title: Neonatal lung and airway injury: a role for neurotrophins.
abstract: Maintenance of patency in distal airways is essential for gas exchange in neonatal life, and its disruption may have long-lasting effects on respiratory function. However, neural mechanisms that regulate caliber of intrapulmonary airways during early postnatal life, and their disruption by hyperoxic exposure, have not been well characterized. We have previously shown that cholinergically mediated airway contractile responses in rat pups are upregulated after hyperoxic exposure, and that increased expression of neuropeptides, such as substance P, may be contributory. More recently, we have documented impairment of neurally mediated airway relaxation in response to hyperoxic stress associated with loss of nitric oxide and prostaglandin-induced airway relaxation as well as inhibition of long chain myosin phosphatase. Our most recent data demonstrate significantly enhanced expression of the neurotrophin, brain-derived neurotrophic factor (BDNF) and its high affinity specific tyrosine kinase B (TrkB) receptor in hyperoxia-exposed airway smooth muscle. The existence of a BDNF-TrkB receptor autocrine and paracrine loops in the airways provides a basis for understanding local regulatory mechanisms of airway homeostasis. A mechanistic role for BDNF-TrkB signaling in hyperoxia-induced airway hyperreactivity in early postnatal life could serve to modulate both afferent and efferent neural pathways that result in enhanced contractile responses of immature airways exposed to hyperoxic stress. Greater insight into these neural pathways may lead to future preventive strategies for preterm infants surviving neonatal intensive care and developing chronic lung disease.
authors.affiliation: Department of Pediatrics, Case Western Reserve University School of Medicine, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yao
authors.forename: Syed I
authors.initials: SI
authors.lastname: Zaidi
authors.forename: Musa A
authors.initials: MA
authors.lastname: Haxhiu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019898:Autocrine Communication; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D003422:Critical Care; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008168:Lung / Q000294:innervation / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D009414:Nerve Growth Factors / Q000378:metabolism; D019899:Paracrine Communication; D051381:Rats
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors