Cerebrovascular Dynamics of Autoregulation and Hypoperfusion

Zaharchuk, Greg; Mandeville, Joseph B.; Bogdanov, Alexei A.; Weissleder, Ralph; Rosen, Bruce R.; Marota, John J. A.

doi:10.1161/01.str.30.10.2197

Cited by 118 publications

(21 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected no significant confounding effect of genotype on anaesthesia during fMRI as assessed by the magnitude of mean arterial blood pressure, a sensitive indicator of anaesthesia depth in rodents 43 ( P =0.17). GBR administration produced a short-lived (~8 min) blood pressure decrease (−6.0±6.3 mm Hg and −22.50±5.1 mm Hg in BTBR and B6, respectively) that was, however, well within the autoregulation window under halothane anaesthesia 44,45 and temporally uncorrelated with the fMRI responses (the latter lasting >25 min), thus arguing against a peripheral origin of the discrepant fMRI responses mapped in the two strains.…”

Section: Resultsmentioning

confidence: 92%

Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

et al. 2014

View full text Add to dashboard Cite

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T+ Itpr3tf/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations.

show abstract

Section: Resultsmentioning

confidence: 92%

Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

et al. 2014

View full text Add to dashboard Cite

show abstract

“…It has been shown that hemodynamic regulation is heterogeneous and that functionally induced microvascular changes can occur at small spatial scales, i.e., at the level of columns and layers (Chaigneau et al, 2003; Erinjeri and Woolsey, 2002). Laminar differences in blood volume and flow have been observed in baseline conditions as well as after stimulation, showing that blood flow regulation differs between layers and between superficial vessels and parenchyma (Choi et al, 2010; Moskalenko et al, 1998; Zaharchuk et al, 1999). Baseline blood flow and vascularization are highest in the center of the cortex (Duvernoy et al, 1981; Gerrits et al, 2000; Moskalenko et al, 1998; Weber et al, 2008).…”

Section: Discussionmentioning

confidence: 98%

High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses

Goense

Merkle

Logothetis

2012

Neuron

241

232

View full text Add to dashboard Cite

SUMMARY The six cortical layers have distinct anatomical and physiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, as well as laminar differences in neurovascular coupling.

show abstract

“…18 CBF were measured in WT mice in the following order: baseline (20 minutes), inhaled nitric oxide (40 ppm, 10 minutes), baseline (20 minutes), inhaled carbon dioxide (CO 2 , 10 minutes), and baseline (10 minutes). We used carbon dioxide (CO 2 7%, oxygen 21%, and balance nitrogen) as a positive control since carbon dioxide is known to increase CBF based on a previous report.…”

Section: Methodsmentioning

confidence: 99%

Beneficial Effects of Nitric Oxide on Outcomes after Cardiac Arrest and Cardiopulmonary Resuscitation in Hypothermia-treated Mice

Kida

Shirozu

et al. 2014

Anesthesiology

Self Cite

View full text Add to dashboard Cite

Background Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and reperfusion, role of nitric oxide during TH after CPR remains unclear. Here, we examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. We also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH. Methods Wild-type (WT) mice and mice deficient for nitric oxide synthase 3 (NOS3−/−) were subjected to CA at 37°C and then resuscitated with chest compression. Body temperature was maintained at 37°C (normothermia) or reduced to 33°C (TH) for 24 hours after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in WT mice after CA/CPR. Results Hypothermia up-regulated the NOS3-dependent signaling in the brain (n=6–7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n=5–6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3−/− mice (n=6) after CA/CPR compared to NOS3−/− mice that were treated with hypothermia alone (n=6, P<0.05). Breathing nitric oxide at 40 (n=9) or 60 (n=9) ppm markedly improved survival rates in TH-treated WT mice (n=51) (both P<0.05 vs TH-treated WT mice). Inhaled nitric oxide during TH (n=7) prevented brain injury compared to TH alone (n=7) without affecting cerebral blood flow after CA/CPR (n=6). Conclusions NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production.

show abstract

Cerebrovascular Dynamics of Autoregulation and Hypoperfusion

Cited by 118 publications

References 68 publications

Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

Dysfunctional dopaminergic neurotransmission in asocial BTBR mice

High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses

Beneficial Effects of Nitric Oxide on Outcomes after Cardiac Arrest and Cardiopulmonary Resuscitation in Hypothermia-treated Mice

Contact Info

Product

Resources

About