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Trauma to the central and peripheral nervous systems such as traumatic brain injury, spinal cord injury and stroke leads to significant loss of function. This poses a considerable burden for patients as this loss of function often leads to lifelong disabilities due to the limited regenerative capacity of nervous tissue. Historically, astrocytes, the most abundant type of glial cell that resides in the central and peripheral nervous systems, have been thought to predominantly inhibit nerve growth after injury. However, recent advancements have discovered the importance of astrocytes and their integral role in recovery following spinal cord injury. In particular, the manipulation of astrocyte pro- (A1) and anti- (A2) inflammatory phenotypes can provide valuable insights into astrocyte behavior, migration and wound healing potential. A1 and A2 reactive states can be induced through cytokine activation. The combination of interleukin (IL)-1α, tumor necrosis factor (TNF) and complement component 1q (C1q) has shown to exhibit the strongest A1, or neurotoxic phenotype. Interleukin-10 has shown to induce the A2, or neuroprotective phenotype. Research has also shown that A1 reactive astrocytes lose the ability to promote neuron survival, regeneration and outgrowth, and induce the death of neurons and oligodendrocytes. Additionally, the discovery of cell migration effects through tumor-derived matrices supports a novel approach in inducing astrocyte reactivity through matrix activation. Our research describes a methodology to discover and eventually reprogramme astrocyte behavior to promote neuroprotective phenotypes through cellular interaction with matrix glycoproteins. Through a migration scratch assay, we were able to explore the A1- and A2- inducing nature of glioblastoma stem cell (GSC) matrix on astrocytes, specifically the various glycoproteins composing each stem cell matrix as compared to the baseline cytokine activation. After quantifying results, cell migration was found to vary between each GSC line, leading us to infer that GSC glycoproteins promote astrocyte activation. Further quantification through qPCR will allow us to examine the markers within each GSC matrix and confirm which proteins specifically induce A1 and A2 activity. With this knowledge, we will be better able to understand and manipulate astrocyte neuroprotective responses to neural injury, and develop effective therapeutics to promote wound healing. This project was conducted partly in support from the Undergraduate Research at University of Massachusetts Amherst, and funding from the National Institute of Health.
Raman et al. (Fri,) studied this question.