LIVIVO - Search results -

Search results

Result 1 - 10 of total 18

Search options

Article ; Online: Time-Dependent Long-Term Effect of Memantine following Repetitive Mild Traumatic Brain Injury.

Boucher, Masen L / Conley, Grace / Morriss, Nicholas J / Ospina-Mora, Sara / Qiu, Jianhua / Mannix, Rebekah / Meehan, William P

Journal of neurotrauma

2024

Abstract: Repetitive mild traumatic brain injury (rmTBI, e.g., sports concussions) may be associated with both acute and chronic symptoms and neurological changes. Despite the common occurrence of these injuries, therapeutic strategies are limited. One potentially ...

Abstract	Repetitive mild traumatic brain injury (rmTBI, e.g., sports concussions) may be associated with both acute and chronic symptoms and neurological changes. Despite the common occurrence of these injuries, therapeutic strategies are limited. One potentially promising approach is N-methyl-D-aspartate receptor (NMDAR) blockade to alleviate the effects of post-injury glutamatergic excitotoxicity. Initial pre-clinical work using the NMDAR antagonist, memantine, suggests that immediate treatment following rmTBI improves a variety of acute outcomes. It remains unclear (1) whether acute memantine treatment has long-term benefits and (2) whether delayed treatment following rmTBI is beneficial, which are both clinically relevant concerns. To test this, animals were subjected to rmTBI via a weight drop model with rotational acceleration (five hits in 5 days) and randomized to memantine treatment immediately, 3 months, or 6 months post-injury, with a treatment duration of one month. Behavioral outcomes were assessed at 1, 4, and 7 months post-injury. Neuropathological outcomes were characterized at 7 months post-injury. We observed chronic changes in behavior (anxiety-like behavior, motor coordination, spatial learning, and memory), as well as neuroinflammation (microglia, astrocytes) and tau phosphorylation (T231). Memantine treatment, either immediately or 6 months post-injury, appears to confer greater rescue of neuroinflammatory changes (microglia) than vehicle or treatment at the 3-month time point. Although memantine is already being prescribed chronically to address persistent symptoms associated with rmTBI, this study represents the first evidence of which we are aware to suggest a small but durable effect of memantine treatment in mild, concussive injuries. This effect suggests that memantine, although potentially beneficial, is insufficient to treat all aspects of rmTBI alone and should be combined with other therapeutic agents in a multi-therapy approach, with attention given to the timing of treatment.
Language	English
Publishing date	2024-05-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2023.0423
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2016: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Optimizing Choice and Timing of Behavioral Outcome Tests After Repetitive Mild Traumatic Brain Injury: A Machine Learning-Based Approach on Multiple Pre-Clinical Experiments.

Lassarén, Philipp / Conley, Grace / Boucher, Masen L / Conley, Ashley N / Morriss, Nicholas J / Qiu, Jianhua / Mannix, Rebekah C / Thelin, Eric Peter

Journal of neurotrauma

2023 Volume 40, Issue 15-16, Page(s) 1762–1778

Abstract: Repetitive mild traumatic brain injury (rmTBI) is a potentially debilitating condition with long-term sequelae. Animal models are used to study rmTBI in a controlled environment, but there is currently no established standard battery of behavioral tests ... ...

Abstract	Repetitive mild traumatic brain injury (rmTBI) is a potentially debilitating condition with long-term sequelae. Animal models are used to study rmTBI in a controlled environment, but there is currently no established standard battery of behavioral tests used. Primarily, we aimed to identify the best combination and timing of behavioral tests to distinguish injured from uninjured animals in rmTBI studies, and secondarily, to determine whether combinations of independent experiments have better behavioral outcome prediction accuracy than individual experiments. Data from 1203 mice from 58 rmTBI experiments, some of which have already been published, were used. In total, 11 types of behavioral tests were measured by 37 parameters at 13 time points during the first 6 months after injury. Univariate regression analyses were used to identify optimal combinations of behavioral tests and whether the inclusion of multiple heterogenous experiments improved accuracy.
MeSH term(s)	Mice ; Animals ; Brain Concussion/diagnosis ; Brain Concussion/complications ; Maze Learning ; Models, Animal ; Behavior, Animal ; Disease Models, Animal
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2022.0486
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2016: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Titrating the Translational Relevance of a Low-Level Repetitive Head Impact Model.

Boucher, Masen L / Conley, Grace / Nowlin, Jordan / Qiu, Jianhua / Kawata, Keisuke / Bazarian, Jeffrey J / Meehan, William P / Mannix, Rebekah

Frontiers in neurology

2022 Volume 13, Page(s) 857654

Abstract: Recently, there has been increased attention in the scientific community to the phenomenon of sub-concussive impacts, those hits to the head that do not cause the signs and symptoms of a concussion. Some authors suggest that sub-concussive impacts may ... ...

Abstract	Recently, there has been increased attention in the scientific community to the phenomenon of sub-concussive impacts, those hits to the head that do not cause the signs and symptoms of a concussion. Some authors suggest that sub-concussive impacts may alter behavior and cognition, if sustained repetitively, but the mechanisms underlying these changes are not well-defined. Here, we adapt our well-established weight drop model of repetitive mild traumatic brain injury (rmTBI) to attempt to produce a model of low-level repetitive head impacts (RHI). The model was modified to eliminate differences in latency to right following impact and gross behavioral changes after a single cluster of hits. Further, we varied our model in terms of repetition of impact over a 4-h span to mimic the repeated sub-concussive impacts that may be experienced by an athlete within a single day of play. To understand the effects of a single cluster of RHIs, as well as the effect of an increased impact frequency within the cluster, we evaluated classical behavioral measures, serum biomarkers, cortical protein quantification, and immunohistochemistry both acutely and sub-acutely following the impacts. In the absence of gross behavioral changes, the impact protocol did generate pathology, in a dose-dependent fashion, in the brain. Evaluation of serum biomarkers revealed limited changes in GFAP and NF-L, which suggests that their diagnostic utility may not emerge until the exposure to low-level head impacts reaches a certain threshold. Robust decreases in both IL-1β and IL-6 were observed in the serum and the cortex, indicating downregulation of inflammatory pathways. These experiments yield initial data on pathology and biomarkers in a mouse model of low-level RHIs, with relevance to sports settings, providing a starting point for further exploration of the potential role of anti-inflammatory processes in low-level RHI outcomes, and how these markers may evolve with repeated exposure.
Language	English
Publishing date	2022-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.857654
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Traumatic Brain Injury-Related Optic Nerve Damage.

Qiu, Jianhua / Boucher, Masen / Conley, Grace / Li, Yue / Zhang, Jingdong / Morriss, Nicholas / Meehan Iii, William P / Mannix, Rebekah

Journal of neuropathology and experimental neurology

2022 Volume 81, Issue 5, Page(s) 344–355

Abstract: Vision disorders are associated with traumatic brain injury (TBI) in 20%-40% of clinical cases and involve a diverse set of potential symptoms that can present acutely or chronically. Due to its structure and position, the optic nerve is vulnerable to ... ...

Abstract	Vision disorders are associated with traumatic brain injury (TBI) in 20%-40% of clinical cases and involve a diverse set of potential symptoms that can present acutely or chronically. Due to its structure and position, the optic nerve is vulnerable to multiple forms of primary injury, which can result in traumatic optic neuropathy (TON). Multiple studies have shown that the optic tract may also be injured during TBI, though data regarding the temporospatial resolution of injury to the optic nerve are sparse. We evaluated the time course of optic nerve injury and visual impairments in our closed head impact acceleration mouse model of mild TBI (mTBI) designed to mimic repetitive injuries experienced in the context of sport. Our results show that inflammation and gliosis occur acutely in response to injury. Additionally, indications of optic nerve degeneration and functional loss of vision beginning at 1-month postinjury, and retinal ganglion cell loss at 7 months, revealed that the degeneration is continuous and permanent. Together, this study demonstrated that the optic nerve is vulnerable to damage during mTBI, which can cause TON and vision loss. These findings will be important for clinicians to consider to determine whether optic nerve is injured in the TBI patients with vision problems.
MeSH term(s)	Animals ; Brain Injuries ; Brain Injuries, Traumatic/complications ; Humans ; Mice ; Mice, Inbred C57BL ; Optic Nerve ; Optic Nerve Injuries/complications
Language	English
Publishing date	2022-04-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlac018
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.134: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Ui II Zs.194: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Evaluation of a rapid and automated heparin-induced thrombocytopenia immunoassay.

Refaai, Majed A / Conley, Grace / Ortel, Thomas L / Francis, John L

International journal of laboratory hematology

2019 Volume 41, Issue 4, Page(s) 478–484

Abstract: Introduction: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin. Laboratory evaluation of HIT is often not available within a reasonable time. We evaluated the HemosIL: Materials and methods: ... ...

Abstract	Introduction: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse reaction of heparin. Laboratory evaluation of HIT is often not available within a reasonable time. We evaluated the HemosIL Materials and methods: Following determination of the LIA's reference interval and cutoff values, a multicenter study was conducted between March 2013 and June 2015. Plasma samples of HIT-suspected patients (n = 632) were collected and evaluated by LIA on the ACL TOP Results: Based on the 95% reference interval for healthy donors and HIT-negative patients, a LIA value ≥1.0 U/mL was interpreted positive. The overall agreement of LIA versus EIA and SRA results were 90% (95% CI 88%-92%) and 79% (95% CI 75%-82%), respectively. The negative predictive value for LIA and EIA was comparable (87%) with SRA. The positive and negative percent agreements with the clinical probability were 89% (95% CI 69%-97%) and 86% (95% CI 83%-89%), respectively, with a negative predictive value of 99.6% (95% CI 98%-100%). Discussion: Overall, the LIA results were comparable to those of EIA and SRA. This fully automated assay with a remarkable short analytical turnaround time of <20 minutes can be performed on-demand, which would greatly facilitate more prompt management of HIT.
MeSH term(s)	Enzyme-Linked Immunosorbent Assay ; Female ; Heparin/administration & dosage ; Heparin/adverse effects ; Humans ; Male ; Middle Aged ; Serotonin/blood ; Thrombocytopenia/blood ; Thrombocytopenia/chemically induced ; Thrombocytopenia/diagnosis
Chemical Substances	Serotonin (333DO1RDJY) ; Heparin (9005-49-6)
Language	English
Publishing date	2019-04-15
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Multicenter Study
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.13029
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1499: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Mutation in the Bone Morphogenetic Protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations.

Klem, John R / Schwantes-An, Tae-Hwi / Abreu, Marco / Suttie, Michael / Gray, Raeden / Vo, Hieu / Conley, Grace / Foroud, Tatiana M / Wetherill, Leah / Lovely, C Ben

bioRxiv : the preprint server for biology

2023

Abstract: Fetal Alcohol Spectrum Disorders (FASD) describe ethanol-induced developmental defects including craniofacial malformations. While ethanol-sensitive genetic mutations contribute to facial malformations, the impacted cellular mechanisms remain unknown. ... ...

Abstract	Fetal Alcohol Spectrum Disorders (FASD) describe ethanol-induced developmental defects including craniofacial malformations. While ethanol-sensitive genetic mutations contribute to facial malformations, the impacted cellular mechanisms remain unknown. Bmp signaling is a key regulator of epithelial morphogenesis driving facial development, providing a possible ethanol-sensitive mechanism. We found that zebrafish mutants for Bmp signaling components are ethanol-sensitive and affect anterior pharyngeal endoderm shape and gene expression, indicating ethanol-induced malformations of the anterior pharyngeal endoderm cause facial malformations. Integrating FASD patient data, we provide the first evidence that variants in the human Bmp receptor gene BMPR1B associate with ethanol-related differences in jaw volume. Our results show that ethanol exposure disrupts proper morphogenesis of, and tissue interactions between, facial epithelia that mirror overall viscerocranial shape changes and are predictive for Bmp-ethanol associations in human jaw development. Our data provide a mechanistic paradigm linking ethanol to disrupted epithelial cell behaviors that underlie facial defects in FASD.
Language	English
Publishing date	2023-10-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.28.546932
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Automated Quantification of Immunohistochemical Staining of Large Animal Brain Tissue Using QuPath Software.

Morriss, Nicholas J / Conley, Grace M / Ospina, Sara M / Meehan Iii, William P / Qiu, Jianhua / Mannix, Rebekah

Neuroscience

2020 Volume 429, Page(s) 235–244

Abstract: Large scale unbiased quantification of immunohistochemistry (IHC) is time consuming, expensive, and/or limited in scope. Heterogeneous tissue types such as brain tissue have presented a further challenge to the development of automated analysis, as ... ...

Abstract	Large scale unbiased quantification of immunohistochemistry (IHC) is time consuming, expensive, and/or limited in scope. Heterogeneous tissue types such as brain tissue have presented a further challenge to the development of automated analysis, as differing cellular morphologies result in either limited applicability or require large amounts of training tissue for machine-learning methods. Here we present the use of QuPath, a free and open source software, to quantify whole-brain sections stained with the immunohistochemical markers IBA1 and AT8, for microglia and phosphorylated tau respectively. The pixel-based method of analysis herein allows for statistical comparison of global protein expression between brains and generates heat-maps of stain intensity, visualizing stain signal across whole sections and permitting more specific investigation of regions of interest. This method is fast, automated, unbiased, and easily replicable. We compared swine brains that had undergone a closed head traumatic brain injury with brains of sham animals, and found a global increase in both microglial signal expression and phosphorylated tau. We discuss the IHC methods necessary to utilize this analysis and provide detailed instruction on the use of QuPath in the pixel-based analysis of whole-slide images.
MeSH term(s)	Animals ; Brain ; Image Processing, Computer-Assisted ; Immunohistochemistry ; Software ; Staining and Labeling ; Swine
Language	English
Publishing date	2020-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2020.01.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1215: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Clinical Nurses' Perceptions of a Senior Capstone Dedicated Educational Unit.

Glynn, Donna M / Wendt, Judith / Russell, Bonnie / Conley, Grace / Hill, Patrick

Nursing education perspectives

2018 Volume 40, Issue 2, Page(s) 107–109

Abstract: Clinical nurses' perceptions of a senior capstone dedicated educational unit (DEU) model to transition to practice was evaluated in a pilot study. Nursing students were placed in the traditional capstone and the DEU senior capstone unit with clinical ... ...

Abstract	Clinical nurses' perceptions of a senior capstone dedicated educational unit (DEU) model to transition to practice was evaluated in a pilot study. Nursing students were placed in the traditional capstone and the DEU senior capstone unit with clinical nurses. Staff nurses completed an online survey to compare and contrast satisfaction and effectiveness of the models. The results of the study revealed no perceived differences in the outcomes of a DEU experience as compared to the traditional preceptor model. However, nursing management reported an improved sense of leadership and teamwork on the unit with the DEU model.
MeSH term(s)	Education, Nursing, Baccalaureate ; Humans ; Models, Educational ; Pilot Projects ; Students, Nursing
Language	English
Publishing date	2018-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2075410-3
ISSN	1943-4685 ; 1536-5026
ISSN (online)	1943-4685
ISSN	1536-5026
DOI	10.1097/01.NEP.0000000000000367
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3023: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Memantine Mitigates Oligodendrocyte Damage after Repetitive Mild Traumatic Brain Injury.

Ma, Guixian / Liu, Changyun / Hashim, Jumana / Conley, Grace / Morriss, Nicholas / Meehan, William P / Qiu, Jianhua / Mannix, Rebekah

Neuroscience

2019 Volume 421, Page(s) 152–161

Abstract: Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment, white matter injury and increased risk of neurodegeneration. Targeted therapies for rmTBI are lacking, though evidence ... ...

Abstract	Repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions) is common and results in significant cognitive impairment, white matter injury and increased risk of neurodegeneration. Targeted therapies for rmTBI are lacking, though evidence from other injury models indicates that targeting N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated glutamatergic toxicity might mitigate rmTBI-induced injury. We have previously shown that the NMDAR antagonist memantine lessens axonal injury and restores long term potentiation after rmTBI. Here, we evaluated whether the protective effects of memantine include oligodendrocyte specific mechanisms, as prior studies suggest that oligodendrocytes are particularly vulnerable to glutamatergic toxicity. Mice were subjected to rmTBI injury (5 injuries in 5 days) and randomized to treatment with memantine or with vehicle (n = 32/group). At the molecular level, oligodendrocyte counts and function (myelin basic protein, MBP) were assessed by immunohistochemistry and western blot at days 3, 7 and 28 days after the last injury. Axon integrity was assessed by neurofilament light chain (NF-l) expression and axonal ultrastructure was evaluated by electron microscopy. Compared to vehicle-treated mice, memantine-treated mice were protected against oligodendrocyte loss and decreased MBP expression at subacute time points after injury. Memantine treatment also protected against axon damage assessed by NF-l expression. These data suggest that the therapeutic effects of post-concussive NMDAR antagonism may in part work through oligodendrocyte specific mechanisms, which may have implications for long term neurodegenerative sequelae after multiple concussions.
MeSH term(s)	Animals ; Axons/metabolism ; Brain/drug effects ; Brain/metabolism ; Brain/physiopathology ; Brain Concussion/complications ; Brain Concussion/prevention & control ; Glycogen Synthase Kinase 3 beta/metabolism ; Male ; Memantine/pharmacology ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Myelin Basic Protein/metabolism ; Neurofilament Proteins/metabolism ; Oligodendroglia/drug effects ; Oligodendroglia/metabolism ; Oligodendroglia/pathology ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/metabolism
Chemical Substances	Mbp protein, mouse ; Myelin Basic Protein ; Neurofilament Proteins ; Receptors, N-Methyl-D-Aspartate ; neurofilament protein L ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, mouse (EC 2.7.11.1) ; Memantine (W8O17SJF3T)
Language	English
Publishing date	2019-11-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2019.10.016
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1215: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: BBB pathophysiology-independent delivery of siRNA in traumatic brain injury.

Li, Wen / Qiu, Jianhua / Li, Xiang-Ling / Aday, Sezin / Zhang, Jingdong / Conley, Grace / Xu, Jun / Joseph, John / Lan, Haoyue / Langer, Robert / Mannix, Rebekah / Karp, Jeffrey M / Joshi, Nitin

Science advances

2021 Volume 7, Issue 1

Abstract: Small interfering RNA (siRNA)-based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment ... ...

Abstract	Small interfering RNA (siRNA)-based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.
MeSH term(s)	Animals ; Blood-Brain Barrier ; Brain ; Brain Injuries, Traumatic/genetics ; Brain Injuries, Traumatic/therapy ; Mice ; Nanoparticles ; RNA, Small Interfering/genetics
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2021-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abd6889
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito