ReviewCerebral microvascular pericytes and neurogliovascular signaling in health and disease
Section snippets
Cerebral circulation
The brain surface is covered by a network of pial arteries and veins (Duvernoy et al., 1981). Arteries branching off the pial network dive in the brain, while intracortical veins surface and join to pial veins (Duvernoy et al., 1981, Lauwers et al., 2008) (Fig. 1). The honeycomb-like structure of pial arterial/arteriolar network allows redistribution of blood during activation of cortical columns to match the increased focal demand of the activated brain area via penetrating arteries (Blinder
Neurovascular unit and neurovascular coupling
The neurovascular unit (NVU), which is composed of the endothelia, pericytes, neurons and astrocyte end-feet, plays an integrating role in matching the metabolic demand with the blood flow in addition to the vasodilation induced by adenosine and lactate produced as end-products of the metabolic activity and by NO of endothelial origin (Fig. 3) (Abbott et al., 2006, Attwell et al., 2010, Iadecola, 2004, Ko et al., 1990, Li and Iadecola, 1994). Recent studies suggest that astrocytes play an
Pericytes
Pericytes are uniquely positioned within the NVU; they communicate with other cells of the NVU and regulate several microcirculatory functions such as maintenance of the blood–brain barrier (BBB) and basal lamina, regulation of the angiogenesis, immune responses and scar formation in addition to their role in control of the microvascular flow (Attwell et al., 2010, Göritz et al., 2011, Hamilton et al., 2010, Krueger and Bechmann, 2010, Thomas, 1999) (Fig. 4). They may also function as
Microvascular injury after recanalization therapies for stroke
Thrombolysis trials have unambiguously demonstrated the presence of a salvageable brain tissue after ischemic stroke (Donnan et al., 2011, Heiss, 2011). However, a short therapeutic time window limits the use of recanalization therapies for majority of stroke patients (Donnan et al., 2009, Lees et al., 2010). This brief therapeutic window is attributed to rapid loss of neuronal viability in the ischemic penumbra supported by collaterals (Del Zoppo et al., 2011, Donnan et al., 2011). However,
Incomplete microcirculatory reflow after recanalization
An impaired tissue reperfusion due to loss of microvascular patency (no-reflow phenomenon) was first noted after global and focal cerebral ischemia more than 50 years ago (Ames et al., 1968, Crowell and Olsson, 1972). Starting one hour after MCA occlusion, some of the capillaries show constrictions whereas pre-capillary arterioles generally remain open (Belayev et al., 2002, Little et al., 1976). Narrowed capillary lumina are filled with entrapped erythrocytes, leukocytes and fibrin-platelet
Pericyte dysfunction causes diabetic retinopathy
Diabetic retinopathy is characterized by occlusion of retinal microvessels, acellular capillaries, microaneurysms, breakdown of the blood–retinal barrier, hemorrhages, macular edema and angiogenesis (Willard and Herman, 2012). Pericyte loss in the retinal microvessels is a hallmark of diabetic retinopathy. Platelet-derived growth factor β (PDGFβ) knockout mice provided the first insight to the role of pericytes in diabetic retinopathy because their microvessels were devoid of pericytes and
Microvascular dysfunction as a cause of neurodegenerative diseases
Dementia had been attributed to age-related changes in major cerebral arteries until the second half of 20th century when the interest shifted to deficiency in cholinergic innervation of the hippocampus and neocortex as well as to cerebral amyloid metabolism. However, the vascular hypothesis has recently been reawakened but, this time, based on the discoveries at microcirculatory level (Brown and Thore, 2011, De la Torre and Mussivand, 1993, Iadecola, 2010, Iadecola, 2004, Stanimirovic and
Conclusion
Introduction of the NVU concept has shifted the focus of research on neurovascular coupling and cerebral vascular diseases from neuron-centric views to the complex communication between elements of the NVU. With this new perspective, we now better appreciate how the activity-flow coupling in CNS works and that a successful neuroprotection is not feasible without microvascular protection. The ischemia/reperfusion-induced NVU injury, incomplete recirculation after recanalization and the role of
Acknowledgments
Dr. Turgay Dalkara׳s research is supported by The Turkish Academy of Sciences. Dr. Luis Alarcon-Martinez׳s research is supported by the Co-funded Brain Circulation Scheme of Marie Curie Actions into the 7th Framework Program of European Union. Dr. Luis Alarcon-Martinez prepared Fig. 3, Fig. 5.
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