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Title: Role of folates in normal and hydrocephalic fetal brain development
Author: Requena Jimenez, Alicia
ISNI:       0000 0004 5990 6229
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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Brain cerebrospinal fluid (CSF) bulk flow is maintained thanks to a balance between CSF secretion from the choroid plexus and CSF absorption by arachnoid villi, where it drains into nearby blood vessels, thereby reaching the general blood circulation. Congenital hydrocephalus starts during the first trimester of pregnancy with impeded CSF flow, and consequent CSF build-up within the brain ventricles. This event is followed by CSF compositional changes, increased intracranial pressure, and, if untreated, brain damage and fetal death. Previous research has revealed a unique folate delivery system which serves the developing cerebral cortex. Abnormal folate provision due to impairment of this system was directly connected to a decrease in a CSF folate enzyme: 10-Formyl-Tetrahydrofolate dehydrogenase (FDH). In light of these findings, low FDH was linked with folate deficiency and the poor cortical development found in congenital hydrocephalus. In this context, investigations were carried out to ascertain whether folates in the presence and absence of the folate enzyme FDH are beneficial for fetal brain development. The current study also aims to investigate the FDH -folate delivery system in the fetal brain in order to understand its role in CNS development and its relationship to currently known folate transport mechanisms (FRα). Furthermore, we hypothesize that folates may prevent congenital hydrocephalus through a re-establishment of CSF drainage and flow circulation at the level of the arachnoid membrane/villi. This assumption implies that the leptomeninge arachnoid may also be dysfunctional in the hydrocephalic brain due to a variation in hydrocephalic CSF composition (folates). Finally, an overall metabolic pathway analysis of the constituents uniquely present in abnormal CSF, hence missing in normal CSF, and vice versa, was carried out to establish associations with suggested activated and inactivated biological processes during congenital hydrocephalus.
Supervisor: Miyan, Jaleel ; Gigg, John Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: hydrocephalus ; fetal brain development ; folate