Oxygen modulation of neurovascular coupling in the retina

Abstract

Neurovascular coupling is a process through which neuronal activity leads to local increases in blood flow in the central nervous system. In brain slices, 100% O 2 has been shown to alter neurovascular coupling, suppressing activity-dependent vasodilation. However, in vivo, hyperoxia reportedly has no effect on blood flow. Resolving these conflicting findings is important, given that hyperoxia is often used in the clinic in the treatment of both adults and neonates, and a reduction in neurovascular coupling could deprive active neurons of adequate nutrients. Here we address this issue by examining neurovascular coupling in both ex vivo and in vivo rat retina preparations. In the ex vivo retina, 100% O 2 reduced light-evoked arteriole vasodilations by 3.9-fold and increased vasoconstrictions by 2.6-fold. In vivo, however, hyperoxia had no effect on light-evoked arteriole dilations or blood velocity. Oxygen electrode measurements showed that 100% O 2 raised pO 2 in the ex vivo retina from 34 to 548 mm Hg, whereas hyperoxia has been reported to increase retinal pO 2 in vivo to only ∼53 mm Hg [Yu DY, Cringle SJ, Alder VA, Su EN (1994) Am J Physiol 267:H2498-H2507]. Replicating the hyperoxic in vivo pO 2 of 53 mm Hg in the ex vivo retina did not alter vasomotor responses, indicating that although O 2 can modulate neurovascular coupling when raised sufficiently high, the hyperoxia-induced rise in retinal pO 2 in vivo is not sufficient to produce a modulatory effect. Our findings demonstrate that hyperoxia does not alter neurovascular coupling in vivo, ensuring that active neurons receive an adequate supply of nutrients.functional hyperemia | glial cells | prostaglandins N euronal activity in the CNS induces local increases in blood flow (1, 2), a homeostatic response termed functional hyperemia. Neurovascular coupling, the process mediating this response, is thought to involve signaling from neurons to glial cells to blood vessels. Neuronal activity induces a rise in intracellular Ca 2+ in glial cell endfeet surrounding vessels, leading to the release of vasoactive arachidonic acid metabolites and resulting in vasomotor responses (2-6). Experiments in brain slices and in the ex vivo retina have revealed that glial activation can evoke both vasodilation and vasoconstriction. Evoked vasodilations are mediated by cyclooxygenase (COX) products (3, 5) and epoxyeicosatrienoic acids (EETs) (6-9), whereas vasoconstrictions are mediated by 20-hydroxyeicosatetraenoic acid (20-HETE) (4,6).A recent study demonstrated that neurovascular coupling is modulated by O 2 in brain slices (10). Both neuronal and glial cell stimulation elicited vasodilations in brain slices exposed to 20% O 2 . In contrast, vasoconstrictions were evoked in the presence of 100% O 2 . However, another recent study reported the opposite effect of O 2 in vivo (11). In that study, increasing systemic O 2 using hyperbaric hyperoxygenation had no effect on cortical functional hyperemia. Resolving these conflicting findings is critical, given that hyperoxia (breat...

Single-cell label-free photoacoustic flowoxigraphy in vivo

“…The study of neurovascular coupling has gained broad interest because hemodynamics may be used as an important surrogate in exploring neuroscience and studying brain disorders (20)(21)(22)(23). Here, we demonstrate that single-RBC FOG can image coupling between visual neural activity and single-RBC oxygen release in the brain.…”

Inversion of neurovascular coupling by subarachnoid blood depends on large-conductance Ca 2+ -activated K + (BK) channels

“…Previous work also has demonstrated that 20-HETE can inhibit BK channels in renal and pial artery smooth muscle cells (29), and increased 20-HETE synthesis has been implicated in vascular pathologies associated with SAH (30). To examine the involvement of 20-HETE in EFS-induced vasoconstriction after SAH, we exposed brain slices to the CYP4a inhibitor, N-hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine (HET0016, 100 nM) (31,32), before EFS. In brain slices from SAH animals, HET0016 did not change the magnitude or time course of EFS-induced elevations in endfoot Ca 2+ or vasoconstriction (Fig.…”

Multiparametric optical coherence tomography imaging of the inner retinal hemodynamic response to visual stimulation

“…Comparable stimulus protocols and experimental designs are frequently used in the literature to study functional hyperemia in the rat retina. 4,11,12 Uniform illumination of the retina was confirmed by imaging the retina onto a CCD camera connected to PC2. Repeated OCT volumes for angiography (128 ylocations × 256 axial scans per frame × 2 frames per y-location) or Doppler OCT (96 y-locations × 1024 axial scans per frame × 1 frame per y-location) were acquired during runs of 10 stimuli separated by 25 s. In one run, a stimulus frequency of 12 Hz was used, while in the other run, stimulus frequencies between 6 and 18 Hz were generated in a random order to test for frequency dependence of the response.…”