School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, The University of Newcastle, University Dr, Callaghan, NSW 2308, Australia.
Hunter Medical Research Institute, Lot 1, Kookaburra Cct, New Lambton Heights, NSW 2305, Australia.
Int J Mol Sci. 2020 Jun 26;21(12):4563. doi: 10.3390/ijms21124563.
Cognitive impairment is common after stroke, and disturbances in hippocampal function are often involved, even in remote non-hippocampal injuries. In terms of hippocampal function, growth hormone (GH) is known to affects plasticity and cognition. We aimed to investigate whether GH treatment after an experimental cortical stroke could enhance remote hippocampal plasticity and the hippocampal-dependent visual discrimination task. C57BL6 male mice were subjected to cortical photothrombotic stroke. Stroke mice were then treated with either saline or GH at 48 h after occlusion for 28 days. We assessed learning and memory using mouse touchscreen platform for the visual discrimination task. We also evaluated markers of neural progenitor cells, synaptic plasticity and cerebrovascular remodelling in the hippocampal formation. GH treatment significantly improved the performance on visual discrimination task after stroke. We observed a concomitant increased number of bromodeoxyuridine-positive cells in the dentate gyrus of the hippocampus. We also detected increased protein levels and density of doublecortin, a neuronal precursor cells marker, as well as glutamate receptor 1 (GLuR1), a synaptic marker. These findings provide further neurobiological evidence for how GH treatment could be used to promote hippocampal plasticity in a remote region from the initial cortical injury, and thus enhance cognitive recovery after stroke.
认知障碍在中风后很常见，海马功能障碍通常也会涉及，即使是在远处的非海马损伤中也是如此。就海马功能而言，已知生长激素（GH）会影响可塑性和认知。我们旨在研究实验性皮质性中风后 GH 治疗是否可以增强远程海马可塑性和海马依赖性视觉辨别任务。雄性 C57BL6 小鼠接受皮质光血栓性中风。中风后 48 小时闭塞 28 天，用生理盐水或 GH 治疗中风小鼠。我们使用小鼠触摸屏平台评估学习和记忆，用于视觉辨别任务。我们还评估了海马结构中神经祖细胞、突触可塑性和脑血管重塑的标志物。GH 治疗可显著改善中风后视觉辨别任务的表现。我们观察到海马齿状回中 BrdU 阳性细胞数量增加。我们还检测到神经元前体细胞标志物双皮质素和突触标志物谷氨酸受体 1（GLuR1）的蛋白水平和密度增加。这些发现为 GH 治疗如何促进初始皮质损伤远处区域的海马可塑性以及增强中风后的认知恢复提供了进一步的神经生物学证据。
