Behavioral Neuroscience Division, Department of Psychology, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT 06269, USA.
Division of Neonatology, Department of Pediatrics, University of Minnesota, 516 Delaware Street S.E. Minneapolis, MN 55454, USA.
Brain Sci. 2014 Apr 2;4(2):240-72. doi: 10.3390/brainsci4020240.
Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36-38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD-a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI.
缺氧缺血(HI;血液/氧气供应减少)在患有严重出生并发症的婴儿中很常见,例如产程延长和脐带脱垂,以及早产儿(<37 周妊娠龄;GA)。大多数情况下,HI 可导致皮质和皮质下损伤形式的脑损伤,以及随后的认知/行为缺陷。常见的损害领域是工作记忆,这可能与发育障碍的发生率升高有关。为了进一步描述这些临床问题,当前的研究描述了来自产后(P)7 诱导的 HI 啮齿动物模型的数据,该年龄与足月(GA 36-38)人类相当。具体来说,我们试图使用八臂放射状水迷宫范式评估工作记忆。研究 1 使用该范式的修改版本,该版本需要通过逐步增加空间记忆的难度任务以及更多的每日试验来增加学习机会,从而逐步改变空间记忆。结果令人惊讶,仅在引入测试前延迟的最后一个也是最困难的条件下,发现 HI 存在轻微缺陷。研究 2 再次使用修改后的放射臂迷宫,但从最困难的条件开始,并且仅进行一次每日测试试验。在这里,结果是预期的,并且在所有星期都显示出强大而一致的 HI 缺陷。综合结果表明,如果以分级多试验格式呈现,雄性 HI 大鼠可以学习困难的空间工作记忆任务,但表现不佳,如果任务具有较高的初始记忆需求,则表现不佳且似乎无法改善。在两项研究中,雄性 HI 大鼠在整个测试过程中均表现出冲动特征,表现为尽管错误更多,但选择潜伏期却减少。行为结果的这一方面与冲动一致,冲动是患有 HI 损伤的儿童中 ADHD 的核心症状之一。总体发现表明,任务特异性行为改变对于适应患有新生儿 HI 后认知障碍的儿童的记忆缺陷至关重要。