DCS EH-36SS Uživatelský manuál stáhnout pdf (Strana 111)

VII. Summary

Stroke is the third leading cause of death followed by ischemic heart disease and

cancer and the leading cause of adult disability in the industrialized world. Animal

studies serve as an important link between basic research and clinical application of

emerging new neuroprotective treatments. Animal models for the induction of focal

cerebral ischemia should imitate the disease pattern of stroke-patients as close as

possible in order to improve transferability of the results to human stroke. Amongst

several endovascular and non-endovascular rat stroke models available, the

intraluminal suture technique is the most widely used method. One major

disadvantage of this technique is the induction of hypothalamic injury that leads to

disturbances of thermoregulation following stroke induction. This phenomenon is

unknown in humans and can confound the results of animal studies. Recently, the

“macrosphere model” was developed to avoid these side-effects.

Aim of the present study was to evaluate and improve this new technique and to

characterize possible advantages and disadvantages in comparison to established

stroke-models.

In the first experiment the neuroprotective effect of Dizocilpin (MK-801) was

compared to placebo using three different permanent middle cerebral artery

occlusion models. Using the suture-technique, hypothalamic injury occurred in all

animals, which was accompanied by a significant increase in body temperature. This

side-effect was avoided by using the macrosphere-model. Compared to placebo,

Dizocilpin-treatment led to a significant reduction of infarct size (60%) in the

macrosphere-group, whereas no significant neuroprotective effect could be

demonstrated in the suture-group. In order to ensure that the failure of Dizocilpin-

treatment in the suture-group is caused by induction of hypothalamic injury and

pathological hyperthermia not potentially by differences in the operation-techniques,

the macrosphere model was modified by increasing the number of spheres. This

modification led to an occlusion of hypothalamic artery similar to the suture-model.

Consequently, the animals developed hypothalamic injury and subsequent

hyperthermia. As expected, Dizocilpin provided no significant neuroprotective effect

in this group.

These results provide evidence that the induction of hypothalamic damage with

subsequent pathological hyperthermia can obscure the effects of neuroprotective

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DCS EH-36SS Uživatelský manuál Strana 111