Abstract

Abstract Modern optical imaging techniques provide powerful tools for observing cortical structure and functions at high resolutions. Various skull windows have been established for different applications of cortical imaging, and each has its advantages and limitations. Most critical of the limitations, none of the current skull windows is suitable for observing the responses to some acute craniocerebral injuries on a large scale and at high resolution. Here, we developed a “Through-Intact-Skull (TIS) window” that enables the observation of an immune response on a bilateral cortical scale and at single-cell resolution after traumatic brain injury without affecting the pathological environment of the brain. The TIS window also has the advantages of craniotomy-freeness, centimeter-field of view, synaptic resolution, large imaging depth, long-term observation capability, and suitability for awake mice. Therefore, the TIS window is a promising new approach for intravital cortical microscopy in basic research in neuroscience.