Transient cerebral ischemia model

Especially in models of transient cerebral ischemia, apoptotic cell death has been observed after 3-7 days post insult in selected brain regions in which basal energy metabolism has been preserved (Chen et al. 1997 Du et al. 1996). In the meantime, molecular switches have been identified that gate different populations of neurons with regard to the type of cell death they eventually undergo (Nicotera 2003). However, there is little doubt that in animal stroke the vast majority of cells would die from necrosis or, alternatively, secondary energy failure even in the presence of a pro-apop-totic genetic balance. The concept of thresholds of cerebral blood flow (CBF) for various functions of brain parenchyma (see below) explains why the infarct core suffers from pan-necrosis whereas the peri-infarct border in which function is suppressed, but structure initially preserved (the so-called ischemic penumbra), may show apoptotic cell death or a combination of both. 

A number of animal models have been developed to mimic cerebral ischemia experimentally. They can be roughly categorized into global (bilateral arterial occlusion) and focal (unilateral arterial occlusion) cerebral ischemia models. Probably the widest applied method is the middle cerebral artery occlusion (MCAO), performed by transiently blocking the arterial blood flow with a removable thread or... 

Maier C. M., Ahem K., Cheng M. L., Lee J. E., Yenari M. A., and Steinberg G. K. (1998) Optimal depth and duration of mild hypothermia in a focal model of transient cerebral ischemia effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke 29, 2171-2180. 

There is some evidence, however, that the potential utility of a tHb as a hemodiluent and tissue-oxygenating solution may be dependent on the structure and properties of that tHb. For example, the results of a study of the effects of partial blood replacement with pyridoxa-lated Hb polyoxyethylene conjugate (PHP) solution (Ajinomoto) in a gerbil model of transient cerebral ischemia suggested that PHP solution holds less promise as a clinical treatment for this type of focal ischemia than does DCLHb.t ]... 

Yin W, Badr AE, Mychaskiw G, Zhang JH. Down regulation of cox-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model. Brain Res. 2002 926 165-171... 

An early in vivo study in the model of global forebrain ischemia in the gerbil showed that a selective agonist of A3AR, IB-MECA, acutely administered 15 min prior to ischemia, impaired post-ischemic blood flow, increased mortality and exacerbated the loss of hippocampal neurons (von Lubitz et al. 1994). IB-MECA administration 20 min prior to transient middle cerebral ischemia also resulted in a significant increase in infarct size(von Lubitz et al. 2001). 

Fig. 7.7. Transient ADC recovery and secondary ADC decline. Time course of ADC changes in a rat model of focal cerebral ischemia, as shown in two examples (30-min and 150-min suture occlusion). After 30 min of ischemia both DWI and ADC changes resolve during the early reperfusion period. This is followed by evolution of a secondary DWI abnormality at day 1 following ischemia, which is associated with a lesion seen on T2-weighted imaging. In contrast, no resolution of DWI or ADC changes is observed following 150-min occlusion (see lower part of the image). (The data were acquired in collaboration with A. Kastrup, A. de Crespigny and M.E. Moseley, Stanford University)...

The mechanism of delayed neuronal injury following TBI includes apoptosis (63,64). Experimental data after cerebral hypoxic-ischemic injury indicate that moderate postinsult hypothermia (34°C) reduced the fraction of apoptotic cells but not cells undergoing necrosis (65). In another study, intraischemic hypothermia reduced the number of transferase dUTP nick-end labeling (TUNEL)-positive cells after transient focal ischemia (66). Thus, it will be important in future studies to determine whether hypothermia inhibits apoptotic neuronal cell death in models of TBI. 

AIF may contribute to acute neuronal injury induced by trauma, hypoglycemia or transient ischemia as well as in chronic neurodegeneradve diseases (Table 3). The translocadon of AIF has been observed in different experimental models of neurotoxicity including death of photoreceptors induced by rednal detachment, neuronal cell death induct in vivo by brain trauma and cerebral ischemia and death of cortical neurons induced in vitro by exposure to... 

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