• Author
    De'Larrian Knight
  • Discovery PI

    Dr. Mayumi Prins

  • Project Co-Author

    Sydney Bennett

  • Abstract Title

    Decompressive Hemicraniectomy exacerbates Cerebellar Glymphatic Dysfunction in Adolescent Rats exposed to Severe Traumatic Brain Injury

  • Discovery AOC Petal or Dual Degree Program

    Basic, Clinical, & Translational Research

  • Abstract

    Severe traumatic brain injury (TBI) is a leading cause of death among adolescents, with limited options for acute care. Given the complexity of the neuropathology affecting the central nervous system after TBI, therapeutic interventions are guided by understanding the underlying processes. One of the most effective forms of treatment for severe TBI, decompressive hemicraniectomy (DHC), involves removing a piece of the skull to relieve pressure on the brain. The recently discovered glymphatic system describes a brain-wide network of perivascular cerebrospinal fluid (CSF) channels that promotes CSF-interstitial fluid exchange during sleep, cleansing the brain of metabolic waste products. Anterograde CSF movement through this system is partially dependent on the pulsatility of the brain against the closed cranial vault, which is lost following DHC. Few studies examine the impact of TBI and subsequent DHC on the glymphatic system in adolescents, and there is little evidence describing the role of cerebellar glymphatic flow in TBI neuropathology. We believe that severe TBI attenuates cerebellar glymphatic flow, which DHC further exacerbates. We subjected adolescent rats (40 PND) to a severe closed cortical impact injury (2.5 mm) in the left hemisphere. Intracisternal CSF tracer was injected into the cisterna magna to measure glymphatic flow. Three treatment groups were used in this study: SHAM (craniotomy without TBI), 5-day post-injury, and 10-day post-injury. The experimental groups were then further divided into TBI + craniotomy and TBI + hemicraniectomy groups. For tissue collection, 100-micrometer cerebellum slices were mounted for confocal microscopy to measure mean fluorescence. 40-micrometer cerebellum slices were stored for immunohistochemistry of Aquaporin-4, GFAP, and endothelial markers. The results of this study could give further insight into the role of cerebellar glymphatic disruption in severe TBI neuropathology and could provide evidence for more accurate prognostic assessment of severe TBI in clinical settings.