丙戊酸
创伤性脑损伤
医学
病变
药代动力学
安慰剂
麻醉
生理盐水
临床试验
脑损伤
内科学
外科
病理
癫痫
精神科
替代医学
作者
Glenn K. Wakam,Ben E. Biesterveld,Manjunath P. Pai,Michael T. Kemp,Rachel O’Connell,Krishani Rajanayake,Kiril Chtraklin,Claire A Vercruysse,Hasan B. Alam
出处
期刊:The journal of trauma and acute care surgery
[Ovid Technologies (Wolters Kluwer)]
日期:2021-11-01
卷期号:91 (5): 867-871
被引量:3
标识
DOI:10.1097/ta.0000000000003136
摘要
We lack specific treatments for traumatic brain injury (TBI), which remains the leading cause of trauma-related morbidity and mortality. Treatment with valproic acid (VPA) improves outcomes in models of severe TBI with concurrent hemorrhage. However, it is unknown if VPA will have similar benefits after isolated nonlethal TBI, which is the more common clinical scenario. The goal of this study was to evaluate the effect of VPA treatment in a preclinical isolated TBI swine model on neurologic outcomes and brain lesion size and to perform detailed pharmacokinetic analyses for a future clinical trial.Yorkshire swine (n = 10; 5/cohort) were subjected to TBI (8-mm controlled cortical impact). An hour later, we randomized them to receive VPA (150 mg/kg) or saline placebo (control). Neuroseverity scores were assessed daily (0 [normal] to 36 [comatose]), brain lesion size was measured on postinjury 3, and serial blood samples were collected for pharmacokinetic studies.Physiologic parameters and laboratory values were similar in both groups. Valproic acid-treated animals demonstrated significantly better neuroseverity scores on postinjury 1 (control, 9.2 ± 4.4; VPA, 0 ± 0; p = 0.001). Valproic acid-treated animals had significantly smaller brain lesion sizes (mean volume in microliter: control, 3,130 ± 2,166; VPA, 764 ± 208; p = 0.02). Pharmacokinetic data confirmed adequate plasma and tissue levels of VPA.In this clinically relevant model of isolated TBI, a single dose of VPA attenuates neurological impairment and decreases brain lesion size.
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