PMID- 25059512
OWN - NLM
STAT- MEDLINE
DCOM- 20150914
LR  - 20150117
IS  - 1440-1789 (Electronic)
IS  - 0919-6544 (Linking)
VI  - 35
IP  - 1
DP  - 2015 Feb
TI  - Excitatory amino acid transporter 2 downregulation correlates with thalamic 
      neuronal death following kainic acid-induced status epilepticus in rat.
PG  - 1-9
LID - 10.1111/neup.12141 [doi]
AB  - Recurrent seizures without interictal resumption (status epilepticus) have been 
      reported to induce neuronal death in the midline thalamic region that has 
      functional roles in memory and decision-making; however, the pathogenesis 
      underlying status epilepticus-induced thalamic neuronal death is yet to be 
      determined. We performed histological and immunohistochemical studies as well as 
      cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging 
      spectrometer on midline thalamic region in Sprague-Dawley rats (n = 75, male, 7 
      weeks after birth, body weight 250-300 g) treated with intraperitoneal injection 
      of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline 
      solution (n = 20). Histological study using paraffin-embedded specimens revealed 
      neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with 
      calcium deposition in the midline thalamic region of epileptic rats. The 
      distribution of neuronal death was associated with focal loss of immunoreactivity 
      for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for 
      glutamate and increase in number of Iba-1-positive microglial cells showing 
      swollen cytoplasm and long processes. Double immunofluorescence study 
      demonstrated co-expression of interleukin-1 beta (IL-1beta) and inducible nitric 
      oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity 
      in reactive astrocytes. These microglial alterations and astrocytic EAAT2 
      downregulation were also observed in tissue without obvious neuronal death in 
      kainic acid-treated rats. These results suggest the possible role of glutamate 
      excitotoxicity in neuronal death in the midline thalamic region following kainic 
      acid-induced status epilepticus due to astrocytic EAAT2 downregulation following 
      microglial activation showing upregulation of IL-1beta and iNOS.
CI  - (c) 2014 Japanese Society of Neuropathology.
FAU - Sakurai, Masashi
AU  - Sakurai M
AD  - Department of Veterinary Pathology, Tottori University, Tottori, Japan.
FAU - Kurokawa, Haruna
AU  - Kurokawa H
FAU - Shimada, Akinori
AU  - Shimada A
FAU - Nakamura, Kazuhiro
AU  - Nakamura K
FAU - Miyata, Hajime
AU  - Miyata H
FAU - Morita, Takehito
AU  - Morita T
LA  - eng
PT  - Journal Article
DEP - 20140724
PL  - Australia
TA  - Neuropathology
JT  - Neuropathology : official journal of the Japanese Society of Neuropathology
JID - 9606526
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - 0 (Slc1a2 protein, rat)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Cell Death
MH  - Down-Regulation
MH  - Excitatory Amino Acid Transporter 2/*metabolism
MH  - Kainic Acid
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Microglia/metabolism
MH  - Midline Thalamic Nuclei/blood supply/*metabolism/*pathology
MH  - Neurons/cytology/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Status Epilepticus/chemically induced/*metabolism/*pathology
OTO - NOTNLM
OT  - epilepsy
OT  - excitatory amino acid transporter 2
OT  - neuronal death
OT  - status epilepticus
OT  - thalamus
EDAT- 2014/07/26 06:00
MHDA- 2015/09/15 06:00
CRDT- 2014/07/26 06:00
PHST- 2014/04/21 00:00 [received]
PHST- 2014/05/15 00:00 [accepted]
PHST- 2014/07/26 06:00 [entrez]
PHST- 2014/07/26 06:00 [pubmed]
PHST- 2015/09/15 06:00 [medline]
AID - 10.1111/neup.12141 [doi]
PST - ppublish
SO  - Neuropathology. 2015 Feb;35(1):1-9. doi: 10.1111/neup.12141. Epub 2014 Jul 24.