EDITORIAL
published: 09 June 2022
doi: 10.3389/ ped.2022.933917
F on ie s in Pedia ics | www. on ie sin.o g 1June 2022 | Volume 10 | A icle 933917
Edi ed and e iewed by:
A jan Te Pas,
Leiden Uni e si y, Ne he lands
*Co espondence:
Daniel Alonso-Alconada
[email p o ec ed]
Special y sec ion:
This a icle was submi ed o
Neona ology,
a sec ion o he jou nal
F on ie s in Pedia ics
Recei ed: 01 May 2022
Accep ed: 25 May 2022
Published: 09 June 2022
Ci a ion:
Ca loni S, Ál a ez FJ and
Alonso-Alconada D (2022) Edi o ial:
Neona al B ain Inju y and he Sea ch
o New The apies.
F on . Pedia . 10:933917.
doi: 10.3389/ ped.2022.933917
Edi o ial: Neona al B ain Inju y and
he Sea ch o New The apies
Sil ia Ca loni1, F ancisco J. Ál a ez2and Daniel Alonso-Alconada3*
1Depa men o Biomolecula Sciences, Uni e si y o U bino Ca lo Bo, U bino, I aly, 2Bioc uces Bizkaia Heal h Resea ch
Ins i u e, C uces Uni e si y Hospi al, Ba akaldo, Spain, 3Depa men o Cell Biology and His ology, School o Medicine and
Nu sing, Uni e si y o he Basque Coun y (UPV/EHU), Leioa, Spain
Keywo ds: hypoxia-ischemia (HI), newbo n, neona al encephalopa hy (NE), b ain inju y, he apies, neu op o ec ion
Edi o ial on he Resea ch Topic
Neona al B ain Inju y and he Sea ch o New The apies
Hypoxia-ischemia is la gely ecognized as a majo cause o b ain inju y in he pe ina al pe iod
ha can lead o neona al encephalopa hy (1,2). When his occu s, i equen ly leads o neona al
mo ali y o o se e e long- e m neu ological de ici s in newbo ns wi h de as a ing consequences
bo h o he baby and i s amily, con ibu ing o o e 50 million disabili y-adjus ed li e yea s
wo ldwide each yea (3). The e o e, he s udy o he complex ela ionship among he di e en
mechanisms/ ac o s in ol ed in he inju y o he de eloping b ain and he inding o new
pha macological app oaches a e a high p io i y in pe ina al ca e. Acco dingly, he cha ac e iza ion
o pe iphe al ma ke s would help o p edic he de elopmen o pu a i e damage, and hei
modula ion a e pha macological ea men s may an icipa e i s e icacy as a po en ial he apeu ic
in e en ion o ansla ion o he clinical p ac ice.
The Resea ch Topic “Neona al B ain Inju y and he Sea ch o New The apies” includes no el
and o iginal con ibu ions in he s udy o neona al encephalopa hy wi h he aim o gi e a
comp ehensi e and g oundb eaking o e iew o he pa hophysiology and ea men o his disease.
O iginal epo s ha explo e and cla i y he p ognos ic alue o bioma ke s and speci ic diagnos ic
in e en ions a e included. This collec ion also highligh s he mos ecen e idences o new a ge s
o he apeu ic in e en ion. In his Resea ch Topic issue o F on ie s, we b ing oge he a special
collec ion o 15 a icles con ibu ing sound e idence o he key concep s ou lined.
Some pape s analyzed ele an peculia i ies o p e e m in an s as a sensible popula ion o
pa ien s a isk o b ain inju y. Ma e al. s udied he dynamic unc ional connec i i y in bo h
e m and la e p e e m in an s and obse ed ha he la e p e e ed o s ay in a s a e wi h gene al
weak connec i i y be ween ne wo ks; au ho s also ound ha his p e e ence declined as ma u i y
inc eased. Shaw e al. highligh ed ha he poo long- e m neu ode elopmen al and beha io al
ou comes obse ed in p e e m bi hs could be associa ed o an impai ed oligodend ocy e
de elopmen ; au ho s concluded ha p omo ing GABAe gic ac ion migh imp o e ou comes. In
an exhaus i e e iew, Shandley e al. ocused on he key ole o nu i ion o b ain de elopmen
in neona al li e, p o iding a wide- ange synopsis ega ding he ole o nu i i e and non-nu i i e
eeding in he neona e ou comes, he unde lying mechanisms in ol ed in neu ophysiology, and
he ela ionship o abno mal ac i i y wi h b ain inju y in p e e m and e m in an s. Te in e al.
e alua ed how p o ein in ake can a ec he ea ly ce eb al g ow h in e y low bi h weigh newbo ns,
showing ha se e al ce eb al s uc u es’ measu emen s we e a ec ed by high p o ein in ake when
adminis e ed by pa en al nu i ion, encou aging he adminis a ion mainly by en e al nu i ion.
Th ee o iginal s udies ocused on he impo an opic o he iden i ica ion o p ognos ic
ac o s ha could co ela e wi h he ongoing b ain damage. Zheng e al. showed ha pe usion
magne ic esonance imaging could ha e an impo an ole in he iden i ica ion o hypoxic-ischemic
Ca loni e al. Edi o ial: Neona al B ain Inju y and The apies
encephalopa hy, ega dless o indings on con en ional magne ic
esonance imaging, and in he p edic ion o language and
mo o ou comes. Zhu e al., in addi ion, e ealed ha mul i-
slice adiomic analysis based on appa en di usion coe icien s
me ics could p o ide mo e quan i a i e in o ma ion on
b ain de elopmen in neona es wi h congeni al hea diseases,
sugges ing ha hese measu emen s may be mo e clinically
help ul o iden i y a ypical b ain de elopmen in pa ien s. In
an o iginal s udy, Swee man e al. in es iga ed he connec ion
be ween high cy okines le els obse ed a e inna e immune
cell ac i a ion, b ain inju y and he ou come in in an s wi h
neona al encephalopa hy. Au ho s ound ha mode a e o se e e
encephalopa hy and mo ali y we e associa ed wi h ele a ed
in e leukin-8 and g anulocy e-mac ophage-colony-s imula ing-
ac o , poin ing ou ha hese cy okines may p edic ea ly
ou comes in neona al b ain inju y.
Se e al pape s p o ided new e idence o neu op o ec i e
s a egies. Fe nández e al. ound ha me hylene blue, a
guanylyl cyclase inhibi o wi h ee- adical sca enge p ope ies,
educed he e inal damage induced by pe ina al asphyxia in
he neona al a . Au ho s concluded ha me hylene blue could
egula e key playe s o in lamma ion, ma ix emodeling, gliosis
and angiogenesis in he eye, whose ea men may p e en
he dele e ious isual consequences o pe ina al asphyxia.
Yu e al. demons a ed ha he in anasal adminis a ion o
exogenous in e leukin-4 imp o ed myelina ion and a enua ed
he unc ional de ici s in a hypoxia-induced pe i en icula
leukomalacia model. Kolla e h e al. demons a ed ha
he acu e injec ion o docosahexaenoic acid iglyce ide
emulsion p o ided a e y simila p o ec ion as hypo he mia
in a neona al mouse model o hypoxic-ischemic b ain
inju y, indica ing an ad an ageous ea men in p o iding
a easible and e ec i e s a egy in pa ien s a e hypoxia-
ischemia inju y. Pu ohi e al. demons a ed ha he use
o human co d blood de i ed om un es ic ed soma ic
s em cells es o ed aquapo in channel exp ession, educed
in lamma ion and inhibi ed he de elopmen o hyd ocephalus
a e expe imen ally induced pe ina al in a en icula
hemo hage in abbi . Kasala e al. analyzed he e ec s o
he simul aneous use o mo phine and ca eine on b ain
de elopmen . Au ho s e ealed ha he concu en use o
mo phine, adminis e ed o p ema u e neona es o pain
con ol, and ca eine, used o apnea ea men , induced
apop osis and mi ochond ial dys unc ion in he de eloping
b ain compa ed o he indi idual use o he compounds.
Chan e al. discussed in an app op ia e e iew he links
be ween he espi a o y suppo o he p e e m neona e
and he b ain inju y pa e ns. Au ho s poin ed ha he use
o animal models a e essen ial esou ces o s udying he
pa hophysiology o en ila ion-induced b ain inju y, wi h
impo an ansla ional implica ions ha can be help ul o
ou line he way o ca e p e e m neona es, wi h he aim o
imp o e hei neu ode elopmen al ou comes.
As o oday, ad ances owa d new neu op o ec i e
in e en ions in hypoxic-ischemic encephalopa hy ha e been
limi ed by incomple e unde s anding o seconda y p ocesses.
Alonso-Alconada e al. desc ibed ha he sub en icula
zone could be a ec ed by neona al asphyxia. In hei wo k,
hypoxic-ischemic pigle s showed a dec ease in cellula i y
oge he wi h a educ ion in bo h cell p oli e a ion and
neu ogenesis in his neu ogenic niche, sugges ing ha asphyxia
could comp omise he eplacemen o he los neu ons
and he achie emen o global epai . In a comp ehensi e
e iew a icle, Kleuskens e al. p o ided an o e iew on
he pa hophysiology o ce eb al hype pe usion, commonly
obse ed du ing he i s 1–5 days in asphyc ic neona es.
Au ho s highligh ed he gaps in cu en unde s anding in
e m animals and neona es, analyzing da a om bo h he
hemodynamic changes and he endogenous pa hways in ol ed.
They concluded ha hese indings should be simul aneously
conside ed oge he wi h he b ain imagining echniques,
becoming a aluable esou ce in assessing he impac in
neu ode elopmen al ou come.
In summa y, his Resea ch Topic p o ides o iginal
a icles and e iews ha , oge he collec ed, may add
new in o ma ion on he epidemiology, pa hophysiology,
diagnosis and managemen o b ain inju y in he neona e,
also iden i ying ele an ea men s o es ing in u u e
clinical ials.
AUTHOR CONTRIBUTIONS
SC w o e he d a . FÁ and DA-A c i ically e iewed he
manusc ip . All au ho s con ibu ed o he a icle and app o ed
he submi ed e sion.
FUNDING
DA-A was suppo ed by EITB Ma a oia-BIOEF
(BIO18/IC/003) and he Spanish Minis y o Science and
Inno a ion (MINECOR20/P66/AEI/10.13039/501100011033).
ACKNOWLEDGMENTS
We would like o hank F on ie s o he oppo uni y o de elop
his opic and o he con ibu o s o hei ime and e o on his
p ojec . We specially hank all he e iewe s who p o ided use ul
sugges ions o imp o e he manusc ip s.
REFERENCES
1. Gunn AJ, Tho esen M. Neona al encephalopa hy and
hypoxic-ischemic encephalopa hy. Handb Clin Neu ol.
(2019) 162:217–37. doi: 10.1016/B978-0-444-64029-1.0
0010-2
2. Volpe JJ. Neona al encephalopa hy: an inadequa e e m o hypoxic-
ischemic encephalopa hy. Ann Neu ol. (2012) 72:156–66. doi: 10.1002/ana.2
3647
3. Lee AC, Kozuki N, Blencowe H, Vos T, Bahalim A, Da ms ad GL,
e al. In apa um- ela ed neona al encephalopa hy incidence and
impai men a egional and global le els o 2010 wi h ends om
F on ie s in Pedia ics | www. on ie sin.o g 2June 2022 | Volume 10 | A icle 933917
Ca loni e al. Edi o ial: Neona al B ain Inju y and The apies
1990. Pedia Res. (2013) 74(Suppl 1):50–72. doi: 10.1038/p .201
3.206
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