Sanches E F, Arteni N, Nicola F, Aristimunha D, Netto C A
Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil.
Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neuroscience. 2015 Apr 2;290:581-93. doi: 10.1016/j.neuroscience.2014.12.074. Epub 2015 Jan 22.
Neonatal cerebral hypoxia-ischemia (HI) is a major cause of neurological disorders and the most common cause of death and permanent disability worldwide, affecting 1-2/1000 live term births and up to 60% of preterm births. The Levine-Rice is the main experimental HI model; however, critical variables such as the age of animals, sex and hemisphere damaged still receive little attention in experimental design. We here investigated the influence of sex and hemisphere injured on the functional outcomes and tissue damage following early (hypoxia-ischemia performed at postnatal day 3 (HIP3)) and late (hypoxia-ischemia performed at postnatalday 7 (HIP7)) HI injury in rats. Male and female 3- (P3) or 7-day-old (P7) Wistar rats had their right or left common carotid artery occluded and exposed to 8% O2 for 1.5h. Sham animals had their carotids exposed but not occluded nor submitted to the hypoxic atmosphere. Behavioral impairments were assessed in the open field arena, in the Morris water maze and in the inhibitory avoidance task; volumetric extent of tissue damage was assessed using cresyl violet staining at adult age, after completing behavioral assessment. The overall results demonstrate that: (1) HI performed at the two distinct ages cause different behavioral impairments and histological damage in adult rats (2) behavioral deficits following neonatal HIP3 and HIP7 are task-specific and dependent on sex and hemisphere injured (3) HIP7 animals presented the expected motor and cognitive deficits (4) HIP3 animals displayed discrete but significant cognitive impairments in the left hemisphere-injured females (5) HI brain injury and its consequences are determined by animal's sex and the damaged hemisphere, markedly in HIP3-injured animals.
新生儿脑缺氧缺血（HI）是神经障碍的主要原因，也是全球范围内死亡和永久性残疾的最常见原因，影响1-2/1000的足月活产儿，在早产中这一比例高达60%。莱文-赖斯模型是主要的实验性HI模型；然而，诸如动物年龄、性别和受损半球等关键变量在实验设计中仍很少受到关注。我们在此研究了性别和受损半球对大鼠早期（出生后第3天进行缺氧缺血（HIP3））和晚期（出生后第7天进行缺氧缺血（HIP7））HI损伤后功能结局和组织损伤的影响。3日龄（P3）或7日龄（P7）的雄性和雌性Wistar大鼠的右侧或左侧颈总动脉被结扎，并暴露于8%的氧气中1.5小时。假手术动物的颈动脉被暴露，但未结扎，也未暴露于低氧环境。在旷场实验、莫里斯水迷宫实验和抑制性回避任务中评估行为障碍；在完成行为评估后，使用成年期的甲酚紫染色评估组织损伤的体积范围。总体结果表明：（1）在两个不同年龄进行的HI在成年大鼠中会导致不同的行为障碍和组织学损伤；（2）新生儿HIP3和HIP7后的行为缺陷具有任务特异性，且取决于性别和受损半球；（3）HIP7动物出现了预期的运动和认知缺陷；（4）HIP3动物在左侧半球受损的雌性中表现出离散但显著的认知障碍；（5）HI脑损伤及其后果由动物的性别和受损半球决定，在HIP3损伤的动物中尤为明显。
