A Focal Impact Model of Traumatic Brain Injury in Xenopus Tadpoles Reveals Behavioral Alterations, Neuroinflammation, and an Astroglial Response

Abstract

Traumatic Brain Injury (TBI) is a global driver of disability, and we currently lack effective therapies to promote neural repair and recovery. TBI is characterized by an initial insult, followed by a secondary injury cascade, including inflammation, excitotoxicity, and glial cellular response. This cascade incorporates molecular mechanisms that represent potential targets of therapeutic intervention. In this study, we investigate the response to focal impact injury to the optic tectum of Xenopus laevis tadpoles. This injury disrupts the blood-brain barrier, causing edema, and produces deficits in visually-driven behaviors which are resolved within one week. Within 3 h, injured brains show a dramatic transcriptional activation of inflammatory cytokines, upregulation of genes associated with inflammation, and recruitment of microglia to the injury site and surrounding tissue. Shortly afterward, astrocytes undergo morphological alterations and accumulate near the injury site, and these changes persist for at least 48 h following injury. Genes associated with astrocyte reactivity and neuroprotective functions also show elevated levels of expression following injury. Since our results demonstrate that the response to focal impact injury in Xenopus resembles the cellular alterations observed in rodents and other mammalian models, the Xenopus tadpole offers a new, scalable vertebrate model for TBI.

The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study

“…In conclusion, our results allow us to believe that our technique may represent a promising and dependable means of conducting a post-mortem diagnosis of TBI [42]. Moreover, the study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target to prevent the onset of secondary injuries and to improve the outcome of patients who have suffered from TBI, in terms of reducing neurological deficits [43][44][45][46][47].…”

Knockdown ofNeuroD2leads to seizure-like behaviour, brain neuronal hyperactivity and a leaky blood-brain barrier in aXenopus laevistadpole model of DEE75

“…NaF dye has been previously shown to be prevented from exciting the brain at stage 55 in uninjured tadpoles, indicating an intact BBB (D e jesus andino et al 2016). Adapting the method used in a recent study using X. laevis tadpoles to model traumatic brain injury (S pruiell eldridge et al 2022) for our younger tadpoles, we injected 9.2 nl of 0.1 mg/ml sodium fluorescein (NaF) into the 4th ventricle (Figure 4A) at stage 47. BBB permability was then measured by tracking dye distribution over 30 minutes (Figure 4B).…”

Brain implantation of tissue-level-soft bioelectronics via embryonic development

“…The copyright holder for this preprint (which this version posted June 2, 2024. ; https://doi.org/10.1101/2024.05. 29.596533 doi: bioRxiv preprint 4 Recent advances in flexible electronics [17][18][19][20][21] have yielded "tissue-like" mesh microelectronics: submicrometer-thick mesh electronics with tissue-level flexibility. Mesh microelectronics mimic the physicochemical properties of the extracellular matrix and are thus capable of seamlessly integrating into in vitro and in vivo neural tissues, forming gliosis-free bioelectronic interfaces and enabling long-term, stable, multichannel electrical recordings in 3D brain tissues at single-unit, single-spike spatiotemporal resolution over months 22 .…”

“…The copyright holder for this preprint (which this version posted June 2, 2024. ; https://doi.org/10.1101/2024.05. 29.596533 doi: bioRxiv preprint revealed that the presence of microelectronics had no discernible impact on embryo development or subsequent behaviors. Our device enables tissue-wide, continuous recording of neuron electrical activity at millisecond temporal resolution.…”

“…The copyright holder for this preprint (which this version posted June 2, 2024. ; https://doi.org/10.1101/2024.05. 29.596533 doi: bioRxiv preprint 6 We aimed to restrict device implantation to the cranial neural plate, as this region ultimately forms the brain (the caudal neural plate extends axially to form the spinal cord). According to our calculations, the formation of the frog embryo brain should introduce less than 30% axial strain to the device over the course of development.…”