Gilmer Lesley K, Roberts Kelly N, Scheff Stephen W
Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
J Neurotrauma. 2008 Jun;25(6):593-602. doi: 10.1089/neu.2007.0477.
Traumatic brain injury (TBI) results in an accumulation of edema and loss of brain tissue. Progesterone (PROG) has been reported to reduce edema and cortical tissue loss in a bilateral prefrontal cortex injury. This study tests the hypothesis that PROG is neuroprotective following a unilateral parietal cortical contusion injury (CCI). Adult male Sprague-Dawley rats were subjected to a moderate unilateral TBI using the CCI model. Rats were given 8 mg/kg PROG 15 min post-injury with four subsequent injections (6 h, and days 1, 2, and 3). Edema was determined 3 days post-injury, while cortical tissue sparing was also evaluated at 7 days post-injury. Animals were injured and given one of four treatments: (I) vehicle; (II) low dose: 8 mg/kg PROG; (III) high dose: 16 mg/kg PROG; (IV) tapered: 8 mg/kg PROG. Animals were given an initial injection within 15 min, followed by five injections (6 h, and days 1, 2, 3, and 4). Group IV received two additional injections (4 mg/kg on day 5; 2 mg/kg on day 6). PROG failed to alter both cortical edema and tissue sparing at any dose. Failure to modify two major sequelae associated with TBI brings into question the clinical usefulness of PROG as an effective treatment for all types of brain injury.
创伤性脑损伤（TBI）会导致脑水肿积聚和脑组织损失。据报道，孕酮（PROG）可减轻双侧前额叶皮质损伤中的水肿和皮质组织损失。本研究检验了以下假设：PROG在单侧顶叶皮质挫伤性损伤（CCI）后具有神经保护作用。成年雄性Sprague-Dawley大鼠采用CCI模型进行中度单侧TBI。大鼠在受伤后15分钟给予8mg/kg PROG，随后进行四次注射（6小时、第1天、第2天和第3天）。在受伤后3天测定水肿情况，同时在受伤后7天评估皮质组织保留情况。动物受伤后接受四种治疗之一：（I）赋形剂；（II）低剂量：8mg/kg PROG；（III）高剂量：16mg/kg PROG；（IV）递减剂量：8mg/kg PROG。动物在15分钟内接受初次注射，随后进行五次注射（6小时、第1天、第2天、第3天和第4天）。第四组接受两次额外注射（第5天4mg/kg；第6天2mg/kg）。任何剂量的PROG均未能改变皮质水肿和组织保留情况。未能改善与TBI相关的两个主要后遗症，这让人质疑PROG作为治疗所有类型脑损伤的有效疗法的临床实用性。
