MORPHOLOGICAL AND FUNCTIONAL CHARACTERISTICS OF THE MICROVASCULATURE AND NEURONS IN NEOCORTEX AFTER ISCHEMIC POSTCONDITIONING

Abstract

PECAM-1/CD31 (biomarker of endothelial function and neovascularization) was used to assess protein expression in microvessels of cortical layers II, III and V in Mongolian gerbils ( Meriones unguiculatus ) in the early (Day 2) and late (Day 7) reperfusion period after a 7-minute forebrain ischemia and subsequent ischemic postconditioning (IPostC), as well as in sham-operated animals (n=60). The latter demonstrated the lowest level of immunoreactivity to PECAM-1/CD31 in the structures in cortical layer III. Reversible ischemic brain damage manifested itself in the reduction of number of morphologically unchanged neocortical neurons and extension of the reperfusion period; in addition to that, an increase in the level of immunoreactivity to PECAM-1/CD31 was observed in layers II, III and V of the cortex and it was significantly augmented towards the late reperfusion period. IPostC, performed by three stimulating cycles of ischemia-reperfusion lasting 15/15 seconds, resulted in a significant increase in the number of morphologically unchanged neurons in cortical layers II and III in the early reperfusion period. In the late reperfusion period, after IPostC, the number of unchanged neurons in layers II, III and V of the cortex was increased, while the level of immunoreactivity for PECAM-1/CD31 in these structures was significantly decreased. These results allow to conclude that the cytoprotective effect of IPostC under ischemia was implemented through the physiological mechanism of adaptation, which enhanced immunoreactivity for PECAM-1/CD31 in microvessels of the cerebral cortex in the early reperfusion period, and inhibited it in the late reperfusion period.

Keywords

neocortex / neurons / PECAM-1/CD31 / ischemiareperfusion / ischemic postconditioning

References

[1] Адрианов О. С. О принципах структурно-функциональной организации мозга (избранные труды). М.: Медицина, 1999.

[2] Щербак Н. С., Русакова А. Г., Галагудза М. М. и др. Изменение экспрессии белка Bcl2 в нейронах полей гиппокампа после применения ишемического посткондиционирования головного мозга // Морфология. 2015. Т. 148, вып. 5. С. 21-27.

[3] Agnić I., Vukojević K., Saraga-Babić M. et al. Isoflurane post-conditioning stimulates the proliferative phase of myocardial recovery in an ischemia-reperfusion model of heart injury in rats // Histol. Histopathol. 2014. Vol. 29, № 1. Р. 89-99.

[4] Deddens L. H., van Tilborg G. A., van der Toorn A. et al. PECAM-1-targeted micron-sized particles of iron oxide as MRI contrast agent for detection of vascular remodeling after cerebral ischemia // Contrast Media Mol. Imaging. 2013. Vol. 8, № 5. Р. 393-401.

[5] Ding Z. M., Wu B., Zhang W. Q. et al. Neuroprotective effects of ischemic preconditioning and postconditioning on global brain ischemia in rats through the same effect on inhibition of apoptosis // Int. J. Mol. Sci. 2012. Vol. 13, № 5. Р. 6089-6101.

[6] Hwang I. K., Kim D. W., Yoo K. Y. et al. Ischemia-induced changes of platelet endothelial cell adhesion molecule-1 in the hippocampal CA1 region in gerbils // Brain. Res. 2005. Vol. 1048, № 1-2. Р. 251-257.

[7] Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia // Brain Res. 1982. Vol. 239. Р. 57-69.

[8] Loskota W.J., Lomax P., Verity M. A. A Stereotaxic Atlas of the Mongolian Gerbil Brain // Ann Arbor, Mich. USA. Ann Arbor Sci. Publishers, 1974.

[9] Marti H. J., Bernaudin M., Bellail A. et al. Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia // Am. J. Pathol. 2000. Vol. 156, № 3. Р. 965-976.

[10] Matsuda F., Sakakima H., Yoshida Y. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats // Acta. Physiol (Oxf.). 2011. Vol. 201, № 2. Р. 275-287.

[11] Mora-Lee S., Sirerol-Piquer M. S., Gutierrez-Perez M. et al. Histo logical and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice // J. Inflamm. 2011. Vol. 8, № 1. Р. 28-33.

[12] Newman P. J. Respective series: cell adhesion in vascular biology // J. Clin. Invest. 1997. Vol. 100. P. 25-29.

[13] Otsuka S., Sakakima H., Sumizono M. et al. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats // Behav. Brain Res. 2016. Vol. 303. Р. 9-18.

[14] Park S., DiMaio T.A., Scheef E. A. et al. PECAM-1 regulates proangiogenic properties of endothelial cells through modulation of cell-cell and cell-matrix interactions // Am. J. Physiol. Cell Physiol. 2010. Vol. 299. Р. 1468-1484.

[15] Pulsinelli W.A., Buchan A. M. The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation // Stroke. 1988. Vol. 19. Р. 913-914.

[16] Stummer W., Weber K., Tranmer B. et al. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia // Stroke. 1994. Vol. 25. Р. 1862-1869.

RIGHTS & PERMISSIONS

Eco-Vector