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

Cells. 2023 Jan 31;12(3):457. doi: 10.3390/cells12030457.

Abstract

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 (βAPP), 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.

Keywords: inflammation; internal capsule; rat; secondary degeneration; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology
  • Gliosis* / pathology
  • Inflammation / pathology
  • Internal Capsule / pathology
  • Myelin Sheath* / pathology

Grants and funding

This research was funded by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (Finance Code 001), and Fundação de Amparo à Pesquisa do Estado do Pará (FAPESPA) (175/2014)—Brazil. R.R.L. is a researcher from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grant number 312275/2021–8.