TY - JOUR
T1 - Glia activation and cytokine increase in rat hippocampus by kainic acid-induced status epilepticus during postnatal development
AU - Rizzi, Massimo
AU - Perego, Carlo
AU - Aliprandi, Marisa
AU - Richichi, Cristina
AU - Ravizza, Teresa
AU - Colella, Daniele
AU - Velískǒvá, Jana
AU - Moshé, Solomon L.
AU - De Simoni, M. Grazia
AU - Vezzani, Annamaria
N1 - Funding Information:
We thank Ms Daniela Moneta for her contribution to this study. This work was supported by CURE, Fondazione Mariani Onlus, the Heffer Family Foundation (AV), and Grants NS-36238 (JV) and NS-20253 (SLM) from the NINDS. SLM is the recipient of the Martin A. and Emily L. Fisher fellowship in Neurology and Pediatrics. MA is the recipient of the F.B. 2001 fellowship.
PY - 2003/12
Y1 - 2003/12
N2 - In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1β (IL), tumor necrosis factor-α (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1β mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage.
AB - In adult rats, status epilepticus (SE) induces cytokine production by glia especially when seizures are associated with neuronal injury. This suggests that cytokines may play a role in seizure-induced neuronal damage. As SE-induced injury is age-specific, we used rats of different ages (with distinct susceptibilities to seizure-induced neuronal injury) to elucidate the role of cytokines in this process. Thus, we investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal injury 4 and 24 h following kainic acid-induced SE in postnatal day (PN) 9, 15, and 21 rats. At PN9, there was little activation of microglia and astrocytes at any time point studied. Interleukin-1β (IL), tumor necrosis factor-α (TNF), and IL-6 or the naturally occurring IL-1 receptor antagonist (Ra) mRNA expression did not increase. No evidence of cell injury has been detected. At PN15, immunostaining of microglia and astrocytes was enhanced, but only IL-1β mRNA expression was increased. These changes were observed 4 h after SE. Scattered injured neurons in CA3 and subiculum, but not in any other region, were present 24 h following SE. At PN21, immunostaining of microglia and astrocytes and the mRNA expression of all cytokines studied was significantly increased already 4 h after SE. At 24 h, many injured neurons were present in CA1 and CA3 regions and in 40% of rats in other forebrain areas. These data show that (i) the pattern of glia activation and cytokine gene transcription induced by SE is age-dependent and (ii) neuronal injury in the hippocampus occurs only when cytokines are induced and their synthesis precedes the appearance of neuronal damage. Thus, cytokine expression in immature brain is associated specifically with cell injury rather than with seizures per se, suggesting that proinflammatory cytokines may contribute to the occurence of SE-induced hippocampal damage.
KW - Brain development
KW - Inflammation
KW - Interleukins
KW - Neurodegeneration
KW - TNF-α
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U2 - 10.1016/j.nbd.2003.08.001
DO - 10.1016/j.nbd.2003.08.001
M3 - Article
C2 - 14678765
AN - SCOPUS:10744232929
SN - 0969-9961
VL - 14
SP - 494
EP - 503
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -