Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ann Neurol. 2011 Jul;70(1):121-32. doi: 10.1002/ana.22386.
Most patients with stroke caused by middle cerebral artery occlusion (MCAO) show cognitive deficit that is generally regarded as resulting from damage to the cerebral cortex rather than the hippocampus. Whether MCAO induces hippocampal damage and whether this contributes to the cognitive defects remains unclear. Here we investigate the hippocampal damage and its correlation to cognitive defects after exclusively unilateral MCAO and the underlying mechanism for that damage.
Patients were assessed for hippocampal damage by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), and the Mini Mental-Status Evaluation (MMSE) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess for cognitive defects.
We provide the first evidence that patients with exclusively unilateral MCAO showed hippocampal damage characterized by an infarct-size-independent atrophy and alterations in neuronal and glial metabolites in the ipsilateral hippocampus, in parallel with cognitive impairment. Rodent MCAO also induced delayed shrinkage and pyramidal neuronal death in the ipsilateral hippocampus and an impairment of hippocampal-dependent spatial memory. Blocking Gap junctional communication (GJC) with carbenoxolone or downregulation of connexin43 (Cx43) significantly increased the survival of the pyramidal neurons in the ipsilateral hippocampus and improved behavioral scores. Furthermore, Cx43 heterozygous mice showed reduced shrinkage and metabolite abnormality in ipsilateral hippocampus after MCAO.
Astroglial GJC plays a significant role in MCAO-induced remote hippocampal damage and cognitive impairment. It might be possible to improve the cognition in patients with MCAO by manipulating interastrocytic communication via the gap junction channels.
大多数由大脑中动脉闭塞（MCAO）引起的中风患者表现出认知缺陷，通常认为这种缺陷是由于大脑皮层而不是海马体受损所致。MCAO 是否会引起海马体损伤，以及这种损伤是否会导致认知缺陷尚不清楚。在这里，我们研究了单纯性 MCAO 后海马体的损伤及其与认知缺陷的相关性，以及这种损伤的潜在机制。
通过磁共振成像（MRI）和磁共振血管造影（MRA）评估患者的海马体损伤情况，并用简易精神状态检查表（MMSE）和 Rey 听觉言语学习测验（RAVLT）评估认知缺陷。
我们首次提供了证据，证明单纯性 MCAO 患者表现出海马体损伤，其特征为梗死灶大小无关的萎缩和同侧海马体神经元和神经胶质代谢物的改变，同时伴有认知障碍。鼠 MCAO 还导致同侧海马体的延迟性萎缩和锥体神经元死亡，以及海马体依赖性空间记忆受损。用 carbenoxolone 阻断缝隙连接通讯（GJC）或下调连接蛋白 43（Cx43）显著增加了同侧海马体锥体神经元的存活率，并改善了行为评分。此外，Cx43 杂合子小鼠在 MCAO 后同侧海马体的萎缩和代谢物异常减少。
星形胶质细胞 GJC 在 MCAO 引起的远隔海马体损伤和认知障碍中起着重要作用。通过操纵缝隙连接通道的星形胶质细胞间通讯，可能改善 MCAO 患者的认知能力。
