PMID- 36508265
OWN - NLM
STAT- MEDLINE
DCOM- 20230306
LR  - 20240322
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Print)
IS  - 0897-7151 (Linking)
VI  - 40
IP  - 5-6
DP  - 2023 Mar
TI  - Partial Depletion of Microglia Attenuates Long-Term Potentiation Deficits 
      following Repeated Blast Traumatic Brain Injury in Organotypic Hippocampal Slice 
      Cultures.
PG  - 547-560
LID - 10.1089/neu.2022.0284 [doi]
AB  - Blast-induced traumatic brain injury (bTBI) has been a health concern in both 
      military and civilian populations due to recent military and geopolitical 
      conflicts. Military service members are frequently exposed to repeated bTBI 
      throughout their training and deployment. Our group has previously reported 
      compounding functional deficits as a result of increased number of blast 
      exposures. In this study, we further characterized the decrease in long-term 
      potentiation (LTP) by varying the blast injury severity and the inter-blast 
      interval between two blast exposures. LTP deficits were attenuated with 
      increasing inter-blast intervals. We also investigated changes in microglial 
      activation; expression of CD68 was increased and expression of CD206 was 
      decreased after multiple blast exposures. Expression of macrophage inflammatory 
      protein (MIP)-1alpha, interleukin (IL)-1beta, monocyte chemoattractant protein (MCP)-1, 
      interferon gamma-inducible protein (IP)-10, and regulated on activation, normal T 
      cell expressed and secreted (RANTES) increased, while expression of IL-10 
      decreased in the acute period after both single and repeated bTBI. By partially 
      depleting microglia prior to injury, LTP deficits after injury were significantly 
      reduced. Treatment with the novel drug, MW-189, prevented LTP deficits when 
      administered immediately following a repeated bTBI and even when administered 
      only for an acute period (24 h) between two blast injuries. These findings could 
      inform the development of therapeutic strategies to treat the neurological 
      deficits of repeated bTBI suggesting that microglia play a major role in 
      functional neuronal deficits and may be a viable therapeutic target to lessen the 
      neurophysiological deficits after bTBI.
FAU - Varghese, Nevin
AU  - Varghese N
AD  - Department of Biomedical Engineering, Columbia University, New York, New York, 
      USA.
FAU - Morrison, Barclay 3rd
AU  - Morrison B 3rd
AD  - Department of Biomedical Engineering, Columbia University, New York, New York, 
      USA.
LA  - eng
GR  - UL1 TR001873/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20221012
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
SB  - IM
MH  - Humans
MH  - Long-Term Potentiation/physiology
MH  - Microglia
MH  - *Brain Injuries, Traumatic
MH  - Explosions
MH  - Hippocampus
MH  - *Blast Injuries/complications
PMC - PMC10081725
OTO - NOTNLM
OT  - electrophysiology
OT  - hippocampus
OT  - long-term potentiation
OT  - microglial depletion
OT  - repeated blast traumatic brain injury
COIS- No competing financial interests exist.
EDAT- 2022/12/13 06:00
MHDA- 2023/03/07 06:00
PMCR- 2024/03/01
CRDT- 2022/12/12 12:13
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2023/03/07 06:00 [medline]
PHST- 2022/12/12 12:13 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - 10.1089/neu.2022.0284 [pii]
AID - 10.1089/neu.2022.0284 [doi]
PST - ppublish
SO  - J Neurotrauma. 2023 Mar;40(5-6):547-560. doi: 10.1089/neu.2022.0284. Epub 2022 
      Oct 12.