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Spinal Cord Injury Causes Chronic Liver Pathology in Rats

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

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Cai, S R; Motoyama, K; Shen, K J; Kennedy, S C; Flye, M W; Ponder, K P

Liver insufficiency occurs when the liver cannot perform critical functions such as ammonia metabolism, gluconeogenesis, or production of coagulation factors The hypothesis of this study was that decreased function of existing hepatocytes may contribute to hepatic failure, and that the function of these cells might be increased pharmacologically. Lovastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor that inhibits cholesterol biosynthesis and affects the activity of some signal transduction pathways and liver transcription factors. Changes in hepatic transcription factors during liver regeneration might result in decreased liver functions, and lovastatin might prevent these changes Rats received 90% partial hepatectomy (90% PH), and either lovastatin or vehicle alone daily. Survival and liver functions were assessed. Lovastatin increased survival to 58% (vs. 6% in controls that received 90% PH without drug), decreased the peak ammonia level to 427 microM (vs. 846 microM in controls), increased the nadir of glucose to 88 mg/dl (vs. 57 mg/dl in controls), decreased the peak prothrombin time to 23 s (vs 29 s in controls), and decreased the peak activated partial thromboplastin time to 29 s (vs. 39 s in controls). The full survival and metabolic benefits were observed when lovastatin was started at 30 min after 90% PH, but lovastatin was less efficacious when started at later times. Lovastatin increases the function of existing hepatocytes and might be used to improve liver function after extensive hepatic resection.

React Navigation (v2)

Warning: in the next major version of React Navigation, to be released in Fall 2018, we will no longer provide any information about how to integrate with Redux and it may cease to work . Issues related to Redux that are posted on the React Navigation issue tracker will be immediately closed. Redux integration may continue to work but it will not be tested against or considered when making any design decisions for the library.

Some folks like to have their navigation state stored in the same place as the rest of their application state. . Storing your React Navigation state in your own Redux store is likely to give you a very difficult time if you don't know what you're doing.

If your only reason for doing this is that you want to be able to perform navigation actions from outside of your components (eg: from a Redux middleware), you can learn more about this in navigating without the navigation prop .


Step-by-step guide

The following steps apply to and .

First, you need to add the package to your project.


The following is a minimal example of how you might use navigators within a Redux application:

Once you do this, your navigation state is stored within your Redux store, at which point you can fire navigation actions using your Redux dispatch function.

Keep in mind that when a navigator is given a prop, it relinquishes control of its internal state. That means you are now responsible for persisting its state, handling any deep linking, Handling the Hardware Back Button in Android , etc.

Navigation state is automatically passed down from one navigator to another when you nest them. Note that in order for a child navigator to receive the state from a parent navigator, it should be defined as a .

Applying this to the example above, you could instead define to contain a nested as follows:

In this case, once you to Redux as is done in , will automatically have access to navigation state as a prop.

Full example

There's a working example app with Redux if you want to try it out yourself.

Mocking tests

To make jest tests work with your React Navigation app, you need to change the jest preset in the , see :

Under the hood

Creating your own navigation reducer

If you want to replace reducer creator this is how you would do it yourself:

Handling the Hardware Back Button in Android

By using the following snippet, your nav component will be aware of the back button press actions and will correctly interact with your stack. This is really useful on Android.

To handle your app's navigation state in Redux, you can pass your own prop to a navigator. handles this for you behind the scenes with a "higher-order component" called . You pass in your root navigator component to the function, and it returns a new component that takes your navigation and function as props.


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