New Vessels after Stroke: Postischemic Neovascularization and Regeneration

Abstract

The formation of new blood vessels after acute ischemic stroke is one of the most promising approaches to future therapies in the emerging field of stroke medicine. Angiogenesis and postnatal vasculogenesis are the underlying mechanisms of the formation of new blood vessels. Bone marrow-derived endothelial progenitor cells (EPCs) are thought to play an important role in neovascularization and during the regenerative processes after a vascular injury as well as in the maintenance of endothelial integrity. This review summarizes possible mechanisms of angiogenesis, postischemic neovascularization and regeneration with a focus on the potential role of EPCs as a risk marker and as a therapeutic target in stroke medicine.

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

“…Migrating neuroblasts pass through areas of vascular remodeling and regeneration, suggesting that angiogenesis assists neurogenesis, and that both processes promote functional recovery after ischemic stroke. Taken together, angiogenesis helps to restore neuronal function after ischemic stroke, which may offer useful insights into new treatment approaches for the condition [62,68,69] .…”

Effect of transplantation of cell suspension from embryonic nervous tissue and bone marrow on postischemic cerebral angiogenesis and restoration of limb motor function in rats with experimental ischemic stroke

“…It has been proved that the development of collateral blood flow and functioning of the newly formed vessels in the brain perifocal zone after ischemic injury has a neuroprotective effect, promotes activation of neurogenesis in the subventricular zone of the lateral ventricles and the formation of new neural networks through trophic support within the so-called "neurovascular niche" [20]. In our study, using the CD34 immunohistochemical marker for endotheliocytes and EPCs detection in the newly formed blood vessels, angiogenic effect of tissue transplantation is observed on the 7 th day and reaches its maximum on 28 th day, which, according to some data, corresponds to the period of formation of a stable vascular network functioning [3,31].…”

“…[14,24]. This marker is also expressed by EPCs, which, according to various sources, are actively involved in post-stroke angiogenesis [20,31]. Thus, the definition of the CD34 expression allows us to identify not only endothelial cells, but EPCs in the wall of newly formed vessels that quantitatively demonstrates the activity of neoangiogenesis.…”

“…EPCs from bone marrow can directly differentiate into endotheliocytes of newly formed blood vessels [31]. Restoration of microcirculation and perfusion in PIZ leads to the improvement of local metabolism in the ischemic area and thereby promotes survival of penumbra cells [20].…”

“…There was shown BM MSCs ability to lower levels of inhibitory glycoproteins, which in its turn facilitate the sprouting of axons, and stimulate the production of neurotrophic factors by astrocytes, which are actively involved in the remodeling of the white matter of the brain [19]. Activated astrocytes can express angiogenic factors that contribute to the formation of a neurovascular «niche», which is the epicenter of the tissue reorganization, formation of new synaptic contacts and chemoattraction of endogenous neuroblasts from SVZ [20]. Recovery of motor function may also be associated with remodeling of the corticospinal tract at the level of the spinal cord at experimental stroke using BM MSCs [26].…”