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Dissociating the Neural Substrates of Cranial and Limb Motor Impairment in an Ani

分离肛门中颅骨和肢体运动障碍的神经基质

基本信息

批准号：
8526447
负责人：
Emily Kate Plowman
金额：
$ 13.97万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-21 至 2015-06-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8526447
关键词：
Affect Animal Model Anus Aspiration Pneumonia Behavioral Bilateral Caregiver Burden Cause of Death Cephalic Corpus striatum structure Corticobulbar Tracts Corticospinal Tracts Deglutition Development Disease Dopamine Economic Burden Financial compensation Forelimb Functional disorder Goals Health Care Costs Human Impairment Individual Lead Lesion Limb structure Measures Mediating Morbidity - disease rate Motor Motor Cortex Movement Nature Operative Surgical Procedures Parkinson Disease Pathology Patients Population Quality of life Rehabilitation therapy Replacement Therapy Speech Symptoms System Testing Tongue Translating behavior test effective therapy improved indexing insight jaw movement microstimulation mortality motor deficit motor impairment neural circuit neuromechanism neurophysiology novel oral motor patient population relating to nervous system response treatment strategy

项目摘要

PROJECT SUMMARY Speech and swallowing impairments occur in 90% of individuals with Parkinson's Disease (PD) and aspiration pneumonia constitutes the leading cause of death in this patient population. While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions controlled by corticobulbar tracts such as speech and swallowing. This suggests that cranial motor and limb motor deficits are mediated by different underlying neural pathologies in PD, however the nature of these differences are not currently understood. The central goal of this proposal is to investigate differences in the neural mechanisms mediating corticobulbar versus corticospinal impairments in an animal model of PD. Using intracorticial microstimulation and a comprehensive behavioral testing battery consisting of both cranial motor and limb motor tasks, the proposed studies will (1) determine the differential effects of unilateral versus bilateral striatal dopamine depletion on cranial and limb motor function and corticobulbar and corticospinal circuits; (2) determine the differential responses of cranial and limb motor function in PD to targeted motor rehabilitation and dopamine replacement therapy; and (3) determine the differential effects of targeted motor rehabilitation and dopamine replacement therapy on the integrity of corticobulbar and corticospinal circuits. The results have the potential to guide the development of neurobiologically informed therapies that specifically target cranial motor impairment that can be translated to the human patient population. More effective treatment strategies of cranial motor dysfunction in PD will improve patient quality of life, reduce individual health care cost, aspiration pneumonia and ultimately morbidity in this disease population.

项目摘要 90%的帕金森病（PD）患者会出现语言和吞咽障碍，吸入性肺炎构成该患者群体的主要死亡原因。虽然目前的药物和手术干预可有效缓解PD的一般肢体运动症状，未能为皮质延髓束控制的颅运动功能提供显著的益处，说话和吞咽。这表明，颅运动和肢体运动缺陷是由不同的介导的， PD中的潜在神经病理学，然而这些差异的性质目前尚不清楚。的这项建议的中心目标是研究不同的神经机制介导皮质延髓与PD动物模型中的皮质脊髓损伤相比。使用皮质内微刺激和全面的行为测试电池包括颅运动和肢体运动任务，建议研究将（1）确定单侧与双侧纹状体多巴胺耗竭对颅和肢体运动功能以及皮质延髓和皮质脊髓回路;（2）确定鉴别帕金森病患者颅和肢体运动功能对靶向运动康复和多巴胺替代治疗的反应治疗;（3）确定有针对性的运动康复和多巴胺替代的差异效应皮质延髓和皮质脊髓回路完整性的治疗。这些结果有可能指导开发神经生物学信息疗法，专门针对颅运动障碍，转化为人类患者群体。颅运动功能障碍的有效治疗策略在PD中，将改善患者生活质量，降低个人医疗保健成本，吸入性肺炎，并最终这一疾病人群的发病率。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differential sensitivity of cranial and limb motor function to nigrostriatal dopamine depletion.

DOI：
10.1016/j.bbr.2012.09.031
发表时间：
2013-01-15
期刊：
BEHAVIOURAL BRAIN RESEARCH
影响因子：
2.7
作者：
Plowman, Emily K.;Maling, Nicholas;Rivera, Benjamin J.;Larson, Krista;Thomas, Nagheme J.;Fowler, Stephen C.;Manfredsson, Fredric P.;Shrivastav, Rahul;Kleim, Jeffrey A.
通讯作者：
Kleim, Jeffrey A.

Behavioral and neurophysiological correlates of striatal dopamine depletion: a rodent model of Parkinson's disease.

纹状体多巴胺耗竭的行为和神经生理学相关性：帕金森病的啮齿动物模型。