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The Role of Estrogen (Estradiol and Estrone) on the Development of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Crago, Elizabeth (2012) The Role of Estrogen (Estradiol and Estrone) on the Development of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Delayed cerebral ischemia (DCI) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH). Recent evidence has suggested that biochemical mediators alter cerebral perfusion resulting in neurological decline. Estrogens (estrone–E1 and estradiol–E2) are mediators with demonstrated neuroprotective properties that could be implicated in DCI. The impact of E1 or E2 on outcomes in humans following aSAH has been understudied. The purpose of this study was to examine the association between E1 and E2 levels and DCI following aSAH. Plasma and cerebral spinal fluid (CSF) samples collected after hemorrhage on 99 acute, adult aSAH patients admitted to the Neurovascular ICU enrolled in a NIH funded study-RO1NR004339. Three plasma and up to 5 CSF samples were selected for E1 and E2 analysis from each patient representing early(1–4), middle(4-6) and late(7-10) days after hemorrhage and were assayed using liquid chromatography-tandem mass spectrometry. DCI was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. Statistical analysis included detailed descriptive, group based trajectory and multiple logistic regression using SAS v9.2.
Group based trajectory identified 2 groups over time for both plasma E1 (61.4% E1-high and 38.6% E1-low) and E2 (48% E2-high and 52% E2-low) values using censored normal model. Weighted Chi Square analysis identified differences between trajectory groups by gender(p=.02), menopause(.05), age(p<.001) and fisher grade(p=.008) with patients in the high E1 group having higher severity of injury than those in the low E1 group. Likewise, patients with higher HH (E1 p=.01, E2 p=.02) and Fisher (E1 p=.008, E2 p=.08) were more likely to have higher plasma estrogen levels. The presence of DCI was also significantly associated with higher levels of plasma E1(p=.002) and E2(p=.03) and the high E1 trajectory group(p=.09). CSF was evaluated in 36 aSAH patients. Similar correlations between higher E1 and E2 CSF concentrations and severity of injury and DCI were noted. These results provide the first clinical evidence that E1 and E2 concentrations in plasma and CSF are associated with severity of injury and DCI and provide incentive for future studies to clarify the potential role of estrogen in ischemic complications after aSAH.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Crago, Elizabethecrago@pitt.eduECRAGO
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSherwood, Paulaprs11@pitt.eduPRS11
Committee MemberPoloyac, Samuelpoloyac@pitt.eduPOLOYAC
Committee MemberBender, Catherinecbe100@pitt.eduCBE100
Committee MemberBalzer,
Committee MemberRen, Dianxudir8@pitt.eduDIR8
Date: 30 April 2012
Date Type: Publication
Defense Date: 16 April 2012
Approval Date: 30 April 2012
Submission Date: 26 April 2012
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 130
Institution: University of Pittsburgh
Schools and Programs: School of Nursing > Nursing
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: subarachnoid hemorrhage, aneurysm, estrogen, estradiol, estrone, delayed cerebral ischemia
Date Deposited: 30 Apr 2012 14:51
Last Modified: 15 Nov 2016 13:57


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