Focal cerebral ischemia studies

Dijkhuizen RM, Singhal AB, Mandeville JB, Wu O, Halpern EF, Finklestein SP, Rosen BR, Lo EH (2003) Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats a functional magnetic resonance imaging study. J Neurosci 23 510-517... 

The concept of neuroprotection relies on the fact that delayed neuronal injury occurs after ischemia, and each step along the ischemic cascade provides a target for therapeutic intervention. Thus, understanding the cellular and molecular mechanisms that underlie the development of neuronal and vascular injury is critical to optimize treatment. This chapter reviews experimental evidence from studies on focal cerebral ischemia and mild hypothermia, as well as the mechanisms involved in mild hypothermic neuroprotection. 

We recently carried out a study (40) to determine the effects of delaying induction of mild hypothermia after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over... 

Kollmar R., Schabitz W. R., Heiland S., et al. (2002) Neuroprotective effect of delayed moderate hypothermia after focal cerebral ischemia an MRI study. Stroke 33, 1899-1904. 

KEY STUDIES OF DELAYED HYPOTHERMIA IN FOCAL CEREBRAL ISCHEMIA... 

The middle cerebral artery occlusion model (MCAO) is commonly used in experimental focal cerebral ischemia. This technique causes hypothalamic injury resulting in hyperthermia, worsening outcome and possibly masking neuroprotective effects. Thus, careful temperature monitoring is needed in those preclinical studies. Recently, Gerriets et al. (10) introduced a new MCAO model that involves intraarterial embolizationusing macrospheres. Unlike the traditional MCAO suture model, this macrosphere model does not result in hyperthermia and yet provides reproducible infarcts. 

In addition to small molecules, a number of protein therapeutic agents, such as neurotrophic factors27 and insulin,28 have been successfully delivered to the CNS using IN delivery in a variety of species. The therapeutic benefit of IN delivery of proteins has been demonstrated by Liu et al. in rat stroke models.29 Their studies demonstrated that insulin-like growth factor I (IGF-I) could be delivered to the brain directly from the nasal cavity, even though IGF-I did not cross the BBB efficiently by itself. As a consequence, IN IGF-I markedly reduced infarct volume and improved neurological function following focal cerebral ischemia. Research in... 

Ionotropic glutamate receptors also promote perturbations in ionic homeostasis that play a critical role in cerebral ischemia. For example, L, P/Q, and N-type calcium channel receptors mediate excessive calcium influx, and Ca " channel antagonists reduce ischemic brain injury in preclinical studies [12-14]. Zinc is stored in vesicles of excitatory neurons and coreleased upon depolarization after focal cerebral ischemia, resulting in neuronal death [15, 16]. Recently, imbalances in potassium have also been implicated in ischemic cell death. Compounds that selectively modulate a class of calcium-sensitive high conduc-tance potassium (maxi-K) channels protect brain against stroke in animal models [17]. 

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