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Electrochemical assessment of behaviorally relevant circuit function after TBI

Electrochemical assessment of behaviorally relevant circuit function after TBI
TBI 后行为相关电路功能的电化学评估
批准号:
10296678
负责人:
Theresa Currier Thomas
金额:
$33.58万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-12-15 至 2023-11-30

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英文摘要
Project Summary/Abstract Traumatic brain injuries (TBI) frequently result in persisting post-traumatic neurological consequences, including hypersensitivity to light, with limited effective treatments. Vision is a primary sensory modality in humans, similar to whisker sensation in rodents. Primary sensory modalities incorporate a large portion of the brain for processing, making them susceptible to diffuse TBI. The goal of this proposal is to employ an experimental rodent model of diffuse TBI that highlights sensory deficits to evaluate delayed alterations in glutamate signaling as a universal consequence of TBI and its potential for modulation. Using this model in preliminary results the PI has demonstrated that TBI induces late-onset sensory hypersensitivity to whisker stimulation by post-injury day (PID) 28 that persists to PID 56. This injury-induced sensory hypersensitivity is measured using the established Whisker Nuisance Task (WNT), where whisker stimulation results in active evasion and aberrant responses in injured rats compared to ambivalence or curiosity in uninjured rats. Since the whisker circuit is glutamatergic, this research team implemented electrochemical microelectrode array technology, capable of real-time measurements of glutamate neurotransmission in vivo, for recordings within the relays of the whisker circuit in anesthetized rats. The PI reported that WNT scores positively correlate to the magnitude of potassium (KCl)-evoked glutamate release in the somatosensory thalamus and cortex. Evoked-glutamate release was sensitive to Ω-conotoxin, indicating hypersensitive presynaptic glutamate release as a potential mechanism for whisker hypersensitivity. Also, 3D reconstruction of neuron morphology shows increased numbers of terminating dendrites within the thalamus at PID 28, providing a potential source for increased glutamate release. KCl-evoked glutamate responses are required in anesthetized studies since whisker stimulation-evoked glutamate responses are suppressed by anesthesia. Thus, real-time recordings of glutamate neurotransmission in the awake, freely-moving rat permits the evaluation of whisker stimulation- evoked glutamate responses during the WNT. This has led to the central hypotheses that TBI-induced sensory hypersensitivity arises from altered glutamate signaling in sensory circuits and that early rehabilitation will restore circuit function and alleviate behavioral symptoms. To test these hypotheses adult male and female rats will be subjected to diffuse TBI by midline fluid percussion and evaluated for: 1) the influence of sex on late-onset sensory hypersensitivity to whisker stimulation and glutamate neurotransmission; 2) whisker stimulated-evoked glutamate release in awake, freely-moving rats, with respect to time post-diffuse TBI, and 3) evidence that circuit-directed rehabilitation, focused on the whiskers, can mitigate hypersensitive glutamate release and concurrent behavioral sensory hypersensitivity. Impact: Coupling this model of circuit disruption with electrochemical recordings in awake, freely-moving rats allows for evaluation of glutamate signaling as a biomarker for injury-induced persisting neurological deficits for evaluation of therapeutic approaches.
期刊论文(18)
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会议论文
Evidence for the induction of analgesic cross-tolerance between opioid and apelin/APJ systems in male rats.
在雄性大鼠中诱导阿片类药物和 apelin/APJ 系统之间镇痛交叉耐受的证据。
DOI: 10.15288/jsad.23-00377
发表时间: 2024
期刊: Journal of studies on alcohol and drugs
影响因子: 3.4
作者: [Abbasloo,Elham, Esmaeili-Mahani,Saeed, Kobeissy,Firas, Thomas,TheresaCurrier]
通讯作者: Thomas,TheresaCurrier
DOI: 10.3389/fneur.2020.00946
发表时间: 2020
期刊: Frontiers in neurology
影响因子: 3.4
作者: [Bromberg CE, Condon AM, Ridgway SW, Krishna G, Garcia-Filion PC, Adelson PD, Rowe RK, Thomas TC]
通讯作者: Thomas TC
Mild and Moderate Traumatic Brain Injury and Repeated Stress Affect Corticosterone in the Rat.
轻度和中度创伤性脑损伤和反复压力会影响大鼠的皮质酮。
DOI: 10.1089/neur.2020.0019
发表时间: 2020
期刊: Neurotrauma reports
影响因子: 2.4
作者: [Rowe RK, Ortiz JB, Thomas TC]
通讯作者: Thomas TC
DOI: 10.3389/fped.2022.937223
发表时间: 2022
期刊: FRONTIERS IN PEDIATRICS
影响因子: 2.6
作者: [Curry, Tala Maris, Esfandiarei, Mitra, Thomas, Theresa Currier, Rastogi, Reena Gogia]
通讯作者: Rastogi, Reena Gogia
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