"...on being inclusive ..."

It is easily understood that when reviewing the search results that we want to be focused on the main articles so the end result are manageable.

However I am puzzled by two things that I am having trouble reconciling:

1. You suggest a final target of around 100 articles. However, in the area of mitochondria there are many articles written every day and so the likelihood of getting around 80-100 articles will be tough and will require quite restrictive exclusion criteria I think.
2. With tight inclusion & exclusion criteria we will be knocking out a lot of documents that could contain some relevance to the research topic. Granted the whole article is not on the topic but there may be very significant sections. Why would we exclude such an article?

I am still wrapping my mind around how to combine each of the key words in my topic and to find something that registers as a systematic component.

In my topic discussion I have focused on using the search strategies discussed in my earlier posts and the relevant results to draft up as much of the methods section and results flow diagram as possible. If I then draft up a narrative around the temporal flow and the key connections this will allow us to focus more accurately on a draft rather than talking about a proposed theme in broad terms. With the draft we can see what its strengths and weaknesses are and then look to see how we extend it to define and incorporate the systematic section which hopefully can include something we can measure.

In terms of the measurement it would be ideal to have the preamble discuss how inflammation triggers the immune response and that microglia once activated can become chronic leading to significant mitochondrial damage and subsequently being associated with neuronal damage and cell apoptosis. One measure of this could be finding experimental results that looked at ATP production, bioenergetics and mitochondrial biogenesis.

Mitochondrial dysfunction due to matrix damage

Improving upon Neuroinflammation, Microglia and neurodegeneration ...

In the initial searches of both PubMed & Medline, using Neuroinflammation, Microglia and neurodegeneration as key words produced a large number of results, often too many to be sifted through in Covedence to choose the eventual systematic review articles to investigate more fully.

Two planned changes:

1. Mitochondria are at the heart of all neurodegenerative damage, so adding in either mitochondria or mitochondrial dysfunction or impairment to capture papers investigating the links between malfunctioning mitochondria and neurodegeneration
2. Adding in ATP as the resulting loss of cellular function and/or death is due to insufficient ATP being available. lack of ATP can be tracked to either mitochondrial impairment or insufficient ATP even though the mitochondria are fully functional, due to major trauma in the cell elsewhere causing the majority of ATP to be used to remedy this trauma leaving minimal ATP for other cellular use.

Preliminary testing of these search strings is showing large numbers of results when keywords is selected because this function tests for virtually all fields ie title, abstract headers. The next test to trim down the results and make the results more relevant is to potentially do a preliminary run using a key word and mapping this to the Mesh heading to select only those categories relevant to my research. 

Running this Mesh test resulted in roughly 250% more hits moving up from 632,900 to over 1,656,967 rather than less even though the search was restricted to those key categories of interest to my research.

The next test was to explode the Mesh headers chosen o see if we can make the target search more specific to drop the numbers further. 

Unfortunately, this further narrowing of the selection virtually doubled the selection from 1,656,967 items to over 2,435,049 items.

Microglial over activation and mitochondrial dysfunction

Searching on neurodegeneration, inflammation, blood based analysis for reserach on over-activation of microglia and mitochondrial dysfunction found no systematic reviews or simple litereature reviews.

"been there done that ..."

The initial idea for chapter one of my PhD was to do a Systematic Search on a topic that introduces the links between neuroinflammation and neurodegeneration. The immune response was a focus turning up across many of the articles read, with cytokines being investigated by many researchers, so this seemed a good place to start the summary.

Unfortunately there were already numerous review articles on the involvement of cytokines with inflammation and neurodegeneration, ruling this topic out as a possible systematic review.
Next I decided to investigate what triggered the immune system, and settles on macrophages, as they had both a signalling pathway role and performed phagocytosis on endotoxins, but again this topic had been done. So again I stepped back earlier to investigate the immune response and looked at the role of microglial, specifically the their role when there was an over-activation of the microglial. Over activation seemed to the showing up as a detrimental impact on dopaminergic neuronal cells causing a higher than normal level of apoptosis. Unfortunately this topic had also been summarised.

In each of the above topics, there was only one systematic review with all the other topics having had literature reviews done on them. The problem with these reviews was that there were not all that many with the majority being a number of years old and some quite poorly written. It was almost as if these researchers were not interested in their own original research, but wanted to get their publication count up and doing a review of someone else's work was just "low hanging fruit'. Thus the number of reviews in these areas was becoming a real stumbling block to getting started on my PhD because I could not find a unique area to summarise, that also set the scene for the types of experiments that would support my research into inflammation and neurodegeneration.

The next area I looked at was the impact on cellular energy requirements when neuroinflammation and the immune response over activated microglia damaging the mitochondria and causing apoptosis due to the cells not being able to sustain their energy requirements. Searching on this topic found no systematic reviews or literature reviews, which was a great start but a problem in that there may be very few studies to investigate. This means there is definitely a gap in the research but this same gap may make it hard to create a systematic review for publication.

However I have updated my PROSPERO application to reflect my findings with the new title being :

"The role of inflammation and microglial over activation in mitochondrial dysfunction and neurodegenerative progression: A Systematic Review"