RGD Reference Report - Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage. - Rat Genome Database

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Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage.

Authors: Louboutin, JP  Chekmasova, A  Marusich, E  Agrawal, L  Strayer, DS 
Citation: Louboutin JP, etal., FASEB J. 2010 Oct 12.
RGD ID: 4889880
Pubmed: PMID:20940264   (View Abstract at PubMed)
PMCID: PMC3023386   (View Article at PubMed Central)
DOI: DOI:10.1096/fj.10-161851   (Journal Full-text)

Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. We investigated the role of the chemokine receptor CCR5 in seizures. We used a rat model based on intraperitoneal kainic acid (KA) administration. Four months before KA injection, adult rats were given femoral intramarrow inoculations of SV (RNAiR5-RevM10.AU1), which carries an interfering RNA (RNAi) against CCR5, plus a marker epitope (AU1), or its monofunctional RNAi-carrying homologue, SV(RNAiR5). This treatment lowered expression of CCR5 in circulating cells. In control rats, seizures induced elevated expression of CCR5 ligands MIP-1alpha and RANTES in the microvasculature, increased BBB leakage and CCR5(+) cells, as well as neuronal loss, inflammation, and gliosis in the hippocampi. Animals given either the bifunctional or the monofunctional vector were largely protected from KA-induced seizures, neuroinflammation, BBB damage, and neuron loss. Brain CCR5 mRNA was reduced. Rats receiving RNAiR5-bearing vectors showed far greater repair responses: increased neuronal proliferation, and decreased production of MIP-1alpha and RANTES. Controls received unrelated SV(BUGT) vectors. Decrease in CCR5 in circulating cells strongly protected from excitotoxin-induced seizures, BBB leakage, CNS injury, and inflammation, and facilitated neurogenic repair.-Louboutin, J.-P., Chekmasova, A., Marusich, E., Agrawal, L., Strayer, D. S. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Seizures  IEP 4889880protein:increased expression:hippocampus and vasculature (rat)RGD 
Experimental Seizures treatmentIMP 4889880 RGD 
visual epilepsy  ISOCcl5 (Rattus norvegicus)4889880; 4889880protein:increased expression:hippocampus and vasculature (rat)RGD 
visual epilepsy  ISOCcr5 (Rattus norvegicus)4889880; 4889880 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neural precursor cell proliferation  IMP 4889880 RGD 
positive regulation of cell killing  IMP 4889880positive regulationRGD 
regulation of cell migration  IMP 4889880 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl5  (C-C motif chemokine ligand 5)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Mus musculus)
Ccl5  (C-C motif chemokine ligand 5)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Homo sapiens)
CCL5  (C-C motif chemokine ligand 5)
CCR5  (C-C motif chemokine receptor 5)


Additional Information