The attenuation of brain edema is a major therapeutic target after traumatic brain injury (TBI). Vasopressin (AVP) is well known to play a major role in the regulation of brain water content and vasoendothelial functions and to be involved in brain edema formation. Therefore, the aim of the current study was to analyze the antiedematous efficacy of a clinically relevant, nonpeptidic AVP V1a and V2 receptor antagonists. C57Bl6 mice were subjected to controlled cortical impact (CCI) and V1a or V2 receptors were inhibited by using the highly selective antagonists SR-49059 or SR-121463A either by systemic (intraperitoneal, IP) or intracerebroventricular (ICV) application. After 24 h, brain edema, intracranial pressure (ICP), and contusion volume were assessed. Systemically applied AVP receptor antagonists could not reduce secondary lesion growth. In contrast, ICV administration of AVP V1a receptor antagonist decreased brain edema formation by 68%, diminished post-traumatic increase of ICP by 46%, and reduced secondary contusion expansion by 43% 24 h after CCI. The ICV inhibition of V2 receptors resulted in significant reduction of post-traumatic brain edema by 41% 24 h after CCI, but failed to show further influence on ICP and lesion growth. Hence, centrally applied vasopressin V1a receptor antagonists may be used to reduce brain edema formation after TBI.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321979PMC
http://dx.doi.org/10.1089/neu.2013.3274DOI Listing

Publication Analysis

Top Keywords

brain edema
28
v1a receptor
16
receptor antagonists
16
edema formation
16
brain
11
vasopressin v1a
8
traumatic brain
8
brain injury
8
avp v1a
8
antagonists reduce
8

Similar Publications

Drug Development.

Alzheimers Dement

December 2024

MEPSGEN, Seoul, Korea, Republic of (South).

Background: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Alzheon, Inc., Framingham, MA, USA.

Background: Oral ALZ-801 (valiltramiprosate), a brain-penetrant agent that inhibits amyloid-oligomer formation is being evaluated in a fully enrolled APOLLOE4 Phase 3 trial in APOE4/4 homozygotes with Early Alzheimer's disease (AD). ALZ-801 effects on plasma AD biomarkers were evaluated in a 104-week Phase 2 study in APOE4-carriers with CSF+ AD biomarkers. APOE4 is a major risk factor for amyloid-related imaging abnormalities (ARIA) in AD patients.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Vanderbilt University Medical Center, Nashville, TN, USA.

Background: We report the case of a 79-year-old woman with Alzheimer's disease who enrolled in a clinical study of lecanemab. After the third, biweekly infusion she suffered a seizure followed by aphasia and progressive encephalopathy. Magnetic resonance imaging revealed multifocal cerebral edema and an increased burden of cerebral microhemorrhages compared to pre-trial imaging.

View Article and Find Full Text PDF

Drug Development.

Alzheimers Dement

December 2024

Alzheon, Inc., Framingham, MA, USA.

Background: ALZ-801 (valiltramiprosate), an oral brain-penetrant amyloid-oligomer inhibitor in Phase 3 testing in APOE4/4 homozygotes (APOLLOE4 trial). A 2-year Phase 2 biomarker study was completed evaluating ALZ-801 (265 mg BID) on plasma biomarkers, MRI, cognition, and clinical benefit in EAD APOE4 carriers. At trial end, subjects could enroll in a 1-year long-term extension with an ongoing biomarker and cognition analysis.

View Article and Find Full Text PDF

Background: Elevated intracranial pressure (ICP) is a potentially life-threatening condition requiring prompt intervention. While both mannitol and hypertonic saline (HTS) are commonly used hyperosmotic agents for treating elevated ICP, there is insufficient evidence comparing their renal safety profiles and overall effectiveness. This study protocol outlines a pragmatic randomized trial to compare protocol-based 11.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!