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To date nothing is known about the subacute phase of neurodegeneration following injury in invertebrates. Among few clues available are the results published by our group reporting hemocytes and activated glial cells at chronic and acute phases of the lesion. In vertebrates, glial activation and recruitment of immunological cells are crucial events during neurodegeneration. Here, we aimed to study the subacute stage of neurodegeneration in the crab Ucides cordatus, investigating the cellular/molecular strategy employed 48 hours following ablation of the protocerebral tract (PCT). We also explored the expression of nitric oxide (NO) and histamine in the PCT during this phase of neurodegeneration. Three immune cellular features which seem to characterize the subacute phase of neurodegeneration were revealed by: 1) the recruitment of granulocytes and secondarily of hyalinocytes to the lesion site (inducible NO synthase- and histamine-positive cells); 2) the attraction of a larger number of cells than observed in the acute phase; 3) the presence of activated glial cells as shown by the round shaped nuclei and increased expression of glial fibrillary acidic protein. We suggest that molecules released from granulocytes in the acute phase attract the hyalinocytes thus moving the degeneration process to the subacute phase. The importance of our study resides in the characterization of cellular and biochemical strategies peculiar to the subacute stage of the neurodegeneration in invertebrates. Such events are worth studying in crustaceans because in invertebrates this issue may be addressed with less interference from complex strategies resulting from the acquired immune system.