Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca²⁺ Sensitivity

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.

Cite this article as:

Longo D. Lawrence and Goyal Ravi, Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca²⁺ Sensitivity, Current Vascular Pharmacology 2013; 11 (5) . https://dx.doi.org/10.2174/1570161111311050008