Cerebral ischemia focal models

Singhal AB, Wang X, Sumii T, Mori T, Lo EH. Effects of normobaric h3fperoxia in a rat model of focal cerebral ischemia-reperfusion. J Cereb Blood Flow Metab 2002 22 861 868. 

O Neill, M., Rodent models of focal cerebral ischemia, in Current Protocols in Neuroscience, Crawley, J., Gerfen C., Rogawski, M., Sibley, D., Skolnick, P. and Wray, S., Eds., Wiley, New York, 1998, chap. 9. 

Bao, W. L., Williams, A. J., Faden, A. I., and Tortella, F. C. (2001). Selective mGluR5 receptor antagonist or agonist provides neuroprotection in a rat model of focal cerebral ischemia. Brain Res. 922, 173-179. 

In states of focal cerebral ischemia, repetitive MRI has elucidated the natural course of brain lesions which - as a regular phenomenon - show considerable lesion enlargement over time. This observation was made by using DWI in animal models with occlusion of the middle cerebral artery. To date, we have little information on the natural course of ischemic lesions that are of hemodynamic origin or the result... 

Zhang RL, Chopp M, Zhang ZG, Jiang Q, Ewing JR (1997) A rat model of focal embolic cerebral ischemia. Brain Res 766 83-92... 

During cerebral ischemia, water proton mobility declines rapidly, which may be measured with diffusion-weighted imaging (DWI) or other methods (Nicholson and Sykova 1998). In animal models of focal ischemia, the ADC declines by about 30%-50% starting within a few minutes following onset... 

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)...

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. 

Zausinger S., Westermaier T., Baethmann A., Steiger H. J., and Schmid-Elsaesser R. (2001) Neuroprotective treatment paradigms in neurovascular surgery—efficacy in a rat model of focal cerebral ischemia. Acta Neurochir. Suppl. 77, 259-265. 

It is known from animal models with global ischemia and traumatic brain injury that moderate hypothermia attenuates secondary brain damage by reducing cerebral ischemia and postischemic brain edema and preserving the blood-brainbarrier. Even though hypothermia has potent cerebroprotective effects after experimental focal ischemia, clinical studies on hypothermic therapy after MCA infarction were not available until recently. We performed a pilot study investigating the efficacy, feasibility, and safety of induced moderate hypothermia in the therapy of patients with acute, severe MCA infarction and increased ICP. 

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. 

Lorenzl S, Kodel U, Frei K, Pfister HW (1996) Effect of the bradykinin B2 receptor antagonist Hoel40 in experimental pneumococcal meningitis in the rat. Eur J Pharmacol 308 335-341 Lumenta DB, Plesnila N, Klasner B, Baethmann A, Pruneau D, Schmid-Elsaesser R, Zausinger S (2006) Neuroprotective effects of a postischemic treatment with a bradykinin B2 receptor antagonist in a rat model of temporary focal cerebral ischemia. Brain Res 1069 227-234 Mac Donald CL, Dikranian K, Bayly P, Holtzman D, Brody D (2(X)7) Diffusion tensor imaging reliably detects experimental traumatic axonal injury and indicates approximate time of injury. J Neurosci 27 11869-11876... 

Zausinger S, Lumenta DB, Pruneau D, Schmid-Elsaesser R, Plesnila N, Baethmann A (2002) Effects of LF 16-0687 Ms, a bradyMnin B(2) receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia. Brain Res 950 268-278... 

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