In:
Annals of Clinical and Translational Neurology, Wiley, Vol. 5, No. 4 ( 2018-04), p. 418-428
Abstract:
Traumatic cerebrovascular injury ( TCVI ), a common consequence of traumatic brain injury ( TBI ), presents an attractive therapeutic target. Because phosphodiesterase‐5 ( PDE 5) inhibitors potentiate the action of nitric oxide ( NO ) produced by endothelial cells, they are candidate therapies for TCVI . This study aims to: (1) measure cerebral blood flow ( CBF ), cerebrovascular reactivity ( CVR ), and change in CVR after a single dose of sildenafil (Δ CVR ) in chronic TBI compared to uninjured controls; (2) examine the safety and tolerability of 8‐week sildenafil administration in chronic symptomatic moderate/severe TBI patients; and as an exploratory aim, (3) assess the effect of an 8‐week course of sildenafil on chronic TBI symptoms. Methods Forty‐six subjects (31 chronic TBI , 15 matched healthy volunteers) were enrolled. Baseline CBF and CVR before and after administration of sildenafil were measured. Symptomatic TBI subjects then completed an 8‐week double‐blind, placebo‐controlled, crossover trial of sildenafil. A neuropsychological battery and neurobehavioral symptom questionnaires were administered at each study visit. Results After a single dose of sildenafil, TBI subjects showed a significant increase in global CVR compared to healthy controls ( P 〈 0.001, d = 0.9). Post‐sildenafil CVR maps showed near‐normalization of CVR in many regions where baseline CVR was low, predominantly within areas without structural abnormalities. Sildenafil was well tolerated. Clinical Global Impression ( CGI ) scale showed a trend toward clinical improvement while on sildenafil treatment. Findings Single‐dose sildenafil improves regional CVR deficits in chronic TBI patients. CVR and Δ CVR are potential predictive and pharmacodynamic biomarkers of PDE 5 inhibitor therapy for TCVI . Sildenafil is a potential therapy for TCVI .
Type of Medium:
Online Resource
ISSN:
2328-9503
,
2328-9503
DOI:
10.1002/acn3.2018.5.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2740696-9
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