Research ReportMicroglia activation along the corticospinal tract following traumatic brain injury in the rat: A neuroanatomical study

Traumatic injury to the brain often manifests itself symptomatically and structurally long after the traumatic event. The cellular basis of this complex response is not completely understood. However, we hypothesized that microglia might contribute to the brain-wide process. To test this hypothesis, we employed optical and electron microscopy to study the microglia in rat brains up to 2 months after digitally controlled cortical impact (CCI) to produce traumatic brain injury (TBI). We also used antibodies against ED-1 and Iba-1, respectively, as markers for activated and resting microglia. ED-1 positive microglial cells are observed accompanying the entire corticospinal tract (CST) on the injured side, but not the control, contralateral side of the brain at 2 months. In this case, ED-1 and Iba-1 were observed to co-localize uniquely on the injured side of the brain. At earlier times following CCI, ultrastructural studies reveal that microglial cells have very irregular shapes and have many processes that intermingle with degenerating nerve axons of the CST in the hindbrain pyramids. These cells appear to be engulfing degenerating myelinated axons. The debris within the cells is converted to lipofuscin, the antigen for the ED-1 antibody, and remains in the cell cytoplasm throughout the life of the cell. We conclude, as hypothesized, that microglia are critical cellular components. Based on observed close association with myelin degeneration, interdigitating activated microglia may be contributing to damage control. Finally, based on the close neuroanatomical relationship between the lesioned corticospinal tract and the wide distribution of activated microglia, primary signals from CST neurons per se, may be directing microglial responses along the entire damaged rat neuroaxis. The role of persistent activation of microglia has not been determined.

► Optical and electron microscopy was used to study microglia influence on traumatic brain injury. ► Two months after cortical injury microglial cells are observed along the entire corticospinal tract. ► Electron microscopic work shows microglia engulfing degenerating myelinated axons. ► Microglia are critical cellular components of the complex response of the brain to injury. ► Signals from corticospinal tract neurons may be directing microglial responses along the entire damaged neuroaxis