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By Katherine M Woodbury-Harris

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Furthermore, nimodipine has been shown to produce a slight, but significant increase in survival in aneurysmal SAH patients and have been approved in most countries for the treatment of that condition. Indeed, nimodipine represents the first agent to be approved for neuroprotective use even though much of its effect is probably mediated via protection of the microvasculature and vasodilation-mediated improvements in cerebral blood flow. Due to a manifestation of its microvascular vasodilation, the compound must be used with care, since it can lower arterial and cerebral perfusion pressures which can exacerbate posttraumatic, postischemic or post-SAH secondary brain injury.

The target gene in the resulting double transgenic mouse is then induced through administration of a drug [54]. One recent application of this technology involved an examination of the role of vascular endothelial growth factor in regulating brain angiogenesis and neuronal apoptotic cell death [55]. Lastly, it is now possible to develop conditional KO mice in which a gene of interest can be knocked out in a particular cell type such as in astrocytes [56] or endothelial cells [57]. Although there may be some applications of genetically modified mice in drug testing, these technologies are mainly useful for identifying the physiological or pathophysiological role of certain candidate genes and validation of potential neuroprotective or neurorestorative therapeutic targets.

The therapeutic goal is to mitigate this secondary neuronal injury which does not become fully manifest until between 24 and 48 h and perhaps a month after the insult. The most straightforward animal models involve the induction of a human-like cardiac arrest and resuscitation within the next several minutes. Most such studies have been performed in dogs, but rat, mouse and swine models are also utilized. The vast majority of cardiac arrest/resuscitation neurologically focused studies utilize rodent models of transient global cerebral ischemia without stopping and restarting the heart.

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