Van Sprengel Myrthe, Butterworth Jenna, Reeson Patrick L, Brown Craig E
Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
J Cereb Blood Flow Metab. 2025 May 25:271678X251345360. doi: 10.1177/0271678X251345360.
Focal stroke leads to complex neurological disturbances with variable recovery. One explanation for this variability is that stroke disrupts local and remote neural circuits via the connectome, termed 'diaschisis'. Past studies have yielded mixed effects of stroke on dendritic structure in distant regions. However, a previous limitation was the lack of sampling specifically from neurons directly connected to those within the infarct. To overcome this, we used retrograde and anterograde trans-synaptic AAVs to examine dendritic spine density in neurons that provide inputs to, or receive outputs (pre- and post-synaptic) from primary forelimb somatosensory cortex at 1 or 6 weeks after stroke. For both pre- and post-synaptic neurons, spine density was generally lower in superficial and deep neurons in peri-infarct and motor cortex at 1 week, which recovered by 6 weeks. By contrast, no changes in spine density were observed in ipsilateral secondary somatosensory (S2) or contralateral primary somatosensory cortex at 1 week, although there was an increase in spines in select S2 neurons at 6 weeks. Our data show that some cortical connections are more disrupted by stroke than others, particularly those in peri-infarct and motor cortex which could serve as an important substrate for stroke recovery and future therapies.
局灶性中风会导致复杂的神经功能障碍，恢复情况各不相同。这种变异性的一种解释是，中风通过连接组破坏局部和远程神经回路，即所谓的“交叉性神经机能联系障碍”。过去的研究对中风对远处区域树突结构的影响得出了不同的结果。然而，以前的一个局限性是缺乏专门从与梗死灶内神经元直接相连的神经元进行采样。为了克服这一问题，我们使用逆行和顺行跨突触腺相关病毒（AAV）来检查中风后1周或6周时，向初级前肢体感皮层提供输入或从其接收输出（突触前和突触后）的神经元的树突棘密度。对于突触前和突触后神经元，梗死灶周围和运动皮层的浅层和深层神经元在1周时的棘密度通常较低，到6周时恢复。相比之下，同侧二级体感皮层（S2）或对侧初级体感皮层在1周时未观察到棘密度变化，尽管在6周时有部分S2神经元的棘有所增加。我们的数据表明，一些皮质连接受中风的影响比其他连接更大，特别是梗死灶周围和运动皮层的那些连接，这可能是中风恢复和未来治疗的重要基础。
