Big brain, small body: towards a better understanding of cerebrovascular physiology in children

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Abstract

The human brain has exquisite sensitivity to changes in the pressure of arterial carbon dioxide () whereby cerebral blood flow (CBF) increases with hypercapnia and decreases with hypocapnia. This response, termed cerebrovascular reactivity (CVR), is a vasomotor mechanism whereby CBF is modulated through constriction and dilatation throughout the cerebrovascular tree, from the large extracranial and intracranial conduit arteries and middle cerebral arteries to the arterioles in the pia mater. The pial vessels are the principal site of cerebrovascular resistance modulation, both because of their large collective surface area but also because their tone is coupled to the metabolic state of downstream neurovascular units (Willie et al. 2014). The concept of CVR as normally defined is related to, but not the same as, cerebrovascular reserve capacity; this reserve refers to the amount cerebral perfusion can increase from baseline in response to a stimulus (Willie et al. 2014). Impaired, or exhausted, CVR is a hallmark of steno-occlusive cerebrovascular diseases. The assessment of CVR can be probed using various vasoactive stimuli in combination with flow/velocity sensitive measurement techniques such as transcranial Doppler ultrasonography (TCD) as well as PET and SPECT imaging. In some respects, these modalities are not always optimal; PET/SPECT images are of low spatial resolution and image acquisition relies on the intravenous injection of radionuclides, while TCD cannot provide localized CVR information and provides only information on perfusion at the level of the middle cerebral artery. The use of blood oxygenation dependent (BOLD) MRI provides an alternative method to measure CVR, an approach that is gaining interest as a non-invasive way to diagnose and localize impairment, and track longitudinal changes in CVR. The regulation of CBF in adults is relatively well studied and appreciated. In contrast, the influence of maturation, which is reflected in critical surges in neural development, myelination, metabolic demands and increased cerebral utilization of glucose is poorly understood in the paediatric brain. Remarkably, global CBF at birth is, on average, 50 ml (100 g)−1 min−1, increasing after birth to a maximum of 70–80 ml (100 g)−1 min−1 at 5–7 years and then decreasing to reach adult levels after 19 years (Takahashi et al. 1999). The global CBF represents more than 50% of cardiac output at the peak value around 1–3 years of age, indicating why this age group is at risk for cerebrovascular catastrophes consequent to perioperative systemic disorders. This dynamic pattern of change probably represents the consequence of brain development and subsequent ‘shaping’ of neurons, synapses and pathways that occurs with maturation. Despite the documentation on CBF during developmental changes, data on CVR are lacking and the focus of a new study in this issue of The Journal of Physiology by Leung and co-workers (Leung et al. 2016). Here, the authors utilized arterial spin labelling imaging and BOLD MRI to characterize the developmental trajectories of CBF and CVR in grey (GM) and white matter (WM) in healthy children and young adults (Leung et al. 2016). The novel findings revealed that, somewhat dissimilar to the trajectory of CBF, CVR in GM and WM increases in children aged 9–15 years and decreases thereafter. In contrast, the mean CBF in GM and WM declines approximately 50% from participants aged 9–30 years. The new CBF and CVR data from Leung and co-workers are important as they provide key data in healthy children that can be used for preliminary comparisons against various pathologies. The findings also provide an impetus for future research on topics such as how pubertal development affects CVR development in girls and boys, and the longitudinal tracking of CVR changes in both healthy children and those with pathology to confirm developmental trajectories by age, maturation and sex and how disease alters these trajectories. Interpretation of BOLD-CVR maps also remains subjective and a method to standardize CVR-related properties for healthy and diseased tissue has been developed only recently (Sobczyk et al. 2014). These approaches, along with more readily accessible non-invasive methods (e.g. TCD), should now be applied and explored in children. Examining key mechanism(s) of CBF regulation and brain development in healthy children is important not only for improving understanding of the progress of brain maturation but may also facilitate early diagnosis and evaluation of various developmental disorders. None declared.

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