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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/24258

Title: Long-term Changes in Alveolarization in the Postnatal Rat Following Transient Inhibition of Early "Classical" Alveologenesis
Authors: Lau, Mandy
Advisor: Tanswell, Keith
Department: Physiology
Keywords: alveolarization
lung development
alveologenesis
secondary crests
septation
imatinib
Issue Date: 6-Apr-2010
Abstract: Rationale: Activation of the platelet-derived growth factor receptors-α and -β (PDGF-Rα and -Rβ) is critical in the formation of secondary crests/septa during alveologenesis, and its regulation has been found to be disrupted in rat lung injury models. Objective: To determine whether the process of secondary septation can occur after transient pharmacologic inhibition of PDGF-R action during postnatal days (P)1 – 7 in rats. Hypothesis: The initial process of secondary crest formation is time-limited and, if missed, will result in a permanent loss of alveoli. Methods: Imatinib mesylate, a PDGF-R inhibitor, was injected intraperitoneally from P1 – 7. Pups were sacrificed on P2, 4, 8, 14, 28 and 65 for studies of alveolar development. Main results: The injection of imatinib inhibited PDGF-R action, resulting in a permanent decrease in alveolar number in treated rats. Conclusions: Inhibition of secondary septation during the first 7 days of life resulted in a decrease in alveolar number lasting into early adult life. This is consistent with a critical time window for secondary septation, which, if disrupted, results in long-term adverse effects on lung development.
URI: http://hdl.handle.net/1807/24258
Appears in Collections:Master
Department of Physiology - Master theses

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