The Novel Nitric Oxide Synthase Inhibitor 4-amino-tetrahydro-L-biopterine Prevents Brain Edema Formation and Intracranial Hypertension following Traumatic Brain Injury in Mice
| العنوان: | The Novel Nitric Oxide Synthase Inhibitor 4-amino-tetrahydro-L-biopterine Prevents Brain Edema Formation and Intracranial Hypertension following Traumatic Brain Injury in Mice |
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| المؤلفون: | Nikolaus Plesnila, Raimund Trabold, Reinhard Schinzel, Lothar Schilling, Klaus Zweckberger, Nicole A. Terpolilli, Frank Tegtmeier |
| المصدر: | Journal of Neurotrauma. 26:1963-1975 |
| بيانات النشر: | Mary Ann Liebert Inc, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Middle Cerebral Artery, NOS inhibitor, Traumatic brain injury, Cerebral arteries, Brain Edema, Pharmacology, Nitric oxide, Rats, Sprague-Dawley, Mice, chemistry.chemical_compound, Organ Culture Techniques, medicine, Animals, Enzyme Inhibitors, Intracranial pressure, biology, Brain edema, business.industry, Recovery of Function, medicine.disease, Biopterin, Immunohistochemistry, Rats, Mice, Inbred C57BL, Nitric oxide synthase, chemistry, Vasoconstriction, Basilar Artery, Brain Injuries, Anesthesia, biology.protein, Neurology (clinical), Intracranial Hypertension, Nitric Oxide Synthase, business |
| الوصف: | Brain edema formation, resulting in increased intracranial pressure (ICP), is one of the most deleterious consequences of traumatic brain injury (TBI). Nitric oxide (NO) has previously been shown to be involved in the damage of the blood-brain barrier (BBB) and, thus, in the formation of post-traumatic brain edema; however, this knowledge never resulted in a clinically relevant therapeutic option because available NO synthase inhibitors have serious side effects in man. The aim of the current study was to investigate the therapeutic efficacy of VAS203, a novel tetrahydrobiopterine (BH3)-based NOS inhibitor, in experimental TBI. When added to isolated vessels rings obtained from rat basilar and middle cerebral arteries (n = 32-35) VAS203 showed the same vasoconstrictive effect as the classical NO synthase inhibitor L-(G)-nitro-arginine-methylester (L-NAME). VAS203 passed the BBB both in healthy and traumatized mouse brain (C57/BL6, n = 5 per group) and did not show any systemic side effects at therapeutic concentrations. When administered 30 min after experimental TBI (controlled cortical impact, 2.2 mg/kg/min i.v., n = 7 per group), VAS203 prevented any further increase in ICP or deterioration of cerebral blood flow. This effect was dose-dependent and long-lasting (i.e., 24 h after trauma, brain edema formation was still significantly reduced [-40%, p0.008; n = 7 per group] and functional improvements were present up to 7 days after TBI [p0.02 on post-trauma day 6; n = 8 per group]). Therefore, VAS203 may represent a promising candidate for the treatment of acute intracranial hypertension following TBI. |
| تدمد: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2008.0853 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2adbe353ba6ab6d79da32eab0c2272a5 https://doi.org/10.1089/neu.2008.0853 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2adbe353ba6ab6d79da32eab0c2272a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15579042 08977151 |
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| DOI: | 10.1089/neu.2008.0853 |