Title:Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca2+ Sensitivity
Volume: 11
Issue: 5
Author(s): Lawrence D. Longo and Ravi Goyal
Affiliation:
Keywords:
Cerebral vasculature, fetus, newborn, calcium signaling.
Abstract: As compared to the adult, the developing fetus and newborn infant are at much greater risk for dysregulation of
cerebral blood flow (CBF), with complications such as intraventricular and germinal matrix hemorrhage with resultant
neurologic sequelae. To minimize this dysregulation and its consequences presents a major challenge. Although in many
respects the fundamental signal transduction mechanisms that regulate relaxation and contraction pathways, and thus
cerebrovascular tone and CBF in the immature organism are similar to those of the adult, the individual elements, pathways,
and roles differ greatly. Here, we review aspects of these maturational changes of relaxation/contraction mechanisms
in terms of both electro-mechanical and pharmaco-mechanical coupling, their biochemical pathways and signaling
networks. In contrast to the adult cerebrovasculature, in addition to attenuated structure with differences in multiple cytoskeletal
elements, developing cerebrovasculature of fetus and newborn differs in many respects, such as a strikingly increased
sensitivity to [Ca2+]i and requirement for extracellular Ca2+ for contraction. In essence, the immature cerebrovasculature
demonstrates both “hyper-relaxation” and “hypo-contraction”. A challenge is to unravel the manner in which
these mechanisms are integrated, particularly in terms of both Ca2+-dependent and Ca2+-independent pathways to increase
Ca2+ sensitivity. Gaining an appreciation of these significant age-related differences in signal mechanisms also will be
critical to understanding more completely the vulnerability of the developing cerebral vasculature to hypoxia and other
stresses. Of vital importance, a more complete understanding of these mechanisms promises hope for improved strategies
for therapeutic intervention and clinical management of intensive care of the premature newborn.
