[The involvement of cytokines, chemokines and inducible nitric oxide synthase (iNOS) induced by a transient ischemia in neuronal survival/death in rat brain].
Inflammatory/immunological processes underlie the survival/damage of neurons after brain ischemia. In glial cells, cytokines such as IL-1 beta and TNF-alpha are produced following ischemic stresses. On the other hand, it is suggested that NO/iNOS is involved in neuronal apoptosis. We here review the ischemia-induced production of cytokine/iNOS and the neurotrophic/neurotoxic effects. It is not clear whether or not the neuronal death after brain ischemia is apoptosis or necrosis. Under the condition of transient forebrain ischemia, however, we obtained results suggesting apoptosis in the delayed neuronal death of the CA1 pyramidal neurons. The time course and cellular localization of postischemic iNOS expression depend on the properties of the ischemic insult. The iNOS induction is detected primarily in astrocytes after the transient forebrain ischemia when the neuronal apoptosis is observed. We discuss a variety of cytokines with neurotrophic/neurotoxic actions that are produced by ischemia or environmental stresses in glial cells. From the neurotoxicological aspect of the neuro-glial interaction, we also review recent findings on signalling pathways of the iNOS induction in glial cells and the mechanisms of the cytotoxic actions of NO.
Okuma
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Uehara
T
T
Miyazaki
H
H
Miyasaka
T
T
Nomura
Y
Y
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000201:enzymology; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D018925:Chemokines / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats
D018925:Chemokines; D016207:Cytokines; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat