Figure 1.

Schematic of an intact gyrencephalic brain.

The picture shows the gyri, sulci, six layers of cortical neurons (red triangles with yellow nuclei) in gray matter (GM) and neuronal density dependent projections into white matter (WM) with normal astrocytes (red stars), highly ramified resting (filled blue arrow) and primed microglia (open blue arrow) in (A). After penetrating traumatic brain injury (PTBI), represented by a cortical tissue penetration the penumbra surrounding the injury core is replete with proinflammatory-activated microglia (orange arrow). Activated microglial pyroptosis (secondary damage) in penumbra causing cortical thinning (red arrow) and manifest as ventriculomegaly (VM). Persistent axonal debris and chronic microglial activation mediate toxic inflammation fueling tissue loss years after injury (B). Stereotaxic transplantation of human neural stem cells (green shapes) in penumbra would provide a two-in-one solution, a source of cells to replace lost cell types, resolve chronic microglial activation preventing further tissue loss (C).