Murmu Reena P, Fordsmann Jonas C, Cai Changsi, Brazhe Alexey, Thomsen Kirsten J, Lauritzen Martin
Translational Neurobiology Group, Department of Neuroscience, Panum Institute, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
Faculty of Biology, Moscow State University, Moscow, Russia.
Front Aging Neurosci. 2019 Aug 21;11:223. doi: 10.3389/fnagi.2019.00223. eCollection 2019.
Middle cerebral artery occlusion (MCAO) induces ischemia characterized by a densely ischemic focus, and a less densely ischemic penumbral zone in which neurons and astrocytes display age-dependent dynamic variations in spontaneous Ca activities. However, it is unknown whether penumbral nerve cells respond to sensory stimulation early after stroke onset, which is critical for understanding stimulation-induced stroke therapy. In this study, we investigated the ischemic penumbra's capacity to respond to somatosensory input. We examined adult (3- to 4-month-old) and old (18- to 24-month-old) male mice at 2-4 h after MCAO, using two-photon microscopy to record somatosensory stimulation-induced neuronal and astrocytic Ca signals in the ischemic penumbra. In both adult and old mice, MCAO abolished spontaneous and stimulation-induced electrical activity in the penumbra, and strongly reduced stimulation-induced Ca responses in neuronal somas (35-82%) and neuropil (92-100%) in the penumbra. In comparison, after stroke, stimulation-induced astrocytic Ca responses in the penumbra were only moderately reduced (by 54-62%) in adult mice, and were even better preserved (reduced by 31-38%) in old mice. Our results suggest that somatosensory stimulation evokes astrocytic Ca activity in the ischemic penumbra. We hypothesize that the relatively preserved excitability of astrocytes, most prominent in aged mice, may modulate protection from ischemic infarcts during early somatosensory activation of an ischemic cortical area. Future neuroprotective efforts in stroke may target spontaneous or stimulation-induced activity of astrocytes in the ischemic penumbra.
大脑中动脉闭塞（MCAO）会引发缺血，其特征为存在一个高度缺血的病灶，以及一个缺血程度较轻的半暗带，在该半暗带中，神经元和星形胶质细胞的自发钙活动呈现出年龄依赖性的动态变化。然而，尚不清楚半暗带神经细胞在中风发作后早期是否会对感觉刺激产生反应，这对于理解刺激诱导的中风治疗至关重要。在本研究中，我们调查了缺血半暗带对体感输入的反应能力。我们在MCAO后2 - 4小时检查成年（3至4个月大）和老年（18至24个月大）雄性小鼠，使用双光子显微镜记录体感刺激在缺血半暗带诱导的神经元和星形胶质细胞钙信号。在成年和老年小鼠中，MCAO均消除了半暗带中的自发和刺激诱导的电活动，并强烈降低了半暗带中神经元胞体（35 - 82%）和神经毡（92 - 100%）的刺激诱导钙反应。相比之下，中风后，成年小鼠半暗带中刺激诱导的星形胶质细胞钙反应仅适度降低（降低54 - 62%），而老年小鼠中甚至保存得更好（降低31 - 38%）。我们的结果表明，体感刺激可诱发缺血半暗带中的星形胶质细胞钙活动。我们推测，在老年小鼠中最为突出的星形胶质细胞相对保留的兴奋性，可能在缺血皮质区域的早期体感激活过程中调节对缺血性梗死的保护作用。未来中风的神经保护研究可能针对缺血半暗带中星形胶质细胞的自发或刺激诱导活动。
