Measurement of Neurovascular Coupling in Neonates

Abstract

Neurovascular coupling refers to the mechanism that links the transient neural activity to the subsequent change in cerebral blood flow, which is regulated by both chemical signals and mechanical effects. Recent studies suggest that neurovascular coupling in neonates and preterm born infants is different compared to adults. The hemodynamic response after a stimulus is later and less pronounced and the stimulus might even result in a negative (hypoxic) signal. In addition, studies both in animals and neonates confirm the presence of a short hypoxic period after a stimulus in preterm infants. In clinical practice, different methodologies exist to study neurovascular coupling. The combination of functional magnetic resonance imaging or functional near-infrared spectroscopy (brain hemodynamics) with EEG (brain function) is most commonly used in neonates. Especially near-infrared spectroscopy is of interest, since it is a non-invasive method that can be integrated easily in clinical care and is able to provide results concerning longer periods of time. Therefore, near-infrared spectroscopy can be used to develop a continuous non-invasive measurement system, that could be used to study neonates in different clinical settings, or neonates with different pathologies. The main challenge for the development of a continuous marker for neurovascular coupling is how the coupling between the signals can be described. In practice, a wide range of signal interaction measures exist. Moreover, biomedical signals often operate on different time scales. In a more general setting, other variables also have to be taken into account, such as oxygen saturation, carbon dioxide and blood pressure in order to describe neurovascular coupling in a concise manner. Recently, new mathematical techniques were developed to give an answer to these questions. This review discusses these recent developments.

Small Vessel Disease-Related Dementia: An Invalid Neurovascular Coupling?

“…RhoA/ROCK counteracts this through MLCP inactivation and calcium desensitization [217,220]. ROCK/Rho decreases eNOS expression and affects the availability of NO [221]; it has also been proven in brain small vessels, even if these effects have been largely studied in major vessel disease (coronary) [82]. Three potentially functional eNOS polymorphisms (T-786C, intron 4ab, G894T) located toward the 5 flanking end of the gene are known to be considered as being present in SVD and also in isolated lacunar infarction and ischemic leukoaraiosis [222].…”

“…The perivascular compartment contains several cell types, like perivascular macrophages, pial cells, mast cells, nerve fibers, and collagen fibers [80]. Usually, as arterioles penetrate deeper into the brain, the glial membrane, the pericyte membrane fuse together and then obliterate the perivascular spaces [80,81], but it has been proposed that either in humans either in animals, the perivascular space could act as a brain lymphatic system, also being defined as "para-arteriolar", "para-venular", "paravascular", or "glymphatic" [82]. This system has many complex functions (further in the review, we will explain it regarding neurovascular coupling), but it seems likely to exert the drainage work of the brain.…”

“…Therefore, modification of this system produces deleterious effects, whose results are an accumulation of catabolites and toxic substances, together with a pronounced neural starvation [83,84]. In SVD, this system is invalid; one of the SVD hallmarks is the enlargement and widening of PVS, due to an obstructive process that is maintained by catabolites, proteins, and cell debris [82]. In small vessel disease, the occlusion of deep periventricular-draining veins is also evident [43], together with the disruption of the blood-brain barrier (BBB).…”

“…The immobility of the fluid drainage can support PVS's role in different diseases: the possible explanation of the PVS involvement in SVD, is the argued relationship demonstrated between an altered cerebrovascular reactivity (CVR), which is the change in cerebral blood flow in response to a vaso-active stimulus in the so-called neurovascular coupling, the found BBB dysfunction, and the correspondent perivascular inflammation [86]. Therefore, a lacuna should not indicate an enlarged perivascular space, as it is, still nowdays; it should never be the correspondent of the CSF-filled cavities on brain MRI or residual lesion of a small hemorrhage [82,[87][88][89][90][91][92]. Nowadays, it should be more appropriate for the definition "lacuna of presumed vascular origin" to replace the term "lacuna" [20,[93][94][95][96].…”

Transcranial Doppler combined with quantitative electroencephalography brain function monitoring for estimating the prognosis of patients with posterior circulation cerebral infarction

“…After the onset of ischemic stroke, CBF is disrupted throughout the affected region of the brain; this sharp reduction in blood ow results in de cient adenosine triphosphate levels and subsequent ionic disruption and metabolic failure, which progresses within minutes to neuronal necrosis [6]. The close temporo-spatial relationship between neural activity and regional CBF is known as neurovascular coupling [7,8].…”