[Targets of treatment in the acute phase of cerebral infarction].
In the acute phase of cerebral infarction, many experimental data suggest that free radicals including superoxide, hydroxy radical and nitric oxide are one of the most important factors to cause brain damage. We have clearly detected nitrotyrosine (a marker of endogenous production of peroxynitrite, which is readily produced from superoxide and nitric oxide) in neurons and intraparenchymal vascular walls during post-ischemic reperfusion. Free radical scavengers thus seem to be very promising tools of treatment, and one of them (edaravone) has recently been approved for clinical use in Japan. CREB (cyclic AMP response element binding protein) is a DNA-binding transcription factor, and its function is activated by phosphorylation of Ser133 residue. CREB plays important roles in neuronal development, synaptic plasticity and regeneration. We have found that phosphorylation of CREB is significantly and persistently increased in surviving neurons and oligodendrocytes in post-ischemic brain, while this phosphorylation is only transiently increased in neurons and oligodendrocytes which eventually die. These data suggest that CREB phosphorylation plays an important role in protection of ischemic brain tissue. Oligodendrocyte progenitor cells (OPC) remain abundant throughout the adult brain, and retain their ability to become not only mature oligodendrocytes, but also neurons. We have recently found that OPC are significantly activated and proliferate in the peri-infarct area at 1-2 weeks after ischemia, suggesting that OPC may be involved in the repair mechanisms of ischemic brain. Future targets of stroke treatment should include enhancement of intrinsic protection mechanisms such as CREB phosphorylation and activation of progenitors cells.
Tanaka
K
K
Department of Neurology, School of Medicine, Keio University.
Fukuuchi
Y
Y
Nogawa
S
S
Ito
D
D
Suzuki
S
S
Dembo
T
T
Kosakai
A
A
D000210:Acute-Phase Reaction; D002544:Cerebral Infarction / Q000628:therapy*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D005609:Free Radicals; D006801:Humans; D009836:Oligodendroglia; D010766:Phosphorylation; D013234:Stem Cells
D017362:Cyclic AMP Response Element-Binding Protein; D016166:Free Radical Scavengers; D005609:Free Radicals