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Tanaka. Neuroimmunol Neuroinflammation 2020;7:73-91 I http://dx.doi.org/10.20517/2347-8659.2020.04 Page 87

attributed to ameliorated neuronal survival rather than the direct effects on macrophages and microglia.
Thus, an agent that can increase expression of anti-apoptotic factors in neurons would increase the number
of favorable microglia and macrophages.

Ginsenosides are natural products isolated from the plant ginseng. Among the ginsenosides, ginsenoside
[105]
[106]
Rb1 and its derivatives strongly ameliorate the outcome of stroke and TBI models, while increasing
Bcl-xl expression. Along with their direct effects on neurons, ginsenosides have been shown to inhibit the
proinflammatory activation of microglia. It remains to be determined whether they inhibit LPS-induced
proinflammatory activation of microglia and macrophages [107,108] .

CONCLUSION
Microglia and macrophages have profound effects on the pathophysiological processes of several brain
pathologies. They become activated in response to pathological changes of neurons that produce DAMPs
and express PS on their surface. Microglia and macrophages can have ameliorative and/or deleterious
effects on the CNS depending on the severity of the disease or injuries, time course, and BBB disruption.
Even within the same pathology, the cells exert both different effects in completely different ways, as
described in the cases of PD and the spinal cord of the peripheral nerve injury model. The development
of pharmacological interventions to regulate the response of microglia and macrophages has long been
anticipated. However much more research into their responses is required before that goal can be attained.

DECLARATIONS
Acknowledgments
The author would like to thank Enago (www.enago.jp) for the English language review.

Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

REFERENCES
1. Jian Z, Liu R, Zhu X, Smerin D, Zhong Y, et al. The involvement and therapy target of immune cells after ischemic stroke. Front
Immunol 2019;10:2167.