Searching PROSPERO for Macrophages ...

In order to make sure there are no other Systematic Searches on the relationships between neuroinflammation, macrophages and neurodegeneration in progress, I ran a wide search in PROSPERO using all fields for each term which revealed only three articles and each not close to my area of interest.

Search stings used:

Resulting articles: 

Macrophages signal cytokine activation

One advantage of having to change topics slightly from a cytokine focus to Macrophages, is that the research is showing that macrophages seem to activate earlier than cytokines. Thus if the end goal is to find an early bio-marker for Parkinson's disease progression, the earlier the signal from neuroinflammation and neurodegeneration the better the chances of slowing or treating the damaging process.

Moving forward, I read a paper some time back by Perry (2004) "The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease",  in which he made mention of the role of macrophages as a key messenger in sickness behaviour. Further reading on macrophages indicated that these were instrumental in the triggering of neurodegeneration. 

The importance of macrophages was reinforced in a more recent paper by Blaylock (2017), "Parkinson's disease: Microglial and macrophage induced immunoexcitotoxicity as a central mechanism of neurodegeneration". Research by Blaylock suggests that macrophages must be fully activated in order to signal and activate cytokines such as TNF-alpha and IL-1B. In addition, they need to operate in unison with other signalling pathways such as the glutamate receptors in order to trigger excitatory responses, and that it is the combination of both macrophages and excitatory responses that creates the heightened activity that leads to increased cell death and neurodegeneration.

Systematic Review Title ...

Initial thoughts were to look at inflammation, particularly neuroinflammation and the resulting immune response - mainly cytokines & interleukin and their impact on subsequent cell death and triggering of neurodegenerative diseases such as Parkinson's disease.

The results from some of my preliminary database searches turned up a recent Systematic review:

 "Aberrations in Peripheral Inflammatory Cytokine Levels in Parkinson Disease: A Systematic Review and Meta-analysis", 2016, Qin et al.

Given that the above systematic search is very close to the one I was working on, I need to change my focus towards other blood based signalling mechanisms involved in the immune response.

Action items :

• How many articles have looked at macrophages?
• What other pathways do macrophages activate (excluding cytokines)?
• Have any of those downstream arms of the pathways been implicated?
• Look at articles citing Perry for guidance

Macrophages

Data Management for file selection

Data Management

     Once each of the search strategies are run, the following methodology will be used to collect the results and save each as individual files:

1.    Each selected database will be searched on title and abstract using the defined Search Strategy & Structure criteria outlined above. The initial raw results will then be saved to an XML file.

2.    Next the initial results will be filtered for both the inclusion and exclusion criteria outlined above, and the results will be saved to an XML file. Each of these steps will be repeated for all databases to be searched.

3.    Initial results and filtered results for inclusions and exclusions i.e. number of journals found for each database search will be recorded in line with the PRISMA 2009 Systematic review flow diagram requirements.

4.    Each XML result file will be uploaded into Covidence to assist in identifying duplicate articles. The number of duplicates will be recorded in the PRISMA flow diagram to adjust the available articles for systematic review.

5.    The resulting “cleaned” Covidence reference database journal numbers will be recorded in the PRISMA flow diagram.

6.    An email link will then be sent to three independent research academics suitably skilled to review and select appropriate journal articles for review. To ensure there is no research or selection bias, the selection of a successful article will require two out of three votes to be included for the systematic review.

7.    The final selection of journal articles will be exported as an XML file from Covidence and retained along with the raw and filtered search results from each of the five databases to support any future requests for information on the search methodology.

8.    The Covidence XML export of the final selection of journals will then be uploaded into Endnote v9 and read in full with information collected and analyzed for summary and discussion in the systematic review.

Systematic Search Strings ...

Based on the key words aken from potential target journal articles, I have developed four search strings for Inflammation, Neurodegeneration, Parkinson's disease and Blood.

Search Strategy & Structure:

Key terms used in the search strategy are:

1.  Inflamm(*) using a wild card to capture terms such as inflammation, inflammatory, neuroinflammatory

2.  Neurodegen(*) OR brain* OR “white matter” OR CNS OR “nervous system” OR neuron(*) OR dopamine(*) OR apopto(*) OR mitochond(*) using a wild card to capture terms such as neurodegeneration and neurodegenerative topics

3.  Parkinson(*) using a wild card to capture terms such as Parkinson’s disease, Parkinson’s and Parkinsonism

4. Blood(*) OR plasma OR serum OR haemoglob(*) OR "white blood cells" OR "red blood cells" OR leukocyte(*) OR peripheral(*)