The alignment of a 2D microscopic image stack to create a 3D image volume is an indispensable aspect of serial section electron microscopy (EM) technology, which could restore the original 3D integrity of biological tissues destroyed by chemical fixation and physical dissection. However, due to the similar texture intrasection and complex variations intersections of neural images, previous registration methods usually failed to yield reliable correspondences. And this also led to misalignment and impeded restoring the z-axis anatomical continuity of the neuron volume. In this article, inspired by human behaviors in finding correspondences, which use the topological relationship of image contents, we developed a spatial attention-based registration method for serial EM images to improve registration accuracy. Our approach combined the U-Net framework with spatial transformer networks (STN) to regress corresponding transformation maps in an unsupervised training fashion. The spatial attention (SA) module was incorporated into the U-Net architecture to increase the distinctiveness of image features by modeling its topological relationship. Experiments are conducted on both simulated and real data sets (MAS and RegCremi). Quantitative and qualitative comparisons demonstrate that our approach results in state of art accuracy (using the evaluation index of NCC, SSIM, Dice, Landmark error) and providing smooth and reliable transformation with less texture blur and unclear boundary than existing techniques. Our method is able to restore image stacks for visualization and quantitative analysis of EM image sequences.