Inter-alpha inhibitor proteins attenuate lipopolysaccharide-induced blood-brain barrier disruption in neonatal mice
Copyright © 2023 Elsevier Inc. All rights reserved..
There is a paucity of information regarding efficacious pharmacological neuroprotective strategies to attenuate or reduce brain injury in neonates. Lipopolysaccharide (LPS) disrupts blood-brain barrier (BBB) function in adult rodents and increases inflammation in adults and neonates. Human blood-derived Inter-alpha Inhibitor Proteins (IAIPs) are neuroprotective, improve neonatal survival after LPS, and attenuate LPS-induced disruption of the BBB in adult male mice. We hypothesized that LPS also disrupts the function of the BBB in neonatal mice and that IAIPs attenuate the LPS-induced BBB disruption in male and female neonatal mice. IAIPs were administered to neonatal mice after LPS and BBB permeability quantified with intravenous 14C-sucrose and 99mTc-albumin. Although repeated high doses (3 mg/kg) of LPS in neonates resulted in high mortality rates and a robust increase in BBB permeability, repeated lower doses (1 mg/kg) of LPS resulted in lower mortality rates and disruption of the BBB in both male and female neonates. IAIP treatment attenuated disruption of the BBB similarly to sucrose and albumin after exposure to low-dose LPS in neonatal mice. Exposure to low-dose LPS elevated IAIP concentrations in blood, but it did not appear to increase the systemic levels of Pre-alpha inhibitor (PaI), one of the family members of the IAIPs that contains heavy chain 3. We conclude that IAIPs attenuate LPS-related disruption of the BBB in both male and female neonatal mice.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:370 |
---|---|
Enthalten in: |
Experimental neurology - 370(2023) vom: 01. Dez., Seite 114563 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Logsdon, Aric F [VerfasserIn] |
---|
Links: |
---|
Themen: |
57-50-1 |
---|
Anmerkungen: |
Date Completed 10.11.2023 Date Revised 13.11.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.expneurol.2023.114563 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM363001042 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM363001042 | ||
003 | DE-627 | ||
005 | 20231226092423.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.expneurol.2023.114563 |2 doi | |
028 | 5 | 2 | |a pubmed24n1209.xml |
035 | |a (DE-627)NLM363001042 | ||
035 | |a (NLM)37806514 | ||
035 | |a (PII)S0014-4886(23)00248-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Logsdon, Aric F |e verfasserin |4 aut | |
245 | 1 | 0 | |a Inter-alpha inhibitor proteins attenuate lipopolysaccharide-induced blood-brain barrier disruption in neonatal mice |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 10.11.2023 | ||
500 | |a Date Revised 13.11.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 Elsevier Inc. All rights reserved. | ||
520 | |a There is a paucity of information regarding efficacious pharmacological neuroprotective strategies to attenuate or reduce brain injury in neonates. Lipopolysaccharide (LPS) disrupts blood-brain barrier (BBB) function in adult rodents and increases inflammation in adults and neonates. Human blood-derived Inter-alpha Inhibitor Proteins (IAIPs) are neuroprotective, improve neonatal survival after LPS, and attenuate LPS-induced disruption of the BBB in adult male mice. We hypothesized that LPS also disrupts the function of the BBB in neonatal mice and that IAIPs attenuate the LPS-induced BBB disruption in male and female neonatal mice. IAIPs were administered to neonatal mice after LPS and BBB permeability quantified with intravenous 14C-sucrose and 99mTc-albumin. Although repeated high doses (3 mg/kg) of LPS in neonates resulted in high mortality rates and a robust increase in BBB permeability, repeated lower doses (1 mg/kg) of LPS resulted in lower mortality rates and disruption of the BBB in both male and female neonates. IAIP treatment attenuated disruption of the BBB similarly to sucrose and albumin after exposure to low-dose LPS in neonatal mice. Exposure to low-dose LPS elevated IAIP concentrations in blood, but it did not appear to increase the systemic levels of Pre-alpha inhibitor (PaI), one of the family members of the IAIPs that contains heavy chain 3. We conclude that IAIPs attenuate LPS-related disruption of the BBB in both male and female neonatal mice | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Bikunin | |
650 | 4 | |a Blood-brain barrier | |
650 | 4 | |a Heavy chains | |
650 | 4 | |a Lipopolysaccharide | |
650 | 4 | |a Neonatal | |
650 | 4 | |a Urinary trypsin inhibitors | |
650 | 7 | |a Lipopolysaccharides |2 NLM | |
650 | 7 | |a Albumins |2 NLM | |
650 | 7 | |a Sucrose |2 NLM | |
650 | 7 | |a 57-50-1 |2 NLM | |
700 | 1 | |a Erickson, Michelle A |e verfasserin |4 aut | |
700 | 1 | |a Herbert, Melanie J |e verfasserin |4 aut | |
700 | 1 | |a Noonan, Cassidy |e verfasserin |4 aut | |
700 | 1 | |a Foresi, Brian D |e verfasserin |4 aut | |
700 | 1 | |a Qiu, Joseph |e verfasserin |4 aut | |
700 | 1 | |a Lim, Yow-Pin |e verfasserin |4 aut | |
700 | 1 | |a Banks, William A |e verfasserin |4 aut | |
700 | 1 | |a Stonestreet, Barbara S |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Experimental neurology |d 1959 |g 370(2023) vom: 01. Dez., Seite 114563 |w (DE-627)NLM000016624 |x 1090-2430 |7 nnns |
773 | 1 | 8 | |g volume:370 |g year:2023 |g day:01 |g month:12 |g pages:114563 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.expneurol.2023.114563 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 370 |j 2023 |b 01 |c 12 |h 114563 |