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Type of Resource (primo): dissertations
Name: Personal
Name: Personal
Name: Personal
Name: Personal
Name: Personal
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Note: thesis: Thesis (Sc. M.)--Brown University, 2023
Genre (aat): theses
Abstract: Hypoxic-ischemic encephalopathy (HIE) is a type of neuronal dysfunction which occurs when the brain has limited oxygen or blood flow. Brain injuries caused by HIE could lead to neuronal tissue impaired and long-term cognitive deficits. Currently, the only approved treatment for HIE is therapeutic hypothermia, which has a narrow therapeutic window with limited effectiveness. It was only approved to be used as the treatment for full-term infants since it is not considered as a safe tool for treatment in preterm neonates. The need of a novel neuroprotective agent as the adjunct or alternative treatment of therapeutic hypothermia is urgent to improve the outcomes of the treatment with increased restoration and protection abilities. Previous studies from our lab have shown human plasma-derived Inter-alpha-Inhibitor Protein (hIAIP) has neuroprotective effects and behavioral benefits in a sex-dependent manner. The effect of hIAIP as an adjunct treatment working with therapeutic hypothermia remains to be determined. In this study, righting reflex, negative geotaxis, and small open field study was performed to evaluate the behavior benefits of hIAIP and hypothermia working individually and together. We examined the effects of 60 mg/kg of hIAIPs injected three times after exposure of HI (right carotid artery ligation, 15 min of 8% O2) on the cognitive, motor, and locomotion function of neonatal rats through several behavior tasks. The rats were exposed to HI at postnatal day 7 (P7) and treated with normothermia (36oC for 3h) or hypothermia (30 oC for 3h) for 3 h after 1.25 h after the exposure of HI. Righting reflex assessment was performed on postnatal day 8 and 9 (P8, P9) right after the injection of the second and third dose of hIAIP (60 mg/kg) respectively. Small open field tasks were performed on postnatal day 13 and 14 ( P13, P14), and the negative geotaxis tasks were performed on postnatal day 14 (P14). In the small open field task, the cumulative time when the pups are moving, percentage of time the pups were contracting and extending their body, total distance moved and the mobility in the group treated with hIAIP only is significantly higher compared to the HI placebo group. The increased movement of rats with brain injury could be the sign of insecurities and anxiety caused by the impaired cognitive motor sensory system. We conclude that hIAIP as the adjunct treatment to therapeutic hypothermia could improve the direction, sensory and motor control of neonatal rats, but combining the treatments did not provide behavior benefits in neonatal rats after exposure to HI.
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