Increase in omega 3 (peripheral type benzodiazepine) binding sites in the rat cortex and striatum after local injection of interleukin-1, tumour necrosis factor-alpha and lipopolysaccharide.
The possible involvement of lymphokines in the glial reaction/proliferation that follows brain injury has been investigated by measuring the density of omega 3 (peripheral type benzodiazepine) binding sites associated to glial cells and macrophages after local injection of lymphokines in the rat cerebral cortex and striatum. omega 3 Site densities were measured either by quantitative autoradiography in brain sections or by conventional binding in membrane using [3H]PK 14105 or [3H]PK 11195 as ligands. Intracortical or intrastriatal infusion of interleukin-1 (10 and 20 units) caused a marked increase in the density of omega 3 sites (+83% and +80%, respectively, when compared to saline-infused animals) around the injection site at 7 days postinjection. There was a good spatial correspondence between the autoradiographic distribution of omega 3 sites and the distribution of reactive astrocytes (as assessed by GFAP immunostaining) or acid phosphatase rich cells (phagocytes). Significant increases in omega 3 site densities were also observed in striatal homogenates 1 week after local administration of tumor necrosis factor-alpha (TNF-alpha). The maximal increase (+80%) was observed after the administration of 3 units, higher and lower doses resulting in smaller increases. Intrastriatal injection of E. coli lipopolysaccharide (LPS), a bacterial endotoxin known to stimulate interleukin-1 and TNF-alpha production by microglial cells in culture, also resulted in significant increases in omega 3 site densities in striatal homogenates (maximal increase, +170% 1 week after the injection of 200 ng).(ABSTRACT TRUNCATED AT 250 WORDS)
Bourdiol
F
F
Biology Department, Synthélabo Recherche, Bagneux, France.
Toulmond
S
S
Serrano
A
A
Benavides
J
J
Scatton
B
B
D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005442:Flumazenil / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D013238:Stereotaxic Techniques; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011963:Receptors, GABA-A; D014409:Tumor Necrosis Factor-alpha; D005442:Flumazenil; D009240:N-Formylmethionine Leucyl-Phenylalanine