1. Hypertension and stress: optical imaging of injuries of blood-brain barrier and cerebral blood flow
O. Semyachkina-Glushkovskaya, S. Sindeev, O. Sindeeva, A. Abdurashitov, A. Shirokov, N. Navolokin, A. Gelaluyk, M. Ulanova, V. Razubaeva, V. Fedorova, E. Saranceva, A. Esmat Sharif, V. Tuchin

2. Stress-related hypertension as a main reason of stroke
Hypertension is the most prevalent of risk factors for stroke but the direct role of high blood pressure in stroke development is not generally appreciated due to limitation our knowledge about mechanisms underlying these pathological processes.

3. What happens with experimental rats or in the brain of rats
For the better understanding of mechanisms responsible for the decrease in resistance of cerebral vessels to stroke in hypertensive subjects, here we studied next changes in hypertensive rats:
cerebral blood flow
and
permeability of blood-brain barrier

4. The model of hypertension in experiments with rats
To induce chronic hypertension in rats we used surgical renal hypertension model developed by Goldblatt. To modernize and improve this method we use modified artery clipping procedure and clip itself. The clip were implanted on a left renal artery and then after 7 weeks chronic hypertension were developed.

5. To ensure that experimental animals had a chronic hypertension status we used direct blood pressure measurement. For this we implanted polythene catheter to the left carotid artery and connected it to PowerLab /400 acquisition system (ADInstruments, Australia)

6. What’s happened to experimental rats after surgery?

7. Laser Contrast Speckle Imaging
Achieved Laser Contrast Speckle Imaging data showed that hypertension formation was accompanied by cerebral ischemic events. So, we observed the decrease in CBF in the cortex by 17% (p<0.05) in hypertensive rats compared with healthy animals.

8. Histological assay
The hypertension-related reduction of cerebral bloodflow was associated with morphological signs of ischemia such as:
- the appearance of shade cells with indistinct contours
- apoptotic bodies
- decreased quantity of neural cells.

9. Blood-brain barrier permeability test
The increased blood-brain barrier (BBB) permeability is discussed as one of reasons for the stroke in hypertensive subjects. To test this fact in the next step of our work we analyzed the BBB permeability in rats with high blood pressure. The BBB was impermeable for dextran and gadolinium in hypertensive rats (fig. A1 and A2).

10. Blood-brain barrier permeability test
Since stress is a potential provoking factor for stroke, in the final step of experiments we analyzed the effect of sound stress on the cerebral vessels in hypertensive rats and evaluated the BBB permeability. Our results showed that all hypertensive rats demonstrated the intracranial hemorrhages in the area of cerebellum and the increasing of BBB permeability to dextran and gadolinium (contrasted areas showed by red arrows).

11. Conclusion
In summary, we concluded that high blood pressure itself does not cause stroke but significantly decreases the adaptive capacity of cerebral vessels to stress. The stress is provoking factor for stroke in hypertensive rats. The deleterious stress effects on the vascular homeostasis on the level of microcirculation and cerebral endothelium might be a key reason for a risk of stroke in hypertensive subjects. This work is supported by Grant of Russian Science Foundation №

12. Thanks for your attention!