Long-Term Remodeling of Rat Pial Microcirculation after Transient Middle Cerebral Artery Occlusion and Reperfusion

Abstract

Objective: The aim of this study was to assess the in vivo structural and functional remodeling of pial arteriolar networks in the ischemic area of rats submitted to transient middle cerebral artery occlusion (MCAO) and different time intervals of reperfusion. Methods and Results: Two closed cranial windows were implanted above the left and right parietal cortex to observe pial microcirculation by fluorescence microscopy. The geometric characteristics of pial arteriolar networks, permeability increase, leukocyte adhesion and capillary density were analyzed after 1 h or 1, 7, 14 or 28 days of reperfusion. MCAO and 1-hour reperfusion caused marked microvascular changes in pial networks. The necrotic core was devoid of vessels, while the penumbra area presented a few arterioles, capillaries and venules with severe neuronal damage. Penumbra microvascular permeability and leukocyte adhesion were pronounced. At 7 days of reperfusion, new pial arterioles were organized in anastomotic vessels, overlapping the ischemic core and in penetrating pial arterioles. Vascular remodeling caused different arteriolar rearrangement up to 28 days of reperfusion and animals gradually regained their motor and sensory functions. Conclusions: Transient MCAO-induced pial-network remodeling is characterized by arteriolar anastomotic arcades. Remodeling mechanisms appear to be accompanied by an increased expression of nitric oxide synthases.

Effects of bone marrow mesenchymal stem cells (BM-MSCs) on rat pial microvascular remodeling after transient middle cerebral artery occlusion

“…Supporting our previous data (Golanov et al, 1994 ; Lapi et al, 2013 ), VEGF, the most important mitogen in the process of angiogenesis, promotes the vascular remodeling. Our results indicated that BM-MSCs increase the expression of this protein and induce other protein expression, playing an important role in the remodeling mechanisms.…”

“…Pial microcirculation remodeling improves neurological outcome after middle cerebral artery occlusion (MCAO), accompanied by higher expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), modulating in vivo angiogenesis, as previously observed (Li et al, 2002 ; Lapi et al, 2008 , 2013 ; Komatsu et al, 2010 ). Bone marrow mesenchymal stem cells (BM-MSCs), a heterogeneous population of plastic-adherent cells, have been successfully used for the treatment of experimental stroke (Li et al, 2002 ).…”

“…In ischemic groups, we observed that the pial microcirculation was progressively reorganized attaining full recovery at 28 days of reperfusion: the capillary density significantly increased, while microvascular permeability and leukocyte adhesion markedly decreased, compared with animals observed at shorter times of reperfusion (Lapi et al, 2013 ).…”

Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

“…Monocyte invasion, and activation of inflammatory pathways, leads to enhanced secretion of growth factors and cytokines that result in positive outward remodeling of the vasculature, forming collaterals [99 ▪▪ ,100,101]. Development of collaterals, increased cerebral blood flow, lengthening of the arteries and outward vascular remodeling have been observed acutely and up to 1 month in animal models after stroke [102–108]. Pharmacological induction of blood pressure and increasing cranial blood flow through vasodilation aimed at increasing pre-existing collateral circulation have shown positive functional outcomes and a reduction in stroke volume [109–112].…”

The compelling arguments for the need of microvascular investigation in COVID-19 critical patients

“…Systemic hypoxia generated by ARDS is one of the main causes that may induce the release of vascular endothelial growth factor (VEGF) [33]. This molecule is related to Hypoxia-Inducible Factor 1, produced under hypoxic conditions [34,35].…”