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https://read.qxmd.com/read/30763060/identifying-new-amp-activated-protein-kinase-inhibitors-that-protect-against-ischemic-brain-injury
#1
Jae-Won Eom, Tae-Youn Kim, Bo-Ra Seo, Hwangseo Park, Jae-Young Koh, Yang-Hee Kim
We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc neurotoxicity representing at least one mechanism of ischemic neuronal death. Inhibition of AMPK could be a viable therapeutic strategy to prevent ischemic brain injury following stroke. This prompted our search for novel inhibitors of AMPK activity and zinc-induced neuronal death using cultured mouse cortex and a rat model of brain injury after middle cerebral artery occlusion (MCAO)...
February 14, 2019: ACS Chemical Neuroscience
https://read.qxmd.com/read/30762917/effect-of-oxidative-stress-in-rostral-ventrolateral-medulla-on-sympathetic-hyperactivity-after-traumatic-brain-injury
#2
Jigang Chen, Wen Chen, Kaiwei Han, Enbo Qi, Rongbin Chen, Minkun Yu, Lijun Hou, Liquan Lv
Sympathetic hyperactivity occurs in a subgroup of patients after traumatic brain injury (TBI). The rostral ventrolateral medulla (RVLM) is a key region for the activity of sympathetic nervous system. Oxidative stress in the RVLM is proved to be responsible for the increased level of sympathetic activity in animal models of hypertension and heart failure. In this study, we investigated whether oxidative stress in the RVLM contributed to the development of sympathetic hyperactivity after TBI in rats. Model of diffuse axonal injury was induced using Sprague-Dawley rats, and level of mean arterial pressure (MAP) and plasma Norepinephrine (NE) was measured to evaluate the sympathetic activity...
February 14, 2019: European Journal of Neuroscience
https://read.qxmd.com/read/30762013/neuroprotection-mediated-by-the-wnt-frizzled-signaling-pathway-in-early-brain-injury-induced-by-subarachnoid-hemorrhage
#3
Yang Wang, De-Jun Bao, Bin Xu, Chuan-Dong Cheng, Yong-Fei Dong, Xiang-Pin Wei, Chao-Shi Niu
The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern...
June 2019: Neural Regeneration Research
https://read.qxmd.com/read/30760300/therapeutic-hypercapnia-reduces-blood-brain-barrier-damage-possibly-via-protein-kinase-c%C3%AE%C2%B5-in-rats-with-lateral-fluid-percussion-injury
#4
Wan-Chao Yang, Qi Wang, Lai-Ting Chi, Yue-Zhen Wang, Hong-Ling Cao, Wen-Zhi Li
BACKGROUND: This study investigated whether therapeutic hypercapnia (TH) ameliorated blood-brain barrier (BBB) damage and improved the neurologic outcome in a rat model of lateral fluid percussion injury (FPI), and explored the possible underlying mechanism. METHODS: Rats underwent lateral FPI and received inhalation of 30%O2 -70%N2 or 30%O2 -N2 plus CO2 to maintain arterial blood CO2 tension (PaCO2 ) between 80 and 100 mmHg for 3 h. To further explore the possible mechanisms for the protective effects of TH, a PKC inhibitor staurosporine or PKCαβ inhibitor GÖ6976 was administered via intracerebral ventricular injection...
February 13, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30759298/renal-effects-of-exendin-4-in-an-animal-model-of-brain-death
#5
Natália Emerim Lemos, Cristine Dieter, Rodrigo Carlessi, Jakeline Rheinheimer, Letícia de Almeida Brondani, Cristiane Bauermann Leitão, Andrea Carla Bauer, Daisy Crispim
Organ transplantation is the gold standard therapy for the majority of patients with terminal organ failure. However, it is still a limited treatment especially due to the low number of brain death (BD) donors in relation to the number of waiting list recipients. Strategies to increase the quantity and quality of donor organs have been studied, and the administration of exendin-4 (Ex-4) to the donor may be a promising approach. Male Wistar rats were randomized into 3 groups: (1) control, without central nervous system injury; (2) BD induced experimentally, and (3) BD induced experimentally + Ex-4 administered immediately after BD induction...
February 13, 2019: Molecular Biology Reports
https://read.qxmd.com/read/30758811/osteopontin-counters-human-immunodeficiency-virus-type-1-induced-impairment-of-neurite-growth-through-mammalian-target-of-rapamycin-and-beta-integrin-signaling-pathways
#6
Mathilde Calvez, George Hseeh, Simon Benzer, Amanda M Brown
Despite the fact that human immunodeficiency virus type 1 (HIV-1) does not enter or replicate in neurons, its infection of a subset of resident brain glia cells (microglia and astrocytes) induces via disparate mechanisms, dysregulation of glutamate metabolism, neurotoxicity, and inflammation. Antiretroviral therapies suppress viral load, but cellular activation and release of proinflammatory factors, some of which is likely related to viral reservoirs, continue to promote a microenvironment that is injurious to neurons...
February 13, 2019: Journal of Neurovirology
https://read.qxmd.com/read/30754031/decoding-neural-activity-to-predict-rat-locomotion-using-intracortical-and-epidural-arrays
#7
Filipe O Barroso, Bryan Yoder, David Tentler, Josephine Wallner, Amina Kinkhabwala, Maria K Jantz, Robert D Flint, Pablo Tostado, Evonne Pei, Ambika Satish, Sarah Brodnick, Aaron Suminski, Justin C Williams, Lee E Miller, Matthew Tresch
OBJECTIVE: Recovery of voluntary gait after spinal cord injury (SCI) requires the restoration of effective motor cortical commands, either by means of a mechanical connection to the limbs, or by restored functional connections to muscles. The latter approach might use functional electrical stimulation (FES), driven by cortical activity, to restore voluntary movements. Moreover, there is evidence that this peripheral stimulation, synchronized with patients' voluntary effort, can strengthen descending projections and recovery...
February 12, 2019: Journal of Neural Engineering
https://read.qxmd.com/read/30753912/fastigial-nucleus-electrostimulation-promotes-axonal-regeneration-after-experimental-stroke-via-camp-pka-pathway
#8
An-Rong Wang, Ming-Zhe Hu, Zhi-Lei Zhang, Ze-Yu Zhao, Yan-Bin Li, Bin Liu
Axon regeneration after cerebral ischemia in mammals is inadequate to restore function, illustrating the need to design better strategies for improving outcomes. Improvement of axon regeneration has been achieved through fastigial nucleus electrostimulation (FNS) in animal researches. However, the mechanisms underlying this neuroprotection remain poorly understood. Increasing the levels of the second messenger cyclic AMP (cAMP) enhances axon regeneration, making it an excellent candidate molecule that has therapeutic potential...
February 9, 2019: Neuroscience Letters
https://read.qxmd.com/read/30747210/mir%C3%A2-335-promotes-stress-granule-formation-to-inhibit-apoptosis-by-targeting-rock2-in-acute-ischemic-stroke
#9
Wenwen Si, Shanyu Ye, Zhenxing Ren, Xin Liu, Zimei Wu, Yi Li, Jianhong Zhou, Saixia Zhang, Yiwei Li, Rudong Deng, Dongfeng Chen
Under harmful environmental conditions, stress granules (SGs), macromolecular aggregates that are associated with cell survival and death, are produced in the eukaryotic cytoplasm. However, whether and how microRNAs (miRNAs/miRs) modulate SG formation induced by acute ischemic stroke has not been investigated. In the present study, a rat model of middle cerebral artery occlusion (MCAO) was utilized and miRNA array profiling and reverse transcription‑quantitative polymerase chain reaction were performed. The results revealed that miR‑335 was downregulated during acute ischemic stroke, which was concomitant with reduced SG formation, enhanced apoptosis levels and increased Rho associated protein kinase 2 (ROCK2) expression...
January 22, 2019: International Journal of Molecular Medicine
https://read.qxmd.com/read/30746753/pre-injury-monocyte-macrophage-depletion-results-in-increased-blood-brain-barrier-permeability-after-traumatic-brain-injury
#10
Benjamin M Aertker, Akshita Kumar, Karthik S Prabhakara, Philippa Smith, Naama E Toledano Furman, Xue Hasen, Charles S Cox, Supinder S Bedi
Traumatic brain injury (TBI) effects both the brain and the immune system. Circulating monocytes/macrophages (Mo /Ma ) after a TBI may play an important role in preserving the blood-brain barrier (BBB), reducing brain edema, and interacting with resident microglia. To elucidate the role of circulating Mo /Ma , we utilized a monocyte/macrophage depletion model in response to TBI in male rats. Clodronate liposomes (CL) were used to deplete circulating Mo /Ma . A controlled cortical impact (CCI) injury model was used to create a TBI...
February 12, 2019: Journal of Neuroscience Research
https://read.qxmd.com/read/30745569/fetal-inflammation-is-associated-with-persistent-systemic-and-hippocampal-inflammation-and-dysregulation-of-hippocampal-glutamatergic-homeostasis
#11
Tate Gisslen, Garima Singh, Michael K Georgieff
BACKGROUND: Inflammation is a major cause of preterm birth and often results in a fetal inflammatory response syndrome (FIRS). Preterm infants with FIRS have a higher childhood incidence of neurodevelopmental disability than preterm infants without FIRS. The mechanisms connecting FIRS to neurodevelopmental disability in formerly preterm infants are not fully understood, but the effect on premature gray matter may have an important role. METHODS: Fetal rats were exposed to intra-amniotic (i...
February 11, 2019: Pediatric Research
https://read.qxmd.com/read/30742861/delayed-creatine-supplementation-counteracts-reduction-of-gabaergic-function-and-protects-against-seizures-susceptibility-after-traumatic-brain-injury-in-rats
#12
Rogerio R Gerbatin, Luiz Fernando Almeida Silva, Maurício S Hoffmann, Iuri D Della-Pace, Patricia Severo do Nascimento, Aline Kegler, Viviane Nogueira de Zorzi, Jane Marçal Cunha, Priscilla Botelho, João Bento Torres Neto, Ana Flavia Furian, Mauro Schneider Oliveira, Michele R Fighera, Luiz Fernando Freire Royes
Traumatic brain injury (TBI) is a devastating disease frequently followed by behavioral disabilities including post-traumatic epilepsy (PTE). Although reasonable progress in understanding its pathophysiology has been made, treatment of PTE is still limited. Several studies have shown the neuroprotective effect of creatine in different models of brain pathology, but its effects on PTE is not elucidated. Thus, we decided to investigate the impact of delayed and chronic creatine supplementation on susceptibility to epileptic seizures evoked by pentylenetetrazol (PTZ) after TBI...
February 8, 2019: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://read.qxmd.com/read/30742808/gastrodin-pretreatment-alleviates-rat-brain-injury-caused-by-cerebral-ischemic-reperfusion
#13
Shi-Peng Li, Li-Gong Bian, Xi-Yue Fu, Qing-Long Ai, Yue Sui, Ai-Dan Zhang, Hui-Qing Gao, Lian-Mei Zhong, Di Lu
Brain damage, including blood-brain barrier (BBB) dysfunction, neurological behavior deficit, cerebral infarction and inflammation, is commonly caused by ischemic-reperfusion (I/R) injury. Prevention of the above biological process defects is considered beneficial for patient recovery after I/R injury. This study was aimed to assess the neuroprotective effect of Gastrodin (GAS), an herbal agent, in experimentally induced cerebral ischemia. Sprague-Dawley adult rats were randomly divided into six groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, GAS (50, 100, and 200 mg/kg) pretreatment + MCAO groups (GAS) and Nimodipine (NIM) + MCAO, namely, the NIM group...
February 8, 2019: Brain Research
https://read.qxmd.com/read/30741784/the-gap-junction-inhibitor-ini-0602-attenuates-mechanical-allodynia-and-depression-like-behaviors-induced-by-spared-nerve-injury-in-rats
#14
Xiao-Min Zhang, Ling-Zhi Wang, Bo He, Yu-Ke Xiang, Li-Xia Fan, Qin Wang, Liang Tao
Gap junctions (GJs) are novel molecular targets for pain therapeutics due to their pain-promoting function. INI-0602, a new GJ inhibitor, exerts a neuroprotective role, while its role in neuropathic pain is unclear. The objective was to investigate the analgesic role and mechanisms of INI-0602 in neuropathic pain induced by spared nerve injury (SNI), and whether INI-0602 attenuated pain-induced depression-like behaviors. Rats were randomly assigned to saline treatment groups (sham+NS and SNI+NS) or INI-0602 treatment groups (sham+INI-0602 and SNI+INI-0602)...
February 7, 2019: Neuroreport
https://read.qxmd.com/read/30739499/brain-targeted-glycyrrhizic-acid-loaded-surface-decorated-nanoparticles-for-treatment-of-cerebral-ischaemia-and-its-toxicity-assessment
#15
Niyaz Ahmad, Abeer M Al-Subaiec, Rizwan Ahmad, Sonali Sharma, Md Aftab Alam, Mohammad Ashafaq, Rehan Abdur Rub, Farhan Jalees Ahmad
OBJECTIVE: Enhancement of CS-GA-PCL-NPs (Glycyrrhizic Acid-encapsulated-chitosan-coated-PCL-Nanoparticles) bioavailability in brain. METHODS: Double emulsification solvent evaporation method in order to develop CS-PCL-NPs (Chitosan-coated-PCL-Nanoparticles) followed by characterization of particle size and distribution, zeta potential, encapsulation efficiency and drug release (in vitro). To determine drug-uptake and its pharmacokinetic profile in brain as well as plasma, UHPLC (triple quadrupole Q-trap) MS/MS method was developed and optimized for CS-GA-PCL-NPs as well as to follow-up examined effective role of optimized NPs in reduction of all brain injury parameters after MCAO through the grip strength, locomotor activity, inflammatory cytokines levels, measurement of infarction volume and histopathological changes in neurons with safety/toxicity after i...
December 2019: Artificial Cells, Nanomedicine, and Biotechnology
https://read.qxmd.com/read/30738025/cerebral-18-f-fdg-metabolism-alteration-in-a-neuropathic-pain-model-following-brachial-plexus-avulsion-a-pet-ct-study-in-rats
#16
Jun Shen, Bei-Bei Huo, Xu-Yun Hua, Mou-Xiong Zheng, Ye-Chen Lu, Jia-Jia Wu, Chun-Lei Shan, Jian-Guang Xu
The present study aimed to investigate cerebral metabolic changes in a neuropathic pain model following deafferentation. A total of 24 Sprague-Dawley rats were included for modeling of right brachial plexus avulsion (BPA) through the posterior approach. As nerve injury would cause central sensitization and facilitate pain sensitivity in other parts of the body, thermal withdrawal latency (TWL) of the intact forepaw was assessed to investigate the level of pain perception following BPA-induced neuropathic pain...
February 6, 2019: Brain Research
https://read.qxmd.com/read/30736791/the-role-of-microglial-inflammasome-activation-in-pyroptotic-cell-death-following-penetrating-traumatic-brain-injury
#17
Stephanie W Lee, Juan Pablo de Rivero Vaccari, Jessie S Truettner, W Dalton Dietrich, Robert W Keane
BACKGROUND: Traumatic brain injury remains a significant cause of death and disability in the USA. Currently, there are no effective therapies to mitigate disability except for surgical interventions necessitating a need for continued research into uncovering novel therapeutic targets. In a recent study, we used a rodent model of penetrating traumatic brain injury known as penetrating ballistic-like brain injury (PBBI) to examine the role of innate immunity in post-traumatic secondary injury mechanisms...
February 8, 2019: Journal of Neuroinflammation
https://read.qxmd.com/read/30735877/time-dependent-bi-directional-neuroprotection-by-adenosine-2a-receptor-in-experimental-traumatic-brain-injury
#18
Parthiban Velayutham, Muthukumar Murthy, Krothapalli Srinivasa Babu
BACKGROUND: Traumatic Brain Injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated severely after initial injury. Due to this disease complexity in nature, there is still no effective therapeutic measure aimed directly at these pathological processes. We developed a clinically relevant model of TBI and tested bidirectional neuroprotective role of adenosine 2A receptors (A2AR) at different time window periods. METHODS: Animals (Wistar Rats) were divided into four treatment groups- Sham, TBI, A2AR agonist (CGS-21680) and A2AR antagonist (SCH-58261) with four post TBI time windows (15mins, 1, 12 and 24hrs)...
February 5, 2019: World Neurosurgery
https://read.qxmd.com/read/30723838/effects-of-subanesthetic-intravenous-ketamine-infusion-on-neuroplasticity-related-proteins-in-the-prefrontal-cortex-amygdala-and-hippocampus-of-sprague-dawley-rats
#19
Michael Zhang, Kennett D Radford, Mercedes Driscoll, Salsabila Purnomo, Jean Kim, Kwang H Choi
Ketamine, a multimodal dissociative anesthetic, is a powerful analgesic administered following trauma due to its hemodynamic and respiratory stability. However, ketamine can cause hallucination and dissociation which may adversely impact traumatic memory after an injury. The effects of ketamine on proteins implicated in neural plasticity are unclear due to different doses, routes, and timing of drug administration in previous studies. Here, we investigated the effects of a single intravenous (IV) ketamine infusion on protein levels in three brain regions of rats...
June 2019: IBRO Reports
https://read.qxmd.com/read/30720182/downregulation-of-microrna-196a-attenuates-ischemic-brain-injury-in-rats-by-directly-targeting-hmga1
#20
D-L Zhang, X Liu, Q Wang, N Li, S-H Wu, C Wang
OBJECTIVE: Dysfunction of the microRNA (miRNA) network is a major regulator in neurological diseases. However, little is known about the functional significance of miRs in ischemic brain injury. This study was designed to investigate the functional behaviors and regulatory mechanisms of miR-196a in ischemic brain injury. MATERIALS AND METHODS: Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. The expression levels of miR-196a and HMGA1 were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blotting, and/or immunocytochemistry...
January 2019: European Review for Medical and Pharmacological Sciences
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