/surgery leads to blood-brain barrier disruption via the transcellular and paracellular pathways, and postoperative delirium-like behavior: A comparative study in mice of different ages. 麻醉/手术会通过跨细胞和旁细胞途径导致血脑屏障破坏,并导致术后类似谵妄的行为:不同年龄小鼠的比较研究。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-11-04 DOI: 10.1016/j.expneurol.2024.115044
Xudong Hu, Lixia Liu, Xin Da, Sihui Zhu, Jiawei Wang, Menglei Shan, Yinuo Liu, Ziqing He, Guanghong Xu
{"title":"Anesthesia/surgery leads to blood-brain barrier disruption via the transcellular and paracellular pathways, and postoperative delirium-like behavior: A comparative study in mice of different ages.","authors":"Xudong Hu, Lixia Liu, Xin Da, Sihui Zhu, Jiawei Wang, Menglei Shan, Yinuo Liu, Ziqing He, Guanghong Xu","doi":"10.1016/j.expneurol.2024.115044","DOIUrl":"https://doi.org/10.1016/j.expneurol.2024.115044","url":null,"abstract":"<p><strong>Aims: </strong>Postoperative delirium (POD) is a common complication of anesthesia and surgery, with a higher incidence in elderly patients. Disruption of the blood-brain barrier (BBB) is considered one of the key mechanisms underlying POD. Therefore, the present study aimed to investigate the effects of different BBB permeability alteration pathways on POD in mice of various ages.</p><p><strong>Methods: </strong>C57BL/6 J mice aged 4 and 16 months underwent exploratory laparotomy under sevoflurane anesthesia. Behavioral tests were conducted 24 h prior to surgery, as well as 6, 9, and 24 h postoperatively. Frontal cortex tissue was collected to detect the levels of BBB-related proteins and mRNA.</p><p><strong>Results: </strong>At 6 and 9 h after anesthesia/surgery, 4-month-old mice showed poorer performance on behavioral tests than their untreated counterparts. However, 16-month-old mice exhibited worse behavioral test results at 6, 9, and 24 h after surgery. Anesthesia/surgery 6 h postoperatively increased the expression of vesicle-associated proteins, and BBB leakage in 4-month-old mice. In 16-month-old mice, anesthesia/surgery altered the expression of tight junction proteins, vesicle-associated proteins, and BBB leakage at 6 and 24 h postoperatively.</p><p><strong>Conclusion: </strong>Overall, our results suggest that anesthesia/surgery leads to age-dependent cognitive decline, and is associated with differences in the BBB injury pathways among mice of different ages. The transcellular pathway (transcytosis), compared to the paracellular pathway (tight junction), is more vulnerable to damage following anesthesia/surgery. This study provides new evidence for the improvement of POD through protection of the BBB.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589652","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}
引用次数: 0
Temporal development of seizure threshold and spontaneous seizures after neonatal asphyxia and the effect of prophylactic treatment with midazolam in rats. 新生儿窒息后大鼠癫痫阈值和自发性癫痫发作的时间发展以及咪达唑仑预防性治疗的影响
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-11-04 DOI: 10.1016/j.expneurol.2024.115042
Ricardo Schmidt, Björn Welzel, Annika Merten, Hannah Naundorf, Wolfgang Löscher
{"title":"Temporal development of seizure threshold and spontaneous seizures after neonatal asphyxia and the effect of prophylactic treatment with midazolam in rats.","authors":"Ricardo Schmidt, Björn Welzel, Annika Merten, Hannah Naundorf, Wolfgang Löscher","doi":"10.1016/j.expneurol.2024.115042","DOIUrl":"10.1016/j.expneurol.2024.115042","url":null,"abstract":"<p><p>Birth asphyxia (BA) and subsequent hypoxic-ischemic encephalopathy (HIE) is one of the most serious birth complications affecting full-term infants and can result in severe disabilities including mental retardation, cerebral palsy, and epilepsy. Animal models of BA and HIE are important to characterize the functional and behavioral correlates of injury, explore cellular and molecular mechanisms, and assess the potential of novel therapeutic strategies. Here we used a non-invasive, physiologically validated rat model of BA and acute neonatal seizures that mimics many features of BA and HIE in human infants to study (i) the temporal development of epilepsy with spontaneous recurrent seizures (SRS) in the weeks and months after the initial brain injury, (ii) alterations in seizure threshold and hippocampal EEG that may precede the onset of SRS, and (iii) the effect of prophylactic treatment with midazolam. For this purpose, a total of 89 rat pups underwent asphyxia or sham asphyxia at postnatal day 11 and were examined over 8-10.5 months. In vehicle-treated animals, the incidence of electroclinical SRS progressively increased from 0 % at 2.5 months to 50 % at 6.5 months, 75 % at 8.5 months, and > 80 % at 10.5 months after asphyxia. Unexpectedly, post-asphyxial rats did not differ from sham-exposed rats in seizure threshold or interictal epileptiform discharges in the EEG. Treatment with midazolam (1 mg/kg i.p.) after asphyxia, which suppressed acute symptomatic neonatal seizures in about 60 % of the rat pups, significantly reduced the incidence of SRS regardless of its effect on neonatal seizures. This antiepileptogenic effect of midazolam adds to the recently reported prophylactic effects of this drug on BA-induced neuroinflammation, brain damage, behavioral alterations, and cognitive impairment in the rat asphyxia model of HIE.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589807","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}
引用次数: 0
Early α-synuclein/synapsin III co-accumulation, nigrostriatal dopaminergic synaptopathy and denervation in the MPTPp mouse model of Parkinson's Disease. 帕金森病 MPTPp 小鼠模型的早期α-突触核蛋白/突触核蛋白 III 共同积累、黑质纹状体多巴胺能突触病变和神经支配。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-11-03 DOI: 10.1016/j.expneurol.2024.115040
Marcello Serra, Gaia Faustini, Viviana Brembati, Maria Antonietta Casu, Marina Pizzi, Micaela Morelli, Annalisa Pinna, Arianna Bellucci
{"title":"Early α-synuclein/synapsin III co-accumulation, nigrostriatal dopaminergic synaptopathy and denervation in the MPTPp mouse model of Parkinson's Disease.","authors":"Marcello Serra, Gaia Faustini, Viviana Brembati, Maria Antonietta Casu, Marina Pizzi, Micaela Morelli, Annalisa Pinna, Arianna Bellucci","doi":"10.1016/j.expneurol.2024.115040","DOIUrl":"10.1016/j.expneurol.2024.115040","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by the loss of nigrostriatal dopaminergic neurons and the presence of Lewy bodies (LB), intraneuronal inclusions mainly composed of α-synuclein (α-Syn) fibrils. Compelling evidence supports that, in PD brains, synapses are the sites where neurodegeneration initiates several years before the manifestation of motor symptoms. Furthermore, the amount of α-Syn deposited at synaptic terminals is several orders greater than that constituting LB. This hints that pathological synaptic α-Syn aggregates may be the main trigger for the retrograde synapse-to-cell body degeneration pattern characterizing early prodromal phases of PD. Identifying reliable biomarkers of synaptopathy is therefore crucial for early diagnosis. Here, we studied the alterations of key dopaminergic and non-dopaminergic striatal synaptic markers during the initial phases of axonal and cell body degeneration in mice subjected to 3 or 10 administrations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + probenecid (MPTPp), a model for early prodromal PD. We found that MPTPp administration resulted in progressive deposition of α-Syn, advancing from synaptic terminals to axons and dopaminergic neuron cell bodies. This was accompanied by marked co-accumulation of Synapsin III (Syn III), a synaptic protein previously identified as a component of α-Syn fibrils in post-mortem PD brains and as a main stabilizer of α-Syn aggregates, as well as very early and severe reduction of vesicular monoamine transporter 2 (VMAT2), dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunoreactivity in nigrostriatal neurons. Results also showed that striatal α-Syn accumulation and VMAT2 decrease, unlike other markers, did not recover following washout from 10 MPTPp administrations, supporting that these changes were precocious and severe. Finally, we found that early changes in striatal α-Syn, Syn III, VMAT2 and DAT observed following 3 MPTPp administrations, correlated with nigrostriatal neuron loss after 10 MPTPp administrations. These findings indicate that α-Syn/Syn III co-deposition characterizes very early stages of striatal dopaminergic dysfunction in the MPTPp model and highlight that VMAT2 and Syn III could be two reliable molecular imaging biomarkers to predict dopamine neuron denervation and estimate α-Syn-related synaptopathy in prodromal and early symptomatic phases of PD.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581877","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}
引用次数: 0
Comparing white and gray matter responses to lobar intracerebral hemorrhage in piglets and the effects of deferoxamine. 比较仔猪脑叶内出血时白质和灰质的反应以及去氧胺的作用。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-11-01 DOI: 10.1016/j.expneurol.2024.115041
Yingfeng Wan, Qing Xie, Ya Hua, Guohua Xi, Richard F Keep, Aditya Pandey
{"title":"Comparing white and gray matter responses to lobar intracerebral hemorrhage in piglets and the effects of deferoxamine.","authors":"Yingfeng Wan, Qing Xie, Ya Hua, Guohua Xi, Richard F Keep, Aditya Pandey","doi":"10.1016/j.expneurol.2024.115041","DOIUrl":"10.1016/j.expneurol.2024.115041","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) often impacts patient white matter. However, preclinically, the effects of ICH are mostly studied in rodents with sparse white matter. This study used a lobar porcine ICH model to examine differences in the effects of ICH on white and gray matter as well as the role of the iron chelator deferoxamine (DFX), on attenuation of such injury.</p><p><strong>Methods: </strong>This two-part study was performed in piglets. Firstly, piglets had a needle (Sham) or 2.5 ml blood injection (ICH) and were euthanized at day 3. Secondly, animals were treated with vehicle or DFX after ICH and were euthanized at day 3. White and gray matter edema, the number of oligodendrocytes (mature and immature) and neurons, and the number of Perls' (iron), ferritin and heme oxygenase (HO)-1 positive cells were examined.</p><p><strong>Results: </strong>At day 3, ICH induced greater edema formation in white than gray matter. This marked white matter edema was associated with a loss of mature, but not immature, oligodendrocytes. ICH also induced neuronal death in gray matter. There were also marked increases in Perls', ferritin and HO-1 positive cells after ICH in both white and gray matter, but significantly more in the former. DFX attenuated ICH-induced brain edema in white but not gray matter and this was associated with increased survival of mature oligodendrocytes. DFX also increased survival of neurons in the gray matter and it reduced the number of Perls', ferritin and HO-1 positive cells in both tissue types.</p><p><strong>Conclusions: </strong>While there were commonalities in perihematomal changes between white and gray matter after ICH, there was greater edema in white matter which may be linked to the susceptibility of mature oligodendrocytes to ICH injury. Similarly, while DFX reduced perihematomal iron overload in both white and gray matter, it only significantly reduced edema in white matter where it increased the number of mature oligodendrocytes.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566616","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}
引用次数: 0
Multifaceted role of thrombin in subarachnoid hemorrhage: Focusing on cerebrospinal fluid circulation disorder. 凝血酶在蛛网膜下腔出血中的多重作用:关注脑脊液循环障碍。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-30 DOI: 10.1016/j.expneurol.2024.115036
Yajun Qian, Junjie Wang, Jiarui Chen, Weibo Lin, Huimin Shen, Yuanjian Fang, Wenhua Yu
{"title":"Multifaceted role of thrombin in subarachnoid hemorrhage: Focusing on cerebrospinal fluid circulation disorder.","authors":"Yajun Qian, Junjie Wang, Jiarui Chen, Weibo Lin, Huimin Shen, Yuanjian Fang, Wenhua Yu","doi":"10.1016/j.expneurol.2024.115036","DOIUrl":"https://doi.org/10.1016/j.expneurol.2024.115036","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) is a severe neurological condition characterized by high morbidity and mortality. The unfavorable prognosis of SAH is closely associated with early brain injury (EBI) and delayed cerebral ischemia (DCI), wherein thrombin plays a role as part of the secondary injury components following hemorrhage in these two pathological processes. Additionally, thrombin contributes to disruptions in the circulation of cerebrospinal fluid (CSF), thereby giving rise to a spectrum of sequelae following SAH, including cerebral edema, hydrocephalus, cognitive impairments, and depressive symptoms. This review aims to provide a comprehensive understanding of the pathological role of thrombin in EBI, DCI, and CSF circulation following SAH, with a specific focus on its impact on the glymphatic-meningeal lymphatic system-a crucial mechanism for waste clearance and neurohomeostatic regulation. Additionally, this review offers an overview of current pharmacological interventions and treatment modalities targeting pathogenic mechanisms, aiming to mitigate brain injury and promote neurological recovery post-SAH.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563639","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}
引用次数: 0
Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus. 下丘脑外侧神经肽神经元对觉醒的调节
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-29 DOI: 10.1016/j.expneurol.2024.115035
Fumito Naganuma, Mudasir Khanday, Sathyajit Sai Bandaru, Whidul Hasan, Kyosuke Hirano, Takeo Yoshikawa, Ramalingam Vetrivelan
{"title":"Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus.","authors":"Fumito Naganuma, Mudasir Khanday, Sathyajit Sai Bandaru, Whidul Hasan, Kyosuke Hirano, Takeo Yoshikawa, Ramalingam Vetrivelan","doi":"10.1016/j.expneurol.2024.115035","DOIUrl":"10.1016/j.expneurol.2024.115035","url":null,"abstract":"<p><p>The lateral hypothalamic region (LH) has been identified as a key region for arousal regulation, yet the specific cell types and underlying mechanisms are not fully understood. While neurons expressing orexins (OX) are considered the primary wake-promoting population in the LH, their loss does not reduce daily wake levels, suggesting the presence of additional wake-promoting populations. In this regard, we recently discovered that a non-OX cell group in the LH, marked by the expression of neurotensin (Nts), could powerfully drive wakefulness. Activation of these Nts<sup>LH</sup> neurons elicits rapid arousal from non-rapid eye movement (NREM) sleep and produces uninterrupted wakefulness for several hours in mice. However, it remains unknown if these neurons are necessary for spontaneous wakefulness and what their precise role is in the initiation and maintenance of this state. To address these questions, we first examined the activity dynamics of the Nts<sup>LH</sup> population across sleep-wake behavior using fiber photometry. We find that Nts<sup>LH</sup> neurons are more active during wakefulness, and their activity increases concurrently with, but does not precede, wake-onset. We then selectively destroyed the Nts<sup>LH</sup> neurons using a diphtheria-toxin-based conditional ablation method, which significantly reduced wake amounts and mean duration of wake bouts and increased the EEG delta power during wakefulness. These findings demonstrate a crucial role for Nts<sup>LH</sup> neurons in maintaining normal arousal levels, and their loss may be associated with chronic sleepiness in mice.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557502","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}
引用次数: 0
Lactate supplementation after hypoglycemia alleviates cognitive dysfunction induced by recurrent non-severe hypoglycemia in diabetic mice 低血糖后补充乳酸可减轻糖尿病小鼠因反复发生非严重低血糖而导致的认知功能障碍。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-29 DOI: 10.1016/j.expneurol.2024.115037
{"title":"Lactate supplementation after hypoglycemia alleviates cognitive dysfunction induced by recurrent non-severe hypoglycemia in diabetic mice","authors":"","doi":"10.1016/j.expneurol.2024.115037","DOIUrl":"10.1016/j.expneurol.2024.115037","url":null,"abstract":"<div><div>Recurrent non-severe hypoglycemia (RH) in diabetes is an independent risk factor for cognitive dysfunction. However, the mechanisms and potential therapeutic strategies remain poorly understood. In this study, we aimed to elucidate the mechanisms underlying RH-induced diabetic cognitive impairment. We investigated the effects of RH on lactate metabolism and cognitive function in male C57BL/6 J diabetic mice. After RH, diabetic mice showed decreased brain lactate and adenosine triphosphate levels, decreased expression of lactate transporter proteins MCT1 and MCT4, increased neuroapoptosis, and decreased astrocyte glycolysis in vitro. This was accompanied by increased neuronal mitochondrial reactive oxygen species levels, decreased mitochondrial COX IV activity, impaired mitochondrial morphology and function, impaired synaptic morphology, and decreased expression of synaptic plasticity proteins. Intraperitoneal lactic acid injection improved lactate transport restored neuronal mitochondrial morphology and function, upregulated synaptic plasticity proteins brain-derived neurotrophic factor and early growth response 1, enhanced synaptic ultrastructure, and ultimately improved cognitive dysfunction following RH in diabetic mice. These findings provide insights into the prevention and treatment of cognitive dysfunction in patients with diabetes mellitus caused by RH.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557499","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}
引用次数: 0
Multiple strategies enhance the efficacy of MSC-Exos transplantation for spinal cord injury 多种策略提高了间充质干细胞-Exos 移植治疗脊髓损伤的疗效。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-29 DOI: 10.1016/j.expneurol.2024.115038
{"title":"Multiple strategies enhance the efficacy of MSC-Exos transplantation for spinal cord injury","authors":"","doi":"10.1016/j.expneurol.2024.115038","DOIUrl":"10.1016/j.expneurol.2024.115038","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a relatively common and lethal dangerous disease of the central nervous system, for which there is a lack of effective clinical treatments. It has been found that mesenchymal stem cell-derived exosomes (MSC-Exos) play a key role in alleviating SCI through mechanisms such as regulating the microenvironment, promoting angiogenesis, and facilitating axonal regeneration. However, the drawbacks of natural exosomes, such as low yield, weak activity, and low targeting ability, limit their clinical applications. In recent years, MSCs-Exos have gradually become a research hotspot for treating SCI through miRNA modulation, combined hydrogel, and preculture. In addition, exosomes as good biocompatible drugs, nucleic acid, and other delivery carriers have shown a broad application prospect in treating SCI. This article summarizes the pathogenesis of SCI and the research progress of MSC-Exos in the treatment of SCI in recent years, and provides a systematic review of the mechanisms of MSC exosomes and their combination with different modalities in the treatment of SCI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557500","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}
引用次数: 0
No impact of anti-inflammatory medication on inflammation-driven recovery following cervical spinal cord injury in rats. 抗炎药物对大鼠颈脊髓损伤后的炎症驱动恢复没有影响。
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-29 DOI: 10.1016/j.expneurol.2024.115039
Jaison Cucarian, Pamela Raposo, Romana Vavrek, Antoinette Nguyen, Brooklynn Nelson, Philippe Monnier, Abel Torres-Espin, Keith Fenrich, Karim Fouad
{"title":"No impact of anti-inflammatory medication on inflammation-driven recovery following cervical spinal cord injury in rats.","authors":"Jaison Cucarian, Pamela Raposo, Romana Vavrek, Antoinette Nguyen, Brooklynn Nelson, Philippe Monnier, Abel Torres-Espin, Keith Fenrich, Karim Fouad","doi":"10.1016/j.expneurol.2024.115039","DOIUrl":"https://doi.org/10.1016/j.expneurol.2024.115039","url":null,"abstract":"<p><p>Following spinal cord injury (SCI), inflammation is associated with the exacerbation of damage to spinal tissue. Consequently, managing inflammation during the acute and subacute phases is a common target in SCI treatment. However, inflammation may also induce potential benefits, including the stimulation of neuroplasticity and repair. This positive role of inflammation in spinal cord healing and functional recovery is not fully understood. To address this knowledge gap, we examined the effects of two common anti-inflammatory medications, Diphenhydramine and Methylprednisolone, on the efficacy of rehabilitative motor training on recovery from subacute cervical SCI in adult rats. Training depends critically on neuroplasticity thus if inflammation is a key regulator, we propose that anti-inflammatory drugs will reduce subsequent recovery. Both drugs were administered orally over one month, alongside task-specific reaching and grasping training. After treatment, no substantial changes in motor recovery or lesion size between the treated and control groups were observed. Treated animals also did not show any discernible changes in sensory function or anxiety-like behavior. Taken together, our data indicate that the prolonged use of these anti-inflammatory agents at commonly used doses did not profoundly impact recovery following an SCI. Therefore, considering earlier reports of the benefits of pro-inflammatory stimuli on plasticity, further studies in this area are imperative to elucidate the true impact of treating inflammation and its implications for recovery after spinal cord injuries.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557501","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}
引用次数: 0
Upregulation of Nav1.6 expression in the ventral posterolateral nucleus of thalamus contributes to hyperalgesia in a model of Parkinson's disease 丘脑腹侧后外侧核中 Nav1.6 表达的上调有助于帕金森病模型中的痛觉亢进
IF 4.6 2区 医学
Experimental Neurology Pub Date : 2024-10-28 DOI: 10.1016/j.expneurol.2024.115032
{"title":"Upregulation of Nav1.6 expression in the ventral posterolateral nucleus of thalamus contributes to hyperalgesia in a model of Parkinson's disease","authors":"","doi":"10.1016/j.expneurol.2024.115032","DOIUrl":"10.1016/j.expneurol.2024.115032","url":null,"abstract":"<div><div>Pain is the most common non-motor manifestation of Parkinson's disease (PD), affecting the quality of life for patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals. Here we investigated the expression patterns of Nav1.6 in the ventral posterolateral (VPL) nucleus of the thalamus and its involvement in the development of hyperalgesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. The results showed a significant increase in Nav1.6 expression in reactive astrocytes of the ipsilateral VPL in 6-OHDA-lesioned rats at 4 weeks post-injection. Moreover, 6-OHDA-lesioned rats exhibited mechanical hyperalgesia, but did not display thermal hyperalgesia in the ipsilateral paw at the same time point. The down-regulation of Nav1.6 in the ipsilateral VPL can reduce mechanical hyperalgesia and improve sensorimotor impairments in 6-OHDA- lesioned rats. Furthermore, the analysis of local field potentials (LFPs) revealed that the increased Nav1.6 may participate in abnormal synchronized oscillations within the thalamocortical loop in 6-OHDA-lesioned rats. These findings suggest that the altered expression of Nav1.6 in astrocytes of the VPL may play an important role in the abnormal processing of pain within the thalamocortical circuit, contributing to the formation of mechanical hyperalgesia in animal models of PD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555015","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}
引用次数: 0
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