Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury
By Jill Faulkner, J. Herrmann, M. J. Woo, K. Tansey, N. Doan, M. Sofroniew. Journal of Neuroscience, 2004
1,581 citations recorded by the source corpus.
Reactive astrocytes are prominent in the cellular response to spinal cord injury (SCI), but their roles are not well understood. We used a transgenic mouse model to study the consequences of selective and conditional ablation of reactive astrocytes after stab or crush SCI. Mice expressing a glial fibrillary acid protein-herpes simplex virus-thymidine kinase transgene were given mild or moderate SCI and treated with the antiviral agent ganciclovir (GCV) to ablate dividing, reactive, transgene-expressing astrocytes in the immediate vicinity of the SCI. Small stab injuries in control mice caused little tissue disruption, little demyelination, no obvious neuronal death, and mild, reversible functional impairments. Equivalent small stab injuries in transgenic mice given GCV to ablate reactive astrocytes caused failure of blood-brain barrier repair, leukocyte infiltration, local tissue disruption, severe demyelination, neuronal and oligodendrocyte death, and pronounced motor deficits. Moderate crush injuries in control mice caused focal tissue disruption and cellular degeneration, with moderate, primarily reversible motor impairments. Equivalent moderate crush injuries combined with ablation of reactive astrocytes caused widespread tissue disruption, pronounced cellular degeneration, and failure of wound contraction, with severe persisting motor deficits. These findings show that reactive astrocytes provide essential activities that protect tissue and preserve function after mild or moderate SCI. In nontransgenic animals, crush or contusion SCIs routinely exhibit regions of degenerated tissue that are devoid of astrocytes. Our findings suggest that identifying ways to preserve reactive astrocytes, to augment their protective functions, or both, may lead to novel approaches to reducing secondary tissue degeneration and improving functional outcome after SCI.
Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/e265cef73b368b145c3d8bd499d0564d86735398
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Citations in the corpus
- Spinal cord injury: molecular mechanisms and therapeutic interventions (2023, background): “After using GFAP-TK transgenic mice and ganciclovir administration to ablate dividing reactive astrocytes, failure of blood‒brain barrier repair, leukocyte infiltration, demyelination, neural cell death, and functional deficits were observed.(174) In STAT3 conditional knockout transgenic mice, the a”
- Astrocyte crosstalk in CNS inflammation (2020, background): “Thus, it is not surprising that the communication between astrocytes and CNSresident or CNS-infiltrating cells plays a central role in tissue physiology and pathology (Anderson et al., 2016; Anderson et al., 2018; Chao et al., 2019; Faulkner et al., 2004; Liddelow et al., 2017; Lin et al., 2017; Nag”
- Glial inhibition of CNS axon regeneration (2006, background): “Some populations of astrocytes might even support axon regrowt”
- Astrocytes: biology and pathology (2009, background): “Genetic animal models are providing evidence for ways in which loss or attenuation of reactive astrocyte functions might worsen outcome after various kinds of CNS insults, for example, through excitotoxic neurodegeneration due to failure or attenuation of glutamate uptake [33, 198, 234] or increased”
- Regeneration beyond the glial scar (2004, background): “The astrocyte response to injury is referred to as reactive gliosis (more glia) but in fact, in most types of injury, the actual amount of glial cell division is relatively small and confined to the immediate penumbra surrounding the lesion cor”
- The bright side of the glial scar in CNS repair (2009, background): “These studies revealed that removal of astrocytes from the site of damage leads to larger lesions, local tissue disruption, severe demyelination and neuron and oligodendrocyte deat”
- From basics to clinical: a comprehensive review on spinal cord injury. (2014, background): “These sequence of events consequently lead to worst functional outcomes (Faulkner et al., 2004; Okada et al., 2006).”
- Genomic Analysis of Reactive Astrogliosis (2012, background): “Conversely, elegant work involving ablation of reactive astrocytes has demonstrated that reactive astrocytes are crucial for withstanding insult and improving recovery after CNS trauma, after ischemia, and in experimental autoimmune encephalomyelitis (Bush et al., 1999; Faulkner et al., 2004; Voskuh”
- Astrocyte activation and reactive gliosis (2005, background): “GFAP-driven expression of herpes simplex virus thymidine kinase and administration of ganciclovir (Bush et al., 1999; Faulkner et al., 2004).”
- Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury (2008, methodology): “We conducted basic surgical procedures and postoperative care for SCI subjects as described previousl”
- The role of inflammation in CNS injury and disease (2006, background): “…for repair and recovery, but in fact this increases neuronal loss from the injury site and inhibits repair of the BBB and axonal remyelination (Faulkner et al., 2004), partly because astrocytes produce neurotrophic factors such as nerve growth factor and brain-derived growth factor that are…”
- Astrocyte reactivity and reactive astrogliosis: costs and benefits. (2014, background): “creased neuroprotection and, in some situations, in achieving relative isolation/sequestering of the toxic and potentially expanding lesion area from the rest of the CNS (71, 154, 249).”