Astrocytosis, Inflammation, Axonal Damage and Myelin Impairment in the Internal Capsule following Striatal Ischemic Injury

Secondary degeneration is defined as a set of destructive events that damage cells and structures that were initially spared or only peripherally affected by the primary insult, constituting a key factor for functional impairment after traumatic brain injury or stroke. In the present study, we evaluated the patterns of astrocytosis, inflammatory response, axonal damage and oligodendrocytes/myelin impairment in the internal capsule following a focal injection of endothelin-1 (ET-1) into the dorsal striatum. Animals were perfused at 1, 3 and 7 post-lesion days (PLD), and tissue was processed to immunohistochemistry for neutrophils (MBS1), macrophages/microglia (ED1), astrocytes (GFAP), axonal lesion (beta APP), oligodendrocytes (Tau) and myelin (MBP). A significant number of neutrophils was observed at 1PLD, followed by intense recruitment/activation of macrophages/microglia at 3PLD and astrocytic reaction with a peak at 7PLD. Oligodendrocyte damage was pronounced at 3PLD, remaining at 7PLD. Progressive myelin impairment was observed, with reduction of immunoreactivity at 7PLD. Axonal lesion was also identified, mainly at 7PLD. Our results indicate that acute inflammatory response elicited by the ischemic insult in the striatum can be associated with the axonal impairment and damage of both oligodendrocytes and myelin sheath identified in the internal capsule, which may be related to loss of tissue functionality observed in secondary degeneration.

Automated summary

Secondary degeneration refers to a series of destructive events that occur in cells and structures initially unaffected by primary injury, and it is a critical factor in functional impairment following traumatic brain injury or stroke. This study investigated the effects of endothelin-1 injection on astrocytosis, inflammatory response, axonal damage, and oligodendrocyte/myelin impairment in the internal capsule. Neutrophils were observed at 1 day post-lesion (PLD), followed by macrophage/microglia activation at 3 PLD and peak astrocytic reaction at 7 PLD. Oligodendrocyte damage was notable at 3 PLD and persisted at 7 PLD. Progressive myelin impairment and axonal lesion were also observed, particularly at 7 PLD. These findings suggest that the acute inflammatory response triggered by ischemic insult in the striatum may contribute to axonal impairment, oligodendrocyte damage, and myelin sheath degradation in the internal capsule, which ultimately leads to tissue dysfunction in secondary degeneration.