Peritz Scheinberg Cerebral Vascular Disease Research Laboratories, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami FL.
J Cereb Blood Flow Metab. 2023 Mar;43(3):446-459. doi: 10.1177/0271678X221137539. Epub 2022 Nov 11.
A major concern for cardiac arrest (CA) survivors is the manifestation of long-term cognitive impairments. Physical exercise (PE) is a well-established approach to improve cognitive functions under certain pathological conditions. We previously showed that PE post-CA mitigates cognitive deficits, but the underlying mechanisms remain unknown. To define neuroprotective mechanisms, we analyzed whether PE post-CA protects neurons involved in memory. We first performed a contextual fear conditioning (CFC) test to confirm that PE post-CA preserves memory in rats. We then conducted a cell-count analysis and determined the number of live cells in the hippocampus, and septal and thalamic nuclei, all areas involved in cognitive functions. Lastly, we performed RNA-seq to determine PE post-CA effect on gene expression. Following CA, exercised rats had preserved CFC memory than sham PE animals. Despite this outcome, PE post-CA did not protect hippocampal cells from dying. However, PE ameliorated cell death in septal and thalamic nuclei compared to sham PE animals, suggesting that these nuclei are crucial in mitigating cognitive decline post-CA. Interestingly, PE affected regulation of genes related to neuroinflammation, plasticity, and cell death. These findings reveal potential mechanisms whereby PE post-CA preserves cognitive functions by protecting septal and thalamic cells via gene regulation.
心脏骤停 (CA) 幸存者的一个主要关注点是长期认知障碍的表现。身体锻炼 (PE) 是一种在某些病理条件下改善认知功能的成熟方法。我们之前表明，CA 后进行 PE 可减轻认知缺陷，但潜在机制仍不清楚。为了定义神经保护机制，我们分析了 CA 后进行 PE 是否可以保护与记忆相关的神经元。我们首先进行了情境恐惧条件反射 (CFC) 测试，以确认 CA 后进行 PE 可保留大鼠的记忆。然后，我们进行了细胞计数分析，并确定了海马体、隔核和丘脑核中活细胞的数量，这些都是与认知功能相关的区域。最后，我们进行了 RNA-seq 以确定 CA 后进行 PE 对基因表达的影响。在 CA 后，进行 PE 的大鼠的 CFC 记忆比假 PE 动物要好。尽管如此，PE 并不能防止海马体细胞死亡。然而，与假 PE 动物相比，PE 改善了隔核和丘脑核中的细胞死亡，这表明这些核在减轻 CA 后认知下降方面至关重要。有趣的是，PE 影响了与神经炎症、可塑性和细胞死亡相关的基因的调节。这些发现揭示了 CA 后通过基因调节保护隔核和丘脑细胞来保存认知功能的潜在机制。
