Dataset Information

'Hit & Run' model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation.

ABSTRACT: Cerebral edema is a major contributor to morbidity associated with traumatic brain injury (TBI). The methods involved in most rodent models of TBI, including head fixation, opening of the skull, and prolonged anesthesia, likely alter TBI development and reduce secondary injury. We report the development of a closed-skull model of murine TBI, which minimizes time of anesthesia, allows the monitoring of intracranial pressure (ICP), and can be modulated to produce mild and moderate grade TBI. In this model, we characterized changes in aquaporin-4 (AQP4) expression and localization after mild and moderate TBI. We found that global AQP4 expression after TBI was generally increased; however, analysis of AQP4 localization revealed that the most prominent effect of TBI on AQP4 was the loss of polarized localization at endfoot processes of reactive astrocytes. This AQP4 dysregulation peaked at 7 days after injury and was largely indistinguishable between mild and moderate grade TBI for the first 2 weeks after injury. Within the same model, blood-brain barrieranalysis of variance permeability, cerebral edema, and ICP largely normalized within 7 days after moderate TBI. These findings suggest that changes in AQP4 expression and localization may not contribute to cerebral edema formation, but rather may represent a compensatory mechanism to facilitate its resolution.

SUBMITTER: Ren Z

PROVIDER: S-EPMC3677112 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

'Hit & Run' model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation.

Ren Zeguang Z Iliff Jeffrey J JJ Yang Lijun L Yang Jiankai J Chen Xiaolin X Chen Michael J MJ Giese Rebecca N RN Wang Baozhi B Shi Xuefang X Nedergaard Maiken M

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20130227 6

Cerebral edema is a major contributor to morbidity associated with traumatic brain injury (TBI). The methods involved in most rodent models of TBI, including head fixation, opening of the skull, and prolonged anesthesia, likely alter TBI development and reduce secondary injury. We report the development of a closed-skull model of murine TBI, which minimizes time of anesthesia, allows the monitoring of intracranial pressure (ICP), and can be modulated to produce mild and moderate grade TBI. In th ...[more]

PMID: 23443171

Similar Datasets

Project description:BackgroundDynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking.ResultsHere, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run").ConclusionOur findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

Project description:Some parasites of social insects are able to exploit the exchange of food between nestmates via trophallaxis, because they are chemically disguised as nestmates. However, a few parasites succeed in trophallactic solicitation although they are attacked by workers. The underlying mechanisms are not well understood. The small hive beetle (=SHB), Aethina tumida, is such a parasite of honey bee, Apis mellifera, colonies and is able to induce trophallaxis. Here, we investigate whether SHB trophallactic solicitation is innate and affected by sex and experience. We quantified characteristics of the trophallactic solicitation in SHBs from laboratory-reared individuals that were either bee-naïve or had 5 days experience. The data clearly show that SHB trophallactic solicitation is innate and further suggest that it can be influenced by both experience and sex. Inexperienced SHB males begged more often than any of the other groups had longer breaks than their experienced counterparts and a longer soliciting duration than both experienced SHB males and females, suggesting that they start rather slowly and gain more from experience. Successful experienced females and males were not significantly different from each other in relation to successful trophallactic interactions, but had a significantly shorter soliciting duration compared to all other groups, except successful inexperienced females. Trophallactic solicitation success, feeding duration and begging duration were not significantly affected by either SHB sex or experience, supporting the notion that these behaviors are important for survival in host colonies. Overall, success seems to be governed by quality rather than quantity of interactions, thereby probably limiting both SHB energy investment and chance of injury (<1%). Trophallactic solicitation by SHBs is a singular example for an alternative strategy to exploit insect societies without requiring chemical disguise. Hit-and-run trophallaxis is an attractive test system to get an insight into trophallaxis in the social insects.

Project description:Background: Low and medium income countries (LMICs) such as Kenya experience nearly three times more cases of traumatic brain injury (TBI) compared to high income countries (HICs). This is primarily exacerbated by weak health systems especially at the pre-hospital care level. Generating local empirical evidence on TBI patterns and its influence on patient mortality outcomes is fundamental in informing the design of trauma-specific emergency medical service (EMS) interventions at the pre-hospital care level. This study determines the influence of TBI patterns and mortality. Methods: This was a case-control study with a sample of 316 TBI patients. Data was abstracted from medical records for the period of January 2017 to March 2019 in three tertiary trauma care facilities in Kenya. Logistic regression was used to assess influence of trauma patterns on TBI mortality, controlling for patient characteristics and other potential confounders. Results: The majority of patients were aged below 40 years (73%) and were male (85%). Road traffic injuries (RTIs) comprised 58% of all forms of trauma. Blunt trauma comprised 71% of the injuries. Trauma mechanism was the only trauma pattern significantly associated with TBI mortality. The risk of dying for patients sustaining RTIs was 2.83 times more likely compared to non-RTI patients [odds ratio (OR) 2.83, 95% confidence interval (CI) 1.62-4.93, p=0.001]. The type of transfer to hospital was also significantly associated with mortality outcome, with a public hospital having a two times higher risk of death compared to a private hospital [OR 2.18 95%CI 1.21-3.94, p<0.009]. Conclusion: Trauma mechanism (RTI vs non-RTI) and type of tertiary facility patients are transferred to (public vs private) are key factors influencing TBI mortality burden. Strengthening local EMS trauma response systems targeting RTIs augmented by adequately resourced and equipped public facilities to provide quality lifesaving interventions can reduce the burden of TBIs.

Dataset Information

'Hit & Run' model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation.

Publications

'Hit & Run' model of closed-skull traumatic brain injury (TBI) reveals complex patterns of post-traumatic AQP4 dysregulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets