April 4, 2023, by mbzva
Neuroinflammation: the doubled edged sword of the brain
By Ryan Duffy, 4th Year Neuroscience MSci
Inflammation is a biological process that is critical in the defence of an organism and enables repair and recovery from damage to tissues. Inflammation is very common, and it occurs in many different species including humans. Inflammation can occur when we damage part of our body either through impact, or through infection. Our immune system then recognises that there is damage to tissue or invasion of a bacteria and it causes blood and immune cells to rush to the site of injury, causing that painful, swollen, and red site of inflammation that we have all experienced. Once all the dead tissue/bacteria has been cleared up, the inflammation resolves and the immune cells disperse back into the blood, causing the swelling to go away (1). This process is normal, and it’s really helpful to prevent the damage from spreading to other parts of the body, as well as stop us from touching/using the damaged area so the immune cells can work their magic.
Like many biological processes you can have too much of a good thing, and the same is true for inflammation. In many neurological diseases, we see chronic inflammation that can lead to overactivation of the immune system. In these cases an overactive immune system can lead to autoimmune reactions, which means our body is actually attacking itself (2). To get around this issue, researchers have started to understand the components behind inflammation, and deepen our knowledge on the good, the bad, and the ugly of this double-edged sword.
Inflammation can also occur in the brain, in this case it is considered “neuroinflammation”, which molecularly is very similar to peripheral immune inflammation, however, in the brain neuroinflammation is mediated by specialised central nervous system (CNS) immune cells, known as microglia. As the name suggests, microglia are very small cells that survey our CNS, becoming activated when a threat is detected, such as tissue damage. In this context, the microglia release inflammatory mediators to induce neuroinflammation, which starts the process of tissue repair (3).
In many diseases, neuroinflammation can have a neuroprotective role and prevent further damage from occurring. The most common example of this is in stroke. During a brain bleed, microglia can become active to clear hematoma’s and dead tissue, which has a neuroprotective role, in a “cut your losses” type mechanism (4). However, also in stroke the same mechanism can be detrimental to the patient in cases of prolonged inflammation. If microglia sustain neuroinflammation after the damaged tissue has been removed, they can begin to remove healthy tissue, in a process called autoimmune damage, meaning the microglia have mistaken the healthy tissue for damaged tissue, leading to devastating changes to the brain, and therefore, leading to disability in many stroke patients (5).
Knowing this, we can start to see that neuroinflammation isn’t the problem in this disease, but it is the timing and level that determines if this immune interaction is protective or detrimental to brain tissue. So how can we treat a mechanism that is helping one minute and hindering the next? One-way researchers have tried to do this is through the use of stem cells, which have shown promising results for patients suffering from detrimental neuroinflammation post stroke. Stem cells have been effective due to their anti-inflammatory, anti-oxidative, and anti-apoptotic factors, meaning they guard against neuroinflammation and can prevent damage to healthy tissue (6). Stem cells have also been shown to have neurogenitive effects, meaning they also permit the growth of new tissue, improving the recovery and maintaining cognitive function in stroke patients. It is possible that in the future, stems cells could be used in conjunction with other medications to give patients suffering from neuroinflammatory disorders the best chance of recovery.
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- Terrando N, Pavlov VA. Editorial: Neuro-Immune Interactions in Inflammation and Autoimmunity. Front Immunol [Internet]. 2018;9. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2018.00772
- Muzio L, Viotti A, Martino G. Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy. Front Neurosci [Internet]. 2021;15. Available from: https://www.frontiersin.org/articles/10.3389/fnins.2021.742065
- Dabrowska S, Andrzejewska A, Lukomska B, Janowski M. Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles. J Neuroinflammation [Internet]. 2019;16(1):178. Available from: https://doi.org/10.1186/s12974-019-1571-8
- Lian L, Zhang Y, Liu L, Yang L, Cai Y, Zhang J, et al. Neuroinflammation in Ischemic Stroke: Focus on MicroRNA-mediated Polarization of Microglia. Front Mol Neurosci [Internet]. 2021;13. Available from: https://www.frontiersin.org/articles/10.3389/fnmol.2020.612439
- Tuazon JP, Castelli V, Borlongan C V. Drug-like delivery methods of stem cells as biologics for stroke. Expert Opin Drug Deliv. 2019 Aug;16(8):823–33.
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