Dynamic induction of the long pentraxin PTX3 in the CNS after limbic seizures: evidence for a protective role in seizure-induced neurodegeneration.
Pentraxin 3, a prototypic long pentraxin, is induced by proinflammatory signals in the brain. Inflammatory cytokines are rapidly induced in glia by epileptic activity. We show that pentraxin 3 immunoreactivity and mRNA are enhanced in the rat forebrain above undetectable control levels by limbic seizures with a dual pattern of induction. Within 6 h from seizure onset, pentraxin 3 immunoreactivity was increased in astrocytes. Eighteen to 48 h later, specific neuronal populations and leucocytes were strongly immunoreactive only in areas of neurodegeneration. This staining was abolished when neuronal cell loss, but not seizures, was prevented by blocking N-methyl-D-aspartate receptors. Pentraxin 3 -/- mice had a more widespread seizure-related neuronal damage in the forebrain than their wild-type littermates although both groups had similar epileptic activity. Our results provide evidence that pentraxin 3 is synthesized in brain after seizures and may exert a protective role in seizure-induced neurodegeneration.
Ravizza
T
T
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy.
Moneta
D
D
Bottazzi
B
B
Peri
G
G
Garlanda
C
C
Hirsch
E
E
Richards
G J
GJ
Mantovani
A
A
Vezzani
A
A
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D008032:Limbic System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D000099153:Pentraxins
D015763:2-Amino-5-phosphonovalerate; D002097:C-Reactive Protein; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D007608:Kainic Acid; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid