Three-dimensional structure and survival of newly formed blood vessels after focal cerebral ischemia

Abstract

Penumbra tissue becomes highly angiogenic after ischaemic stroke in man, and the re-establishment of a functional vasculature might be beneficial to patients. Unilateral ischaemia was induced in male Sprague-Dawley rats by permanent occlusion of the distal left middle cerebral artery (MCAO). Animals with stroke were kept alive for 1, 7, 14, 21 or 28 days after which time they were terminally anaesthetized. Vascular casts of infarcted areas, analyzed by scanning electron microscopy demonstrated that radially arranged neocortical arterioles and venules lost their regular patterns within one day of occlusion, and soon afterwards started to form a very dense network of anastomosing microvessels. At 1 week, vascular budding was visible at many sites. The smallest microvessels (4-10 microm) formed connections with the surrounding proliferating vessels similar to those in the normal brain. Survival of microvascular endothelial cells (ECs) was studied by double labeling of tissue sections using immunohistochemistry and antibodies to caspase-3, and TUNEL staining for apoptotic cells. ECs demonstrated intensive staining for caspase-3 and also staining by TUNEL, particularly near the infarct border, 14 days post-MCAO. These data support the hypothesis that growing blood vessels in ischaemic tissue form new connections, the pattern of which is similar to that in normal rat brain, but different to those formed in growing tumours. This normal growth pattern might be essential in future therapies involving induction of vascularization and neuroprotection to enhance long-term survival of the penumbra.

Correlation of CD34+ cells with Tissue Angiogenesis after Traumatic Brain Injury in a Rat Model

“…Our finding is also consistent with early reports that CD34 þ cells selectively homed to the sites of angiogenesis, become fully integrated in the microvascular endothelium, and differentiate into mature endothelial cells (Krupinski et al, 2003;Morris et al, 2003). In addition to physical lining of vessel wall, the new endothelial cells have a significant stimulatory effect on the formation of new capillary (Zhang et al, 2002;Morris et al, 2003;Rookmaaker et al, 2005).…”

“…The cells eventually home to the site of injured tissue (Beck et al, 2003;Assmus et al, 2006) to initiate and propagate angiogenesis (Krupinski et al, 2003;Morris et al, 2003). As a result, the levels of CD34 þ cells in peripheral blood and injured tissue could be considered to reliably indicate the rate and extent of tissue repair.…”

Mechanisms and targets for angiogenic therapy after stroke

“…30,31 Hence, VEGF monotherapy has garnered much attention as a formidable therapeutic avenue after stroke. [32][33][34] One of the first studies of VEGF in ischemic stroke showed that mRNA and protein of VEGF 165 VEGF 189 and the receptor flk-1 were found to be upregulated in human post-mortem brain. 35 In rodent models of stroke, an intra-cerebroventricular injection of VEGF via osmotic pump, starting 24 hours after onset of focal cerebral ischemia, the stimulation of angiogenesis coincided with a reduction of infarct volume.…”

Angiogenic activity of latex from Euphorbia tirucalliLinnaeus 1753 (Plantae, Euphorbiaceae)

“…To date, diverse studies have been conducted with the aim of finding substances that can induce angiogenesis, since the possibilities of clinical application of these substances in myocardial vascularity and the central nervous system are extensive, after injury or ischemia, partial replacement of large arteries, and even in wound healing (Krupinski et al, 2003;Slevin et al, 2005).…”