[Molecular mechanism of ischemic brain injuries and perspectives of drug therapies for neuroprotection].
Ischemic brain injury is a critical condition in the management of patients during anesthesia and intensive care. It is not rare that pathological conditions such as cerebral ischemia, head trauma and low oxygen result in marked impairment of cerebral function, even if the patient's life is saved. We sometimes encounter sudden changes in a patient's condition not only during anesthesia, but also in intensive care unit with transient low-oxygen and ischemic conditions accompanying serious shock. We have been studying the mechanisms to counteract pathological conditions leading to neuronal cell death that have been exposed to such emergency conditions, and to discover therapeutic methods to minimize the brain damage after insult. With advances in the understanding of the mechanism of neuronal cell death, technology in intensive care for salvaging neuronal cell that are at the brink of death and for recovery of brain function has progressed. However, a breakthrough has not been achieved in the development of effective therapy. Protection of the brain from terminal impairment and preservation of function will be an important issue. To achieve this goal, it is critical to clarify the susceptible mechanisms causing ischemic brain damage. This report discusses the importance of the calcineurin/immunophilin signal transduction mechanism as a new mechanism that is involved in the induction of ischemic brain damage and refers the status-quo of cerebral protection by drug therapy.
Uchino
Hiroyuki
H
Department of Anesthesiology, Hachioji Medical Center, Tokyo Medical University, Hachioji.
Morota
Saori
S
Hirabayashi
Go
G
Ushijima
Kazuo
K
Kakinuma
Takayasu
T
Ishii
Nagao
N
Shibasaki
Futoshi
F
Kuroda
Yasuhiro
Y
D000777:Anesthetics / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D019703:Calcineurin / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early / Q000502:physiology; D015316:Genetic Therapy; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D020104:Immunophilins / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
D000777:Anesthetics; D015815:Cell Adhesion Molecules; D016207:Cytokines; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D024683:Potassium Channels, Tandem Pore Domain; D011506:Proteins; C103742:potassium channel protein TREK-1; D018698:Glutamic Acid; D019703:Calcineurin; D020104:Immunophilins; D002118:Calcium