VIRUSES INFLAME NERVE CELLS. HERE’S HOW TO FIGHT NEUROINFLAMMATION

In the Central Nervous System (CNS), the immune response plays an important role in virus protection. Our immune system, however, is not able to intervene directly on our brain, so in addition to the protection provided by the blood-brain barrier, only indirectly induced immune responses can protect our Nervous System.

Essential to protect the CNS from viral infections is the blood-brain barrier (BBB). BBB limits the entry of invading toxins and pathogens, including viruses, into the CNS. Viruses may be able to interrupt BBB and invade nerve cells. Infection causes rapid induction of chemokines from astrocytes and microglia.

Astrocytes are nerve cells that perform a variety of neuroprotective functions. They provide metabolic support for neurons and synaptic function, regulate the extracellular balance of ions and neurotransmitters and maintain the integrity of BBB. In addition, these glial cells play a role in the control of traffic and activation of immune cells. Astrocytes can detect signs of damage and respond by secreting cytokines and chemokines and activating immune defenses.

Figure by Nakagawa Y and Chiba K_Pharmaceuticals 2014, 7(12), 1028-1048; Review

Microglia protects the CNS from viral infection through various mechanisms, including the production of antiviral cytokines, phagocytosis of virus-infected and dying neurons and induction of neuronal repair and homeostasis of the brain. In addition to limiting viral replication, microglia orchestrates the peripheral immune response to invading pathogens. Microglia can assume several phenotypes: an M1 phenotype that expresses pro-inflammatory cytokines and is capable of killing cells foreign to our body, and an M2 phenotype for phagocytosis of cell debris, resolution of inflammation and tissue repair.

Once in the body, a virus triggers a series of immune responses that leads our cells to defend themselves by secreting a wide variety of molecules, such as cytokines, chemokines, T cells, B cells, monocytes and macrophages, which learn to attack and destroy the virus or cells it has infected. However, this defence mechanism, if prolonged, can have negative consequences for the CNS.

Pro-inflammatory cytokines can be harmful in the long term to neuronal function and regeneration. Recruitment of monocytes into the central nervous system to reduce the viral load may be hijacked by viral machinery and lead to an increase in the CNS viral load in specific cases. In addition, prolonged microglial activation after infection can cause neuronal damage mediated by astrocytes.

This inflammatory state, called neuroinflammation, consists of a complex cascade of biological events through which, starting from the activation of the microglia, an inflammatory state is produced that persists beyond normal physiological duration, causing a progressive pathological condition and increasing the risk of neurological pathologies.

Our immune system is not able to intervene directly in the brain, so only other types of immune responses, such as NIR-stimulated effects, can reduce inflammation and keep our brain healthy.

Evidence suggests that NIR photobiomodulation therapy can be used to reduce inflammation in the brain.

There is a lot of scientific evidence to support that NIR can activate mitochondrial metabolism towards oxidative phosphorylation at the microglia level and that it can change the microglial phenotype from M1 to M2. The consequence of this change would be that instead of the M1 microglia, which generates inflammatory cytokines, the NIR-induced M2 microglia would be able to cleanse the system, exert anti-inflammatory and antioxidant effects and promote tissue regeneration.

In addition, NIR has the ability to modulate the levels of cytokines, proteins that act as important signal molecules for the nervous system. NIR has demonstrated the ability to modulate the levels of both pro and anti-inflammatory cytokines by reducing inflammation, through its ability to modulate levels of tumor necrosis factor (TNF) and other pro-inflammatory cytokines.

Therefore, NIR treatment can help prevent and alleviate post-viral neuroinflammation, a condition that if prolonged causes brain damage that can cause neurological disorders.

In May, Cerebro® is planning a Webinar to deepen the topic.

By Rosjana Pica

Biologist

In collaboration with Cerebro® Staff

Cerebro ® , an Innovativation and High-Tech Neuroscience Start-Up, which helps patients in medical practices and associated clinics through different methods and approaches to improve the perception and quality of life of each individual.

Bibliography

Kalia M, Jameel S. “Virus entry paradigms”. Amino Acids. 2011 Nov;41(5):1147-57. doi: 10.1007/s00726-009-0363-3. Epub 2009 Oct 15.

Frost JL, Schafer DP. “Microglia: Architects of the Developing Nervous System”. Trends in Cell Biology, vol. 26, no. 8, pp. 587–597, 2016.

Klein RS, Garber C, Funk KE, Salimi H, Soung A, Kanmogne M, Manivasagam S, Agner S, Cain M. “Neuroinflammation During RNA Viral Infections”. Annu Rev Immunol. 2019 Apr 26;37:73-95.

Chen Z, Trapp BD. “Microglia and neuroprotection”. J Neurochem. 2016 Jan;136 Suppl 1:10-7. doi: 10.1111/jnc.13062. Epub 2015 Mar 10.

Singer AC, Martorell AJ, Douglas JM, Abdurrob F, Attokaren MK, Tipton J, Mathys H, Adaikkan C, Tsai LH.  “Noninvasive 40-Hz light flicker to recruit microglia and reduce amyloid beta load”. Nat Protoc. 2018 Aug;13(8):1850-1868.

Sharma SK, Kharkwal GB, Sajo M, Huang YY, De Taboada L, McCarthy T, Hamblin MR. “Dose response effects of 810 nm laser light on mouse primary cortical neurons”. Lasers Surg Med. 2011 Sep;43(8):851-9.

Condividi