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Repetitive mild traumatic brain injury induces ventriculomegaly and cortical thinning in juvenile rats

Description
Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries…

Traumatic brain injury (TBI) most frequently occurs in pediatric patients and remains a leading cause of childhood death and disability. Mild TBI (mTBI) accounts for 70-90% of all TBI cases, yet its neuropathophysiology is still poorly understood. While a single mTBI injury can lead to persistent deficits, repeat injuries increase the severity and duration of both acute symptoms and long term deficits. In this study, to model pediatric repetitive mTBI (rmTBI) we subjected unrestrained juvenile animals (post-natal day 20) to repeat weight drop impact. Animals were anesthetized and subjected to sham or rmTBI once per day for 5 days. At 14 days post injury (PID), magnetic resonance imaging (MRI) revealed that rmTBI animals displayed marked cortical atrophy and ventriculomegaly. Specifically, the thickness of the cortex was reduced up to 46% beneath and the ventricles increased up to 970% beneath the impact zone. Immunostaining with the neuron specific marker NeuN revealed an overall loss of neurons within the motor cortex but no change in neuronal density. Examination of intrinsic and synaptic properties of layer II/III pyramidal neurons revealed no significant difference between sham and rmTBI animals at rest or under convulsant challenge with the potassium channel blocker, 4-Aminophyridine. Overall, our findings indicate that the neuropathological changes reported after pediatric rmTBI can be effectively modeled by repeat weight drop in juvenile animals. Developing a better understanding of how rmTBI alters the pediatric brain may help improve patient care and direct "return to game" decision making in adolescents.
ContributorsGoddeyne, Corey (Author) / Anderson, Trent (Thesis advisor) / Smith, Brian (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
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Automated Fluorescence-Guided Navigation for Patch-Clamp Electrophysiology

Description
Patch-clamp electrophysiology is the current gold-standard technique for obtaining high-resolution recordings of neuronal activity in vivo. However, robotic technologies recently developed to automate these labor-intensive and low-throughput experiments are limited to superficial regions of the brain or lack cell type specific-targeting (Kodandaramaiah et al., 2012; Suk et al., 2017; Annecchino…

Patch-clamp electrophysiology is the current gold-standard technique for obtaining high-resolution recordings of neuronal activity in vivo. However, robotic technologies recently developed to automate these labor-intensive and low-throughput experiments are limited to superficial regions of the brain or lack cell type specific-targeting (Kodandaramaiah et al., 2012; Suk et al., 2017; Annecchino et al., 2017) . In this work, a new approach for automatically navigating patch-clamp micropipette electrodes using fluorescence feedback collected at the electrode aperture was developed and validated in vitro. In future efforts, an internal excitation source will be integrated into the system to enable micropipette navigation at any electrode-accessible depth and the system will be tested in vivo using fluorescence feedback from cell type-specific labels.
ContributorsHowell, Madeleine R. (Author) / Smith, Barbara (Thesis director) / Anderson, Trent (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05