Astrocytes and the regulation of cerebral blood flow

Koehler, Raymond C.; Roman, Richard J.; Harder, David R.

doi:10.1016/j.tins.2008.11.005

Cited by 389 publications

(319 citation statements)

References 106 publications

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“…It has been proposed that astrocytes may contribute primarily to the maintenance of hemodynamic response rather than its initiation. 17 Our results comparing 4-and 20-second stimulation protocols ( Figures 2E and 2F) show that the kinetic of the BOLD signals are virtually identical at the initiation phase and maintenance, in WT and IP 3 R2 KO mice. Overall, these results discard an IP 3 R2-mediated contribution of astrocytes to the fMRI signal generation or the evoked neurotransmission.…”

Section: Resultsmentioning

confidence: 63%

Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes

Jégo

Pacheco-Torres

Araque

et al. 2014

J Cereb Blood Flow Metab

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Functional magnetic resonance imaging (fMRI) is a fundamental tool to investigate human brain networks. However, the cellular mechanisms underlying fMRI signals are not fully understood. One hypothetical mechanism is the putative vascular control exerted by cytosolic calcium in perivascular astrocytes. We have performed combined fMRI-electrophysiology experiments in mice lacking the inositol 1,4,5-triphosphate-type-2 receptor, with the primary pathway of cytosolic calcium increase eliminated into astrocytes. Our results show that evoked electrophysiologic activity and fMRI signals acquired during either transient or sustained neuronal activations occur independently of these large calcium signals. This result challenges the suggested intermediary role of astrocytic calcium surges in fMRI-signal generation.

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Section: Resultsmentioning

confidence: 63%

Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes

Jégo

Pacheco-Torres

Araque

et al. 2014

J Cereb Blood Flow Metab

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“…The importance of astrocytes in the regulation of cerebral blood flow regulation cannot be overlooked. [11][12][13][14][15] Cortical glia limitans astrocytes at the brain surface are critical for selected dilator responses of pial arterioles, in particular, to ADP. 14,15 In many cases, vasodilator stimuli require contribution of both endothelial and astrocyte components of the neurovascular unit.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] Astrocytes are key cell components of the cerebral blood flow regulation. [11][12][13][14][15] However, until now, the functional consequences of neonatal seizures on the astrocyte component of the neurovascular unit remain unknown. We also wanted to investigate whether the therapeutically preferable enteral route of CORM-A1 administration can deliver gaseous CO to the brain to provide long-term cerebrovascular protection.…”

Section: Introductionmentioning

confidence: 99%

Enteral Supplements of a Carbon Monoxide Donor CORM-A1 Protect against Cerebrovascular Dysfunction Caused by Neonatal Seizures

Liu

Fedinec

Leffler

et al. 2014

J Cereb Blood Flow Metab

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Cerebral blood flow dysregulation caused by oxidative stress contributes to adverse neurologic outcome of seizures. A carbon monoxide (CO) donor CORM-A1 has antioxidant and cytoprotective properties. We investigated whether enteral supplements of CORM-A1 can improve cerebrovascular outcome of bicuculline-induced seizures in newborn piglets. CORM-A1 (2 mg/kg) was given to piglets via an oral gastric tube 10 minutes before or 20 minutes after seizure onset. Enteral CORM-A1 elevated CO in periarachnoid cerebrospinal fluid and produced a dilation of pial arterioles. Postictal cerebral vascular responses to endothelium-, astrocyte-, and vascular smooth muscle-dependent vasodilators were tested 48 hours after seizures by intravital microscopy. The postictal responses of pial arterioles to bradykinin, glutamate, the AMPA receptor agonist quisqualic acid, ADP, and heme were greatly reduced, suggesting that seizures cause injury to endothelial and astrocyte components of the neurovascular unit. In contrast, in the two groups of piglets receiving enteral CORM-A1, the postictal cerebral vascular responsiveness to these dilators was improved. Overall, enteral supplements of CORM-A1 before or during seizures offer a novel effective therapeutic option to deliver cytoprotective mediator CO to the brain, reduce injury to endothelial and astrocyte components of cerebral blood flow regulation and to improve the cerebrovascular outcome of neonatal seizures.

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“…As depicted in Fig. 9H, these astrocytes might have been the components of neurovascular unit responsible for controlling cerebral blood flow and maintaining the integrity of blood-brain barrier (Koehler et al, 2009). …”

Section: Midbrain Astroglia Responsesmentioning

confidence: 99%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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Astrocytes and the regulation of cerebral blood flow

Cited by 389 publications

References 106 publications

Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes

Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes

Enteral Supplements of a Carbon Monoxide Donor CORM-A1 Protect against Cerebrovascular Dysfunction Caused by Neonatal Seizures

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

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Astrocytes and the regulation of cerebral blood flow

Cited by 389 publications

References 106 publications

Functional MRI in Mice Lacking IP3-Dependent Calcium Signaling in Astrocytes

Functional MRI in Mice Lacking IP3-Dependent Calcium Signaling in Astrocytes

Enteral Supplements of a Carbon Monoxide Donor CORM-A1 Protect against Cerebrovascular Dysfunction Caused by Neonatal Seizures

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

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Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes

Functional MRI in Mice Lacking IP₃-Dependent Calcium Signaling in Astrocytes