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Syn3 and D-Syn3 attenuate brain infarct volume loss after hypoxic-ischemic brain injury in neonatal rats

Description

Abstract:
Perinatal brain injury (PBI) results from the severe lack of oxygen in the uterus. This can result in brain dysfunction, including hypoxic-ischemic encephalopathy (HIE). PBI affects more than 10,000 infants each year in the United States. Moreover, neonatal HIE brain injury is the leading cause of infant mortality and long-term neurologic disability (e.g., cerebral palsy). Hypothermia, the only approved treatment for HIE, reduces long- and short-term complications from brain trauma or low oxygen. However, this therapy is limited to only treating full-term infants. In this thesis, I investigate how the developing brain responds to hypoxic ischemia (HI) and examine the efficacy of two newly defined neuroprotective and immunomodulatory peptidomimetic drugs, Syn3 and D-Syn3, to attenuate HIE-related brain damage in the neonate. Postnatal day 7 rats were assigned to 4 groups: Placebo (HI-PL n=11), Sham (n=8), HI-Syn3 (n=16), and HI-DSyn3 (n=16). Animals underwent unilateral ligation of the carotid artery followed by administration of 8% oxygen and balanced nitrogen for 90 minutes. 1 mg/kg of Syn3 or D-Syn3 was injected intraperitonially (I.P.) into the rats in group HI-Syn3 or HI-DSyn3 immediately (0-hr abruption), 24-, and 48-hr after hypoxic-ischemic brain injury. Brains were removed, cryo-sectioned, and stained with cresyl violet and analyzed in ImageJ (NIH) to determine infarct volume. Significantly, the infarct volume after HI-brain injury was attenuated (Kruskal-Wallis and Dunn’s test, female+males: Syn3, p=0.0224; D-Syn3, p=0.0067) following treatment with 1 mg/kg b.w. Syn3 or D-Syn3 in male and female neonatal rats.
Notes:
Thesis (Sc. M.)--Brown University, 2024

Citation

Muñoz, Christian Alexander, "Syn3 and D-Syn3 attenuate brain infarct volume loss after hypoxic-ischemic brain injury in neonatal rats" (2024). Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:68xexwc6/

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