Inflammatory response and glia activation in developing rat hippocampus after status epilepticus.
OBJECTIVE
We investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid-induced status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats.


METHODS
Limbic seizures were induced by systemic injection of kainic acid. Glia activation and neuronal cell loss were studied by using immunocytochemistry and Western blot. Cytokine expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot quantification.


RESULTS
After SE onset, hippocampal glia activation, cytokine expression, and neuronal damage are all age-dependent phenomena. In the hippocampus, neuronal injury occurs only when cytokines are induced in glia, and cytokine synthesis precedes the appearance of degenerating neurons. Neuronal injury is more pronounced when interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are produced in addition to IL-1beta.


CONCLUSIONS
This study shows that cytokine induction in rat brain after sustained seizures is age dependent, and it is associated with the appearance of cell injury.
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. ravizza@marionegri.it
Teresa
T
Ravizza
Massimo
M
Rizzi
Carlo
C
Perego
Cristina
C
Richichi
Jana
J
Velísková
Solomon L
SL
Moshé
M Grazia
MG
De Simoni
Annamaria
A
Vezzani
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology / Q000502:physiology; D015153:Blotting, Western; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D005911:Gliosis / Q000276:immunology / Q000503:physiopathology; D006624:Hippocampus / Q000254:growth & development* / Q000276:immunology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000276:immunology; D007608:Kainic Acid; D008297:Male; D009410:Nerve Degeneration / Q000276:immunology / Q000503:physiopathology; D009457:Neuroglia / Q000276:immunology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013226:Status Epilepticus / Q000139:chemically induced* / Q000276:immunology* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007608:Kainic Acid