PMID- 12486156
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20201226
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 22
IP  - 24
DP  - 2002 Dec 15
TI  - Pertussis toxin-induced reversible encephalopathy dependent on monocyte 
      chemoattractant protein-1 overexpression in mice.
PG  - 10633-42
AB  - In this report we describe pertussis toxin-induced reversible encephalopathy 
      dependent on monocyte chemoattractant protein-1 (MCP-1) overexpression (PREMO), a 
      novel animal model that exhibits features of human encephalopathic complications 
      of inflammatory disorders such as viral meningoencephalitis and Lyme 
      neuroborreliosis as well as the mild toxic encephalopathy that commonly precedes 
      relapses of multiple sclerosis (MS). Overexpression of the mouse MCP-1 gene 
      product (classically termed JE) in astrocytes, the major physiological CNS 
      cellular source of MCP-1, failed to induce neurological impairment. Unexpectedly, 
      transgenic (tg) mice overexpressing MCP-1 at a high level (MCP-1(hi)) manifested 
      transient, severe encephalopathy with high mortality after injections of 
      pertussis toxin (PTx) plus complete Freund's adjuvant (CFA). Surviving mice 
      showed markedly improved function and did not relapse during a prolonged period 
      of observation. Tg mice that expressed lower levels of MCP-1 were affected 
      minimally after CFA/PTx injections, and tg expression of other chemokines failed 
      to elicit this disorder. The disorder was significantly milder in mice lacking 
      T-cells, which therefore play a deleterious role in this encephalopathic process. 
      Disruption of CC chemokine receptor 2 (CCR2) abolished both CNS inflammation and 
      encephalopathy, identifying CCR2 as a relevant receptor for this disorder. 
      Proinflammatory and type 1 cytokines including TNF-alpha, IL-1beta, IFN-gamma, 
      IL-2, RANTES, and IP-10 were elevated in CNS tissues from mice with PREMO. These 
      studies characterize a novel model of reversible inflammatory encephalopathy that 
      is dependent on both genetic and environmental factors.
FAU - Huang, DeRen
AU  - Huang D
AD  - Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic 
      Foundation, Cleveland, Ohio 44195, USA.
FAU - Tani, Marie
AU  - Tani M
FAU - Wang, Jintang
AU  - Wang J
FAU - Han, Yulong
AU  - Han Y
FAU - He, Toby T
AU  - He TT
FAU - Weaver, Jennifer
AU  - Weaver J
FAU - Charo, Israel F
AU  - Charo IF
FAU - Tuohy, Vincent K
AU  - Tuohy VK
FAU - Rollins, Barrett J
AU  - Rollins BJ
FAU - Ransohoff, Richard M
AU  - Ransohoff RM
LA  - eng
GR  - R01 NS032151/NS/NINDS NIH HHS/United States
GR  - 2R01 NS32151-09/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (CCR2 protein, human)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Cell Movement
MH  - Central Nervous System/immunology/pathology
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Chemokines/biosynthesis/genetics
MH  - Cytokines/biosynthesis/genetics
MH  - Encephalitis/chemically induced/diagnosis/*immunology
MH  - Glial Fibrillary Acidic Protein/genetics
MH  - Humans
MH  - Leukocytes/immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Pertussis Toxin
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics/physiology
MH  - Survival Analysis
MH  - T-Lymphocytes/immunology
PMC - PMC6758405
EDAT- 2002/12/18 04:00
MHDA- 2003/01/24 04:00
PMCR- 2003/06/15
CRDT- 2002/12/18 04:00
PHST- 2002/12/18 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/12/18 04:00 [entrez]
PHST- 2003/06/15 00:00 [pmc-release]
AID - 22/24/10633 [pii]
AID - 7099 [pii]
AID - 10.1523/JNEUROSCI.22-24-10633.2002 [doi]
PST - ppublish
SO  - J Neurosci. 2002 Dec 15;22(24):10633-42. doi: 10.1523/JNEUROSCI.22-24-10633.2002.