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Intracortical administration of pleiotrophin in ischemic stroke: investigating functional outcomes and glial expression

  • Author / Creator
    Tanase, Celestina S.
  • Ischemic stroke is the leading cause of disability and third leading cause of death in Canada, exerting a serious burden on stroke survivors, their families, and healthcare resources. Characterized by brain damage due to loss of blood flow and oxygen supply, ischemic stroke is characterized by damage to brain tissue and chronic disability that most commonly affects sensation and movement of the upper limb. With rehabilitation, recovery from stroke is improved but is rarely complete. Current efforts focus on enhancing the extent of recovery following stroke to minimize the burden of disability on stroke survivors. This improvement in recovery could be achieved by improving the survival and regenerative capabilities of brain tissue following stroke. Pleiotrophin (PTN) is a protein that is abundantly expressed in utero and is associated with brain development by its diverse actions on different cell types existing in the brain. PTN has been documented to modulate the immune response, neuronal development, and myelination. In the present study, we sought to administer PTN to the cortical regions surrounding a stroke to investigate its effects on recovery from stroke-related functional deficits and brain responses to ischemic injury. Animals were administered an ischemic stroke affecting the forelimb and hindlimb sensorimotor cortex, followed by a delayed cortical injection of PTN. Functional deficits were assessed using two behavioural assays, the Tapered Beam task and String Pull task, which focused on measures of forelimb and hindlimb motor function. Brain tissue at varying timepoints post-stroke was investigated for PTN protein availability, markers of microglia (immune cells of the brain), astrocytes (multifunctional glial cells that form a protective scar following brain injury), and oligodendrocytes (brain cells necessary for myelination). Following stroke, only mild impairments in two sensorimotor tasks were detected. Performance in these behavioural assays was related to stroke size but unaffected by PTN treatment. Similarly, expression of the cell-specific markers was related to timepoint following stroke, but not PTN treatment. The data presented in this study cannot clearly conclude the effects of PTN treatment on functional recovery and glial responses post-stroke. Tasks more sensitive to this stroke model and investigation of cell signaling related to PTN injection in tissue are needed in future studies investigating PTN as a therapeutic target in stroke recovery.

  • Subjects / Keywords
  • Graduation date
    Spring 2023
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-ws9j-6b75
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.