Tabassum Sidra, Hu Heng, Wu Silin, Huang Shuning, Yang Bosco Seong Kyu, Lee Chang-Hun, Gusdon Aaron W, Ren Xuefang S
Department of Neurosurgery, McGovern School of Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Novel Treatments for Acute Brain Injury Institute, Texas Medical Center, MSB 7.134 6431 Fannin St, Houston, TX, 77030, USA.
Transl Stroke Res. 2025 Sep 12. doi: 10.1007/s12975-025-01381-x.
Stroke is a leading cause of disability worldwide, often resulting in persistent motor, cognitive, and emotional impairments. While the hippocampus and amygdala play critical roles in post-stroke behavioral changes, specific neuronal alterations and prolonged glial responses within these regions across different stroke types remain unclear. This study investigates the behavioral, neuronal, and glial effects of subarachnoid hemorrhage (SAH), transient middle cerebral artery occlusion (tMCAO), and photothrombotic stimulation (PTS) in mice. SAH and tMCAO models exhibited significant motor deficits, spatial and recognition memory impairments, and increased anxiety- and depressive-like behaviors, whereas the PTS model showed similar motor and cognitive impairments but lacked affective (anxiety- and depressive-like) behavioral changes. Immunohistochemical analysis revealed increased overlap of tyrosine hydroxylase (TH, a dopaminergic marker) process with NeuN (a neuronal marker) in the dentate gyrus (DG) of SAH and tMCAO mice, highlighting region-specific vulnerability to ischemic damage in the hippocampus. In the amygdala, elevated overlap of TH process with NeuN in SAH and tMCAO mice suggests enhanced dopaminergic involvement in emotional dysregulation. In contrast, the PTS model did not exhibit any changes in overlap of TH process with NeuN in either the hippocampus or amygdala, consistent with the absence of affective behavioral deficits. Additionally, SAH and tMCAO models exhibited persistent astrocytic and microglial activation in the amygdala, characterized by increased intensity and density without significant morphological changes, indicative of a chronic inflammatory response. The PTS model also showed increased microglial intensity and density without overt morphological changes, suggesting a more moderate, possibly subclinical inflammatory response. These findings highlight the differential effects of stroke models on behavior, neuronal populations, and glial responses in limbic regions. The pronounced dopaminergic and glial alterations in SAH and tMCAO may underlie post-stroke emotional and cognitive disturbances.
中风是全球致残的主要原因，常常导致持续性的运动、认知和情感障碍。虽然海马体和杏仁核在中风后的行为变化中起关键作用，但不同中风类型中这些区域内特定的神经元改变和持续的胶质细胞反应仍不清楚。本研究调查了蛛网膜下腔出血（SAH）、短暂性大脑中动脉闭塞（tMCAO）和光血栓形成刺激（PTS）对小鼠行为、神经元和胶质细胞的影响。SAH和tMCAO模型表现出明显的运动缺陷、空间和识别记忆障碍以及焦虑和抑郁样行为增加，而PTS模型表现出类似的运动和认知障碍，但缺乏情感（焦虑和抑郁样）行为变化。免疫组织化学分析显示，SAH和tMCAO小鼠齿状回（DG）中酪氨酸羟化酶（TH，一种多巴胺能标记物）与NeuN（一种神经元标记物）的重叠增加，突出了海马体中区域特异性的缺血性损伤易感性。在杏仁核中，SAH和tMCAO小鼠中TH与NeuN的重叠增加表明多巴胺能参与情绪失调的增强。相比之下，PTS模型在海马体或杏仁核中TH与NeuN的重叠没有任何变化，这与缺乏情感行为缺陷一致。此外，SAH和tMCAO模型在杏仁核中表现出持续性的星形胶质细胞和小胶质细胞激活，其特征是强度和密度增加而无明显形态变化，表明存在慢性炎症反应。PTS模型也显示小胶质细胞强度和密度增加但无明显形态变化，提示有更适度、可能是亚临床的炎症反应。这些发现突出了中风模型对边缘区域行为、神经元群体和胶质细胞反应的不同影响。SAH和tMCAO中明显的多巴胺能和胶质细胞改变可能是中风后情绪和认知障碍的基础。
