What have genetically engineered mice taught us about ischemic injury?
Stroke, is the third leading cause of death and disability in the Western world. Stroke refers to set of ischemic conditions resulting from the occlusion or hemorrhage of blood vessels supplying the brain. Loss of blood flow to the brain results in neuronal injury due to both oxygen and nutrient deprivation and the activation of injurious signal cascades. Ultimately cerebral ischemia results in death and dysfunction of brain cells, and neurological deficits that reflect the location and size of the compromised brain area. Injury due to ischemic stroke occurs by a highly choreographed series of complex spatial and temporal events that evolve over hours to days. These events involve complex interactions between fundamental cell injury mechanisms including excitotoxicity and ionic imbalance, oxidative and nitrosative stress, apoptotic-like cell death and inflammatory responses. Genetically engineered mice have been valuable tools to probe putative mechanisms of neuronal death and uncover potential strategies that might render neurons resistant to ischemic injury. Findings from experimental stroke studies in genetically engineered animals are discussed.
Liang
Dong
D
Department of Neurology, Johns Hopkins University School of Medicine, 733 North Broadway Street, Suit 731, Baltimore, MD 21205, USA.
Dawson
Ted M
TM
Dawson
Valina L
VL
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000473:pathology*; D002545:Brain Ischemia; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004195:Disease Models, Animal; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D051379:Mice; D008822:Mice, Transgenic; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction
D006133:Growth Substances; D009584:Nitrogen