| Brain injury can cause devastating motor and cognitive deficits and place a tremendous social and financial burden on society. A promising avenue to pursue for brain repair is the replacement of cells lost to injury or disease. It has been previously reported that the murine medial frontal cortex (MFC) will fill with new neurons and astrocytes after it is removed by aspiration during the second postnatal week. It remains unknown whether this phenomenon will occur following a more clinically relevant injury, such as stroke, and what cellular and molecular factors mediate this process. Herein, photothrombosis was established as a practical method to induce reproducible focal ischemic lesions in neonatal mice. Following a photothrombotic stroke injury the MFC cavity does not fill with new brain cells. The immune response, which involves activation of the endogenous immune cells of the brain, microglia, and the recruitment of peripheral blood cells, was assessed using Iba1 immunohistochemistry. The Iba1+ microglia/macrophage response was more intense 24-hours following an aspiration injury compared to stroke, but this difference was no longer detected 48-hours later. Two-dimensional gel electrophoresis coupled with automated image and mass spectrometric analyses revealed fundamental protein differences between stroke and aspiration injuries. Finally, removal of the MFC three-hours after a stroke injury led to filling of the cavity with neurons and astrocytes. The microglia/macrophage and protein responses after stroke+aspiration displayed characteristics common to both stroke and aspiration injuries. The Iba1+ cell response in the grey matter was most similar to a stroke injury, whereas in the white matter, it resembled an aspiration injury. Likewise, some protein changes induced by a stroke+aspiration injury were also detected after stroke or aspiration alone. Collectively, these data indicate that aspiration and stroke injuries cause dramatically different cellular and molecular responses in the brain. A lesser microglia/macrophage response in the white matter and specific protein changes after injury may be implicated with a lack of MFC regeneration. These data provide insights into the cellular and molecular factors that regulate brain repair processes. |
