Bi-directional communication at the neurovascular unit: implications for neuronal function

Published on October 31, 2016   37 min

Other Talks in the Series: Physiology and Pathophysiology of Neuroglia

0:00
Hello. My name is Jessica Filosa. I'm in the Department of Physiology at Augusta University. As part of this lecture series, the subject of my talk is Bi-directional Communication at the Neurovascular Unit: Implications for Neuronal Function.
0:15
The outline for this lecture is as follow. First, I will briefly discuss the anatomical organization of the cerebral blood vessels and corresponding innervations. Second, I will discuss neurovascular coupling mechanism with an emphasis on potassium signaling. Third, I will introduce a novel in vitro approach to study neurovascular coupling in the brain. And lastly, I will talk about bi-directional communication at the neurovascular unit and provide evidence for vascular to glia to neuronal coupling.
0:47
Even though the brain constitutes a small portion of our total body mass, about 2%, it consumes a significant amount of oxygen and glucose, about 25%. Main reason for this large energy consumption is the need to restore ion influxes which are altered during increases in synaptic activity. Importantly, as the brain is not efficient at storing energy, a continuous supply of oxygen and glucose is needed for normal brain function. This is chiefly accomplished through two fundamental mechanisms. Functional hyperemia or neurovascular coupling, where a local increase in neuronal activity is matched with an increase in cerebral blood flow supply and cerebral autoregulation, which basically maintains constant profusion in the phase of blood pressure changes.
1:39
Before we discuss the mechanisms of neurovascular coupling in the brain, I would like to remind you of the structural arrangement of the cerebral circulation. The vascular tree of the brain originates from large arteries at the base of the brain at the circle of Willis. These large arteries branch into small pial arterioles at the surface of the brain in the subarachnoid space. These vessels constitute the extracerebral circulation.
2:08
As with the subdivisions of the cerebrovascular beds, the innervations of these vessels can be divided into two subgroups, extrinsic and intrinsic innervations. The pial vessels are innervated by peripheral nerves which originate from autonomic and sensory ganglia, and these include sympathetic innervations arising primarily from the superior cervical ganglia, parasympathetic innervations arising from the sphenopalatine and otic ganglia, and sensory innervations arising from the trigeminal ganglia. As these arteries penetrate the brain parenchyma and are past the Virchow-Robin space, they lose the extrinsic innervation.
2:49
We now move on to the innervations of the intracerebral arterioles. And the best studies have been those in the cortex. As the pial arterioles branch off, these branches dive into the brain parenchyma where they continue to branch, leading to an extensive capillary network. As I mentioned in the prior slide and as shown here in this diagram, when the vessels are past the Virchow-Robin space, they lose their extrinsic innervation and are now under the control of signals released from neurons and astrocytes from within the brain, thus the name for intrinsic innervation. Also, as shown in the diagram, while a few perivascular neuronal varicosities directly contact the basal lamina of the blood vessels, the majority are viewed on astrocytic endfeet processes, which encase or wrap around the abluminal surface of these intracerebral arterioles. In this table, you can see the various signals released by neurons and/or astrocytes which lead to either dilation or constriction of these vessels.
3:50
As shown in this slide, the intimate anatomical and neurophysiological association between neurons, astrocytes, and blood vessels have led to the term neurovascular unit. A major focus of our work is to understand the mechanisms by which increases in neuronal activity are transduced into a vascular response. It has been now well-accepted that in addition to neuronal signals having a direct effect on blood vessels such as nitric oxide, neuronal activation leads to the activation of astrocytes, which in turn release the signals at the gliovascular interface contributing to the regulation of vascular tone. In the remaining of this talk, I will focus on the role of astrocytes in neurovascular coupling.
4:34
So how do astrocytes contribute to the regulation of vascular tone? Over the past several years, several groups demonstrated that astrocytic activation can induce dilation or constriction or both of parenchymal arterioles. In fact, in this table, you can see a few of the signals by which astrocytes can modulate vascular tone. The duality of the vascular response, meaning, dilation or constriction has been a major controversy in the field, mainly because it has been difficult to understand the physiological meaning for a vasoconstriction at the site of an increased neuronal activity where increases in cerebral blood flow are needed. A few groups have attempted to explain the mechanism underlying dilations and constrictions mediated by astrocytes. In an elegant study from Gordon from MacVicar's group, they suggested that one possibility is due to brain metabolism. They showed that at low oxygen conditions, astrocytic activation resulted in dilations, and at high oxygen conditions, astrocytic activation gave rise to a vasoconstriction. The author suggested that the mechanism leading to these dual vascular responses is glycolysis. As in low oxygen condition, it will result in higher lactate levels, and lactate inhibits prostaglandin transporters, thus increasing PGE2 and favoring vasodilation. And as discussed in their 2004 paper, at higher oxygen levels, arachidonic acid metabolism will favor 20-HETE formation and thus vasoconstriction. In another excellent study, Girouard from Nelson's group showed that changes in the extracellular potassium concentration via activation of large-conductance, calcium-activated potassium channels, I will refer to these as BK channels, can mediate dilations or constriction. These studies were conducted at high oxygen conditions. And thus, it is clear that there are several mechanisms and conditions by which astrocytes can induce both dilation and constriction of parenchymal arterioles.
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Bi-directional communication at the neurovascular unit: implications for neuronal function

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