PMID- 29854942
OWN - NLM
STAT- MEDLINE
DCOM- 20190129
LR  - 20190129
IS  - 2373-2822 (Electronic)
IS  - 2373-2822 (Linking)
VI  - 5
IP  - 3
DP  - 2018 May-Jun
TI  - Blood-Brain Barrier Leakage during Early Epileptogenesis Is Associated with Rapid 
      Remodeling of the Neurovascular Unit.
LID - 10.1523/ENEURO.0123-18.2018 [doi]
LID - ENEURO.0123-18.2018
AB  - Increased permeability of the blood-brain barrier (BBB) following cerebral injury 
      results in regional extravasation of plasma proteins and can critically 
      contribute to the pathogenesis of epilepsy. Here, we comprehensively explore the 
      spatiotemporal evolution of a main extravasation component, albumin, and 
      illuminate associated responses of the neurovascular unit (NVU) contributing to 
      early epileptogenic neuropathology. We applied translational in vivo MR imaging 
      and complementary immunohistochemical analyses in the widely used rat pilocarpine 
      post-status epilepticus (SE) model. The observed rapid BBB leakage affected major 
      epileptogenesis-associated brain regions, peaked between 1 and 2 d post-SE, and 
      rapidly declined thereafter, accompanied by cerebral edema generally following 
      the same time course. At peak of BBB leakage, serum albumin colocalized with NVU 
      constituents, such as vascular components, neurons, and brain immune cells. 
      Surprisingly, astroglial markers did not colocalize with albumin, and aquaporin-4 
      (AQP4) was clearly reduced in areas of leaky BBB, indicating a severe disturbance 
      of astrocyte-mediated endothelial-neuronal coupling. In addition, a distinct 
      adaptive reorganization process of the NVU vasculature apparently takes place at 
      sites of albumin presence, substantiated by reduced immunoreactivity of 
      endothelial and changes in vascular basement membrane markers. Taken together, 
      degenerative events at the level of the NVU, affecting vessels, astrocytes, and 
      neurons, seem to outweigh reconstructive processes. Considering the rapidly 
      occurring BBB leakage and subsequent impairment of the NVU, our data support the 
      necessity of a prompt BBB-restoring treatment as one component of rational 
      therapeutic intervention to prevent epileptogenesis and the development of other 
      detrimental sequelae of SE.
FAU - Bankstahl, Marion
AU  - Bankstahl M
AUID- ORCID: 0000-0002-5775-188X
AD  - Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary 
      Medicine Hannover and Center for Systems Neuroscience, Bunteweg 17, Hannover, 
      30559, Germany.
FAU - Breuer, Heike
AU  - Breuer H
AD  - Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary 
      Medicine Hannover and Center for Systems Neuroscience, Bunteweg 17, Hannover, 
      30559, Germany.
AD  - Department of Nuclear Medicine, Hannover Medical School, Hannover, 30625, 
      Germany.
FAU - Leiter, Ina
AU  - Leiter I
AD  - Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary 
      Medicine Hannover and Center for Systems Neuroscience, Bunteweg 17, Hannover, 
      30559, Germany.
AD  - Department of Nuclear Medicine, Hannover Medical School, Hannover, 30625, 
      Germany.
FAU - Markel, Martin
AU  - Markel M
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, 04103, Germany.
FAU - Bascunana, Pablo
AU  - Bascunana P
AD  - Department of Nuclear Medicine, Hannover Medical School, Hannover, 30625, 
      Germany.
FAU - Michalski, Dominik
AU  - Michalski D
AD  - Department of Neurology, University of Leipzig, Liebigstr. 20, Leipzig, 04103, 
      Germany.
FAU - Bengel, Frank M
AU  - Bengel FM
AD  - Department of Nuclear Medicine, Hannover Medical School, Hannover, 30625, 
      Germany.
FAU - Loscher, Wolfgang
AU  - Loscher W
AD  - Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary 
      Medicine Hannover and Center for Systems Neuroscience, Bunteweg 17, Hannover, 
      30559, Germany.
FAU - Meier, Martin
AU  - Meier M
AD  - Preclinical Imaging Labs, Central Laboratory Animal Facility & Institute for 
      Laboratory Animal Science, Hannover Medical School, Hannover, 30625, Germany.
FAU - Bankstahl, Jens P
AU  - Bankstahl JP
AD  - Department of Nuclear Medicine, Hannover Medical School, Hannover, 30625, 
      Germany.
FAU - Hartig, Wolfgang
AU  - Hartig W
AD  - Paul Flechsig Institute for Brain Research, University of Leipzig, Liebigstr. 19, 
      Leipzig, 04103, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180530
PL  - United States
TA  - eNeuro
JT  - eNeuro
JID - 101647362
RN  - 0 (Albumins)
RN  - 0 (FITC-albumin)
RN  - 0 (Serum Albumin)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Albumins/metabolism
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Blood-Brain Barrier/*metabolism/*physiopathology
MH  - Brain/*metabolism/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Fluorescein-5-isothiocyanate/analogs & derivatives/metabolism
MH  - Neurons/metabolism
MH  - Pilocarpine
MH  - Rats, Sprague-Dawley
MH  - Serum Albumin/metabolism
MH  - Status Epilepticus/chemically induced/*metabolism/pathology
PMC - PMC5975718
OTO - NOTNLM
OT  - Blood-Brain Barrier
OT  - Epileptogenesis
OT  - MR Imaging
OT  - Neurovascular Unit
EDAT- 2018/06/02 06:00
MHDA- 2019/01/30 06:00
PMCR- 2018/05/30
CRDT- 2018/06/02 06:00
PHST- 2018/03/29 00:00 [received]
PHST- 2018/04/01 00:00 [accepted]
PHST- 2018/06/02 06:00 [entrez]
PHST- 2018/06/02 06:00 [pubmed]
PHST- 2019/01/30 06:00 [medline]
PHST- 2018/05/30 00:00 [pmc-release]
AID - eN-NWR-0123-18 [pii]
AID - 10.1523/ENEURO.0123-18.2018 [doi]
PST - epublish
SO  - eNeuro. 2018 May 30;5(3):ENEURO.0123-18.2018. doi: 10.1523/ENEURO.0123-18.2018. 
      eCollection 2018 May-Jun.