PMID- 33991400
OWN - NLM
STAT- MEDLINE
DCOM- 20210910
LR  - 20220902
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Print)
IS  - 1748-1708 (Linking)
VI  - 233
IP  - 1
DP  - 2021 Sep
TI  - Microglia-leucocyte axis in cerebral ischaemia and inflammation in the developing 
      brain.
PG  - e13674
LID - 10.1111/apha.13674 [doi]
AB  - Development of the Central Nervous System (CNS) is reliant on the proper function 
      of numerous intricately orchestrated mechanisms that mature independently, 
      including constant communication between the CNS and the peripheral immune 
      system. This review summarizes experimental knowledge of how cerebral ischaemia 
      in infants and children alters physiological communication between leucocytes, 
      brain immune cells, microglia and the neurovascular unit (NVU)-the 
      "microglia-leucocyte axis"-and contributes to acute and long-term brain injury. 
      We outline physiological development of CNS barriers in relation to microglial 
      and leucocyte maturation and the plethora of mechanisms by which microglia and 
      peripheral leucocytes communicate during postnatal period, including 
      receptor-mediated and intracellular inflammatory signalling, lipids, soluble 
      factors and extracellular vesicles. We focus on the "microglia-leucocyte axis" in 
      rodent models of most common ischaemic brain diseases in the at-term infants, 
      hypoxic-ischaemic encephalopathy (HIE) and focal arterial stroke and discuss 
      commonalities and distinctions of immune-neurovascular mechanisms in neonatal and 
      childhood stroke compared to stroke in adults. Given that hypoxic and ischaemic 
      brain damage involve Toll-like receptor (TLR) activation, we discuss the 
      modulatory role of viral and bacterial TLR2/3/4-mediated infection in HIE, 
      perinatal and childhood stroke. Furthermore, we provide perspective of the 
      dynamics and contribution of the axis in cerebral ischaemia depending on the CNS 
      maturational stage at the time of insult, and modulation independently and in 
      consort by individual axis components and in a sex dependent ways. Improved 
      understanding on how to modify crosstalk between microglia and leucocytes will 
      aid in developing age-appropriate therapies for infants and children who suffered 
      cerebral ischaemia.
CI  - (c) 2021 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
FAU - Rayasam, Aditya
AU  - Rayasam A
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Fukuzaki, Yumi
AU  - Fukuzaki Y
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA, USA.
FAU - Vexler, Zinaida S
AU  - Vexler ZS
AUID- ORCID: 0000-0002-6491-1562
AD  - Department of Neurology, University of California San Francisco, San Francisco, 
      CA, USA.
LA  - eng
GR  - R01NS103483/RG/CSR NIH HHS/United States
GR  - RO1NS76726/RG/CSR NIH HHS/United States
GR  - R21NS098514/RG/CSR NIH HHS/United States
GR  - R01 NS044025/NS/NINDS NIH HHS/United States
GR  - RO1NS44025/RG/CSR NIH HHS/United States
GR  - R21 NS098514/NS/NINDS NIH HHS/United States
GR  - R01 HL139685/HL/NHLBI NIH HHS/United States
GR  - R01 NS103483/NS/NINDS NIH HHS/United States
GR  - R01 NS076726/NS/NINDS NIH HHS/United States
GR  - R01HL139685/RG/CSR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210530
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
SB  - IM
MH  - Brain
MH  - Child
MH  - Female
MH  - Humans
MH  - *Hypoxia-Ischemia, Brain
MH  - Inflammation
MH  - Microglia
MH  - Pregnancy
MH  - *Stroke
PMC - PMC9093042
MID - NIHMS1730882
OTO - NOTNLM
OT  - T cells
OT  - immune cells
OT  - monocytes
OT  - neonatal stroke
OT  - neuroinflammation
OT  - neutrophils
COIS- Conflict of Interest: None
EDAT- 2021/05/16 06:00
MHDA- 2021/09/11 06:00
PMCR- 2022/09/01
CRDT- 2021/05/15 12:13
PHST- 2021/05/06 00:00 [revised]
PHST- 2020/09/30 00:00 [received]
PHST- 2021/05/08 00:00 [accepted]
PHST- 2021/05/16 06:00 [pubmed]
PHST- 2021/09/11 06:00 [medline]
PHST- 2021/05/15 12:13 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - 10.1111/apha.13674 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2021 Sep;233(1):e13674. doi: 10.1111/apha.13674. Epub 2021 
      May 30.