Repetitive head trauma and apoE4 induce chronic cerebrovascular alterations that impair tau elimination from the brain
Exp Neurol. 2024 Jan 30;374:114702. doi: 10.1016/j.expneurol.2024.114702. Online ahead of print.ABSTRACTRepetitive mild traumatic brain injuries (r-mTBI) sustained in the military or contact sports have been associated with the accumulation of extracellular tau in the brain, which may contribute to the pathogenesis of neurodegenerative tauopathies. The expression of the apolipoprotein E4 (apoE4) isoform has been associated with higher levels of tau in the brain, and worse clinical outcomes after r-mTBI, though the influence of apoE genotype on extracellular tau dynamics in the brain is poorly understood. We recently demons...
Source: Experimental Neurology - February 1, 2024 Category: Neurology Authors: Maxwell Eisenbaum Andrew Pearson Camila Ortiz Milica Koprivica Arianna Cembran Michael Mullan Fiona Crawford Joseph Ojo Corbin Bachmeier Source Type: research
Neuroinflammation, blood-brain barrier dysfunction, hippocampal atrophy and delayed neurodevelopment: Contributions for a rat model of congenital Zika syndrome
This study aimed to investigate the consequences of a model of congenital ZIKV infection by evaluating the histopathology, blood-brain barrier, and neuroinflammation in pup rats 24 h after birth, and neurodevelopment of the offspring. Pregnant rats were inoculated subcutaneously with ZIKV-BR at the dose 1 × 107 plaque-forming unit (PFU mL-1) of ZIKV isolated in Brazil (ZIKV-BR) on gestational day 18 (G18). A set of pups, 24 h after birth, was euthanized. The brain was collected and later evaluated for the histopathology of brain structures through histological analysis. Additionally, analyses of the blood-brain barrier we...
Source: Experimental Neurology - February 1, 2024 Category: Neurology Authors: Adriana Souza Dos Santos Meirylanne Gomes da Costa Aline Martins Faustino Wellington de Almeida Chris Krebs Danilevicz Ariadni Mesquita Peres Bruna Carolina de Castro Saturnino Ana Paula Muterle Varela Thais Fumaco Teixeira Paulo Michel Roehe Rachel Krolo Source Type: research
Inhibiting RIPK1-driven neuroinflammation and neuronal apoptosis mitigates brain injury following experimental subarachnoid hemorrhage
In this study, we established in vivo and in vitro models of SAH to investigate the activation of RIPK1 kinase in both microglia and neurons. We observed the correlation between RIPK1 kinase activity and microglia-mediated inflammation as well as neuronal apoptosis. We then investigated whether inhibition of RIPK1 could alleviate neuroinflammation and neuronal apoptosis following SAH, thereby reducing brain edema and ameliorating neurobehavioral deficits. Additionally, the underlying mechanisms were also explored. Our research findings revealed the activation of RIPK1 kinase in both microglia and neurons following SAH, as ...
Source: Experimental Neurology - January 30, 2024 Category: Neurology Authors: Yan Wu Yao Xu Jingshan Sun Kun Dai Zhong Wang Jian Zhang Source Type: research
Positive relation between dopamine neuron degeneration and metabolic connectivity disruption in the MPTP plus probenecid mouse model of Parkinson's disease
Exp Neurol. 2024 Jan 26;374:114704. doi: 10.1016/j.expneurol.2024.114704. Online ahead of print.ABSTRACTThe clinical manifestation of Parkinson's disease (PD) appears when neurodegeneration is already advanced, compromising the efficacy of disease-modifying treatment approaches. Biomarkers to identify the early stages of PD are therefore of paramount importance for the advancement of the therapy of PD. In the present study, by using a mouse model of PD obtained by subchronic treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the clearance inhibitor probenecid (MPTPp), we identified prodro...
Source: Experimental Neurology - January 28, 2024 Category: Neurology Authors: Margherita Tassan Mazzocco Marcello Serra Marco Maspero Angela Coliva Luca Presotto Maria Antonietta Casu Micaela Morelli Rosa Maria Moresco Sara Belloli Annalisa Pinna Source Type: research
Mitochondrial ferritin upregulation reduced oxidative stress and blood-brain-barrier disruption by maintaining cellular iron homeostasis in a neonatal rat model of germinal matrix hemorrhage
Exp Neurol. 2024 Jan 26;374:114703. doi: 10.1016/j.expneurol.2024.114703. Online ahead of print.ABSTRACTGerminal matrix hemorrhage (GMH) is a devasting neurological disease in premature newborns. After GMH, brain iron overload associated with hemoglobin degradation contributed to oxidative stress, causing disruption of the already vulnerable blood-brain barrier (BBB). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, is crucial in maintaining cellular iron homeostasis. We aimed to investigate the effect of FTMT upregulation on oxidative stress and BBB disruption associated with brain iron overloa...
Source: Experimental Neurology - January 28, 2024 Category: Neurology Authors: Ye Yuan Qiuguang He Xiao Yang Jerry J Flores Lei Huang Xu Luo Xingyu Zhang Zongyi Zhang Ruihao Li Lingui Gu Siyuan Dong Shiyi Zhu Kun Yi Mingyang Han Lei Wu You Zhou John H Zhang Zongyi Xie Jiping Tang Source Type: research
Exploring new horizons: Emerging therapeutic strategies for pediatric stroke
Exp Neurol. 2024 Jan 24;374:114701. doi: 10.1016/j.expneurol.2024.114701. Online ahead of print.ABSTRACTPediatric stroke presents unique challenges, and optimizing treatment strategies is essential for improving outcomes in this vulnerable population. This review aims to provide an overview of new, innovative, and potential treatments for pediatric stroke, with a primary objective to stimulate further research in this field. Our review highlights several promising approaches in the realm of pediatric stroke management, including but not limited to stem cell therapy and robotic rehabilitation. These innovative interventions...
Source: Experimental Neurology - January 26, 2024 Category: Neurology Authors: Barbara Buccilli Source Type: research
Combining physical & amp; cognitive training with iPSC-derived dopaminergic neuron transplantation promotes graft integration & amp; better functional outcome in parkinsonian marmosets
This study suggests that integrating PCT with cell transplantation therapy could promote optimal graft functional integration and better outcome for patients with PD.PMID:38272159 | DOI:10.1016/j.expneurol.2024.114694 (Source: Experimental Neurology)
Source: Experimental Neurology - January 25, 2024 Category: Neurology Authors: Etienne W Daadi Elyas S Daadi Thomas Oh Mingfeng Li Jeffrey Kim Marcel M Daadi Source Type: research
Incomplete accumulation of perilesional reactive astrocytes exacerbates wound healing after closed-head injury by increasing inflammation and BBB disruption
Exp Neurol. 2024 Jan 23;374:114700. doi: 10.1016/j.expneurol.2024.114700. Online ahead of print.ABSTRACTWound healing after closed-head injury is a significant medical issue. However, conventional models of focal traumatic brain injury, such as fluid percussion injury and controlled cortical impact, employ mechanical impacts on the exposed cerebral cortex after craniotomy. These animal models are inappropriate for studying gliosis, as craniotomy itself induces gliosis. To address this, we developed a closed-head injury model and named "photo injury", which employs intense light illumination through a thinned-skull cranial ...
Source: Experimental Neurology - January 25, 2024 Category: Neurology Authors: Nitin Sawant Airi Watanabe Haruna Ueda Hideyuki Okano Mitsuhiro Morita Source Type: research
Dietary NMN supplementation enhances motor and NMJ function in ALS
Exp Neurol. 2024 Jan 22;374:114698. doi: 10.1016/j.expneurol.2024.114698. Online ahead of print.ABSTRACTAmyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that causes the degeneration of motor neurons in the motor cortex and spinal cord. Patients with ALS experience muscle weakness and atrophy in the limbs which eventually leads to paralysis and death. NAD+ is critical for energy metabolism, such as glycolysis and oxidative phosphorylation, but is also involved in non-metabolic cellular reactions. In the current study, we determined whether the supplementation of nicotinamide mononucleotide (NM...
Source: Experimental Neurology - January 24, 2024 Category: Neurology Authors: Samuel Lundt Nannan Zhang Luis Polo-Parada Xinglong Wang Shinghua Ding Source Type: research
Integrated network pharmacology, molecular docking and pharmacodynamic study reveals protective effects and mechanisms of corilagin against cerebral ischemia-induced injury
CONCLUSIONS: These results indicate that the molecular mechanism of the anti-ischemic effect of corilagin involves inhibiting neuronal apoptosis and activating the PI3K/Akt signaling pathway. These findings provide a theoretical and experimental basis for the further development and application of corilagin as a potential anti-ischemic stroke agent.PMID:38266765 | DOI:10.1016/j.expneurol.2024.114697 (Source: Experimental Neurology)
Source: Experimental Neurology - January 24, 2024 Category: Neurology Authors: Daiju Tao Xin Xia Xiaochao Zhang Renhua Yang Yuan Yang Li Zhang Yunke Shi Di Lv Peng Chen Bo He Zhiqiang Shen Source Type: research
Transcriptomic dynamics governing serotonergic dysregulation in the dorsal raphe nucleus following mild traumatic brain injury
Exp Neurol. 2024 Jan 19;374:114695. doi: 10.1016/j.expneurol.2024.114695. Online ahead of print.ABSTRACTMild traumatic brain injury (mTBI) is a leading cause of disability in the United States, with neuropsychiatric disturbances such as depression, anxiety, PTSD, and social disturbances being common comorbidities following injury. The molecular mechanisms driving neuropsychiatric complications following neurotrauma are not well understood and current FDA-approved pharmacotherapies employed to ameliorate these comorbidities lack desired efficacy. Concerted efforts to understand the molecular mechanisms of and identify novel...
Source: Experimental Neurology - January 21, 2024 Category: Neurology Authors: Christopher J O'Connell Evan L Reeder Jacob A Hymore Ryan S Brown Gabrielle A Notorgiacomo Sean M Collins Gary A Gudelsky Matthew J Robson Source Type: research
Ischemic and hemorrhagic stroke lesion environments differentially alter the glia repair potential of neural progenitor cell and immature astrocyte grafts
Exp Neurol. 2024 Jan 18;374:114692. doi: 10.1016/j.expneurol.2024.114692. Online ahead of print.ABSTRACTUsing cell grafting to direct glia-based repair mechanisms in adult CNS injuries represents a potential therapeutic strategy for supporting functional neural parenchymal repair. However, glia repair directed by neural progenitor cell (NPC) grafts is dramatically altered by increasing lesion size, severity, and mode of injury. To address this, we studied the interplay between astrocyte differentiation and cell proliferation of NPC in vitro to generate proliferating immature astrocytes (ImA) using hysteretic conditioning. ...
Source: Experimental Neurology - January 20, 2024 Category: Neurology Authors: Honour O Adewumi Gabriela I Berniac Emily A McCarthy Timothy M O'Shea Source Type: research
Mild repetitive TBI reduces brain-derived neurotrophic factor (BDNF) in the substantia nigra and hippocampus: A preclinical model for testing BDNF-targeted therapeutics
This study provides an opportunity to investigate the mechanism of BDNF reduction in rodent models and provides a reliable paradigm to test BDNF-targeted therapeutics for the treatment of ND.PMID:38244886 | DOI:10.1016/j.expneurol.2024.114696 (Source: Experimental Neurology)
Source: Experimental Neurology - January 20, 2024 Category: Neurology Authors: Anisha A DSouza Praveen Kulkarni Craig F Ferris Mansoor M Amiji Benjamin S Bleier Source Type: research
Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson's disease progression
Exp Neurol. 2024 Jan 17;374:114693. doi: 10.1016/j.expneurol.2024.114693. Online ahead of print.ABSTRACTDopamine neurons in the substantia nigra pars compacta (SNc) synthesize and release dopamine, a critical neurotransmitter for movement and learning. SNc dopamine neurons degenerate in Parkinson's Disease (PD), causing a host of motor and non-motor symptoms. Here, we review recent conceptual advances in our basic understanding of the dopamine system - including our rapidly advancing knowledge of dopamine neuron heterogeneity - with special attention to their importance for understanding PD. In PD patients, dopamine neuron...
Source: Experimental Neurology - January 19, 2024 Category: Neurology Authors: Jillian L Seiler Xiaowen Zhuang Alexandra B Nelson Talia N Lerner Source Type: research
Metabotropic glutamate receptor 5 promotes blood-brain barrier recovery after traumatic brain injury
Exp Neurol. 2024 Jan 14;374:114691. doi: 10.1016/j.expneurol.2024.114691. Online ahead of print.ABSTRACTBlood-brain barrier (BBB) impairment and glutamate release are two pathophysiological features of traumatic brain injury (TBI), contributing to secondary brain damage and neuroinflammation. However, our knowledge of BBB integrity damage and dysfunction are still limited due to the diverse and fluctuating expression of glutamate receptors after trauma. Here, we confirmed the downregulation of metabotropic glutamate receptor 5 (mGluR5) on microvascular endothelial cell within the acute phase of TBI, and the recovered mGluR...
Source: Experimental Neurology - January 15, 2024 Category: Neurology Authors: Jiakui Ren Teng Yang Heting Liu Pengjiao Ma Mi Zhou Jiabo Li Tao Li Jianbin Sun Wenhui He Lunshan Xu Shuang-Shuang Dai Yang-Wuyue Liu Source Type: research
