Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries

Tomita, Minoru; Tsutsumi, Yutaka; Unekawa, Miyuki; Toriumi, Haruki; Suzuki, Noriyuki

doi:10.1016/j.neuroimage.2011.02.078

Cited by 24 publications

(37 citation statements)

References 32 publications

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“…This closure is not likely to be simply a result of the CSD-induced changes in vessel diameter, because it was maximal throughout both the initial dilation and constriction exhibited by the arteries, and because the closure of the paravenous space (i.e., PVS near pial veins) occurred in the absence of any detectable change in the diameter of the pial vein. Based on reports of neuronal (Takano et al, 2007) and astrocytic endfeet (Tomita et al, 2011) swelling after CSD, it may be more likely that the closure of the PVS is secondary to such swelling-especially considering that astrocytic endfeet form the outer wall of the PVS (Jessen et al, 2015). Also, we observed that the PVS around penetrating arteries may close seconds before it closes around the surface arteries, which raises the possibility that the CSD-induced parenchymal swelling spreads from deep layer I up to the pia.…”

Section: Mechanism Of Pvs Closurementioning

confidence: 99%

“…Current knowledge identifies AQP4, a channel that regulates water transport through cell membranes, as a key player in the dynamics of glymphatic flow (Iliff et al, 2012;Nagelhus and Ottersen, 2013). In fact, the presence of AQP4 in astrocytic endfeet makes it an ideal candidate to mediate (1) CSD-induced astrocytic endfeet swelling (Tomita et al, 2011); (2) CSD-induced accumulation of solutes, such as potassium, ATP, and glutamate in the interstitial fluid (Schock et al, 2007;Charles and Brennan, 2009;Ayata and Lauritzen, 2015), potentially due to reduced interstitial flow; and (3) the closure of the PVS. If AQP4 modulation could prevent PVS closure and subsequent flow impairment, then it could be a potential target for migraine treatment.…”

Section: Mechanism Of Slowed Dye Clearancementioning

confidence: 99%

“…Each of these substances has been shown to produce strong activation of nociceptors [glutamate (MacIver and Tanelian, 1993;Du et al, 2001;Cairns et al, 2002); ATP (Cook and McCleskey, 2002;Molliver et al, 2002;Dussor et al, 2008;Zhao and Levy, 2015); potassium (Strassman et al, 1996)]. Immediate onset of headache after aura could be triggered by such chemicals released into the cortical interstitial fluid during CSD, which then enter the PVS around surface pial vessels and activate nociceptors that innervate those vessels (O'Connor and van der Kooy, 1986;Suzuki et al, 1989) or the pial surface itself (Kosaras et al, 2009) in certain areas of the brain. Delayed onset of headache could be caused by the temporary blockade of outflow of excitatory or inflammatory chemicals from the cortex following CSD, which might prevent these chemicals from reaching dural nociceptors until the PVS reopens.…”

Section: Mechanism Of Slowed Dye Clearancementioning

confidence: 99%

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Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

et al. 2017

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Functioning of the glymphatic system, a network of paravascular tunnels through which cortical interstitial solutes are cleared from the brain, has recently been linked to sleep and traumatic brain injury, both of which can affect the progression of migraine. This led us to investigate the connection between migraine and the glymphatic system. Taking advantage of a novel in vivo method we developed using two-photon microscopy to visualize the paravascular space (PVS) in naive uninjected mice, we show that a single wave of cortical spreading depression (CSD), an animal model of migraine aura, induces a rapid and nearly complete closure of the PVS around surface as well as penetrating cortical arteries and veins lasting several minutes, and gradually recovering over 30 min. A temporal mismatch between the constriction or dilation of the blood vessel lumen and the closure of the PVS suggests that this closure is not likely to result from changes in vessel diameter. We also show that CSD impairs glymphatic flow, as indicated by the reduced rate at which intraparenchymally injected dye was cleared from the cortex to the PVS. This is the first observation of a PVS closure in connection with an abnormal cortical event that underlies a neurological disorder. More specifically, the findings demonstrate a link between the glymphatic system and migraine, and suggest a novel mechanism for regulation of glymphatic flow.

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Section: Mechanism Of Pvs Closurementioning

confidence: 99%

Section: Mechanism Of Slowed Dye Clearancementioning

confidence: 99%

Section: Mechanism Of Slowed Dye Clearancementioning

confidence: 99%

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Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

et al. 2017

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“…For example, Vogel et al have reported that a moderate hypocapnia decreased the heterogeneity of capillary perfusion in rat brain [2]. Moreover, Tomita et al have reported a neuro-capillary coupling between neurons and capillary RBC motion, in which the neuronal activation modulated regional capillary blood flow in rat brain [3]. These findings have evidenced the involvement of cerebral capillary flow dynamics with the brain pathophysiology.…”

Section: Introductionmentioning

confidence: 98%

Cerebral capillary velocimetry based on temporal OCT speckle contrast

Choi

Wan

et al. 2016

Biomed. Opt. Express

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Abstract:We propose a new optical coherence tomography (OCT) based method to measure red blood cell (RBC) velocities of single capillaries in the cortex of rodent brain. This OCT capillary velocimetry exploits quantitative laser speckle contrast analysis to estimate speckle decorrelation rate from the measured temporal OCT speckle signals, which is related to microcirculatory flow velocity. We hypothesize that OCT signal due to sub-surface capillary flow can be treated as the speckle signal in the single scattering regime and thus its time scale of speckle fluctuations can be subjected to single scattering laser speckle contrast analysis to derive characteristic decorrelation time. To validate this hypothesis, OCT measurements are conducted on a single capillary flow phantom operating at preset velocities, in which M-mode B-frames are acquired using a high-speed OCT system. Analysis is then performed on the time-varying OCT signals extracted at the capillary flow, exhibiting a typical inverse relationship between the estimated decorrelation time and absolute RBC velocity, which is then used to deduce the capillary velocities. We apply the method to in vivo measurements of mouse brain, demonstrating that the proposed approach provides additional useful information in the quantitative assessment of capillary hemodynamics, complementary to that of OCT angiography.

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“…Addressing this question is complex due to the need to analyze large ensembles of capillaries with sufficient spatiotemporal resolution. 5 Techniques such as confocal microscopy and two photon microscopy (TPM) have been employed to capture individual capillaries in rodent cerebral cortex, [6][7][8] finding that, under stimulation, capillary RBC-flux has a tendency to saturate at a high RBC-flux value. 6 This observation further leads to the question of how the dynamic RBC-flux heterogeneity correlates with brain oxygen delivery.…”

Section: Introductionmentioning

confidence: 99%

Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice

Lee

Boas

et al. 2016

J Cereb Blood Flow Metab

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We employed optical coherence tomography to measure cerebral cortical capillary red blood cell (RBC) flux in mice. The results suggest that baseline-flux weakly depends on cortical depth. Furthermore, under hypercapnia, low baselineflux capillaries exhibit greater flux increases while the higher ones saturate, resulting in RBC-flux homogenization. Powerspectrum analysis indicates that higher flux capillaries saw greater flux variability in the low-frequency range (0.01-0.1 Hz) both at baseline and during hypercapnia. These results suggest that lower baseline-flux capillaries have more reserve to deliver oxygen with increased blood flow; but higher ones more strongly impact the low-frequency fluctuations associated with BOLD fMRI measurements of resting state functional connectivity.

show abstract

Oscillating neuro-capillary coupling during cortical spreading depression as observed by tracking of FITC-labeled RBCs in single capillaries

Cited by 24 publications

References 32 publications

Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

Cerebral capillary velocimetry based on temporal OCT speckle contrast

Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice

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