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The Role of Homotopic Functional Connectivity in Cortical Remapping after Focal Ischemia

同位功能连接在局灶性缺血后皮质重映射中的作用

基本信息

批准号：
9275050
负责人：
Andrew Wiggen Kraft
金额：
$ 2.8万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9275050
关键词：
Acute Address Animal Model Appearance Attention Behavioral Bilateral Brain Characteristics Communication Conflict (Psychology)Contralateral Equilibrium Event Evolution Functional Imaging Genetic Grant Human I/LnJ Mouse Image Impairment Incidence Individual Infarction Injury Ischemia Ischemic Stroke Lead Lesion Location Maps Measures Modality Modeling Molecular Molecular Profiling Motor Mouse Strains Mus Neuronal Plasticity Optics Pathway Analysis Patients Pattern Performance Physiology Rattus Recovery Recovery of Function Reporting Research Personnel Research Project Grants Rest Role Sensorimotor functions Signal Transduction Somatosensory Cortex Stroke Survivors System Testing Time Work axonal sprouting brain tissue cortex mapping disability experience imaging capabilities imaging modality improved interest loss of function minimally invasive mouse model network architecture neural patterning neurotransmission novel programs public health relevance repaired repetitive transcranial magnetic stimulation restoration sensory cortex somatosensory stroke survivor stroke therapy synaptogenesis targeted treatment

项目摘要

DESCRIPTION (provided by applicant): Stroke is the leading cause of disability in the US, with an annual incidence of 780,000 and over 5.8 million survivors. Most stroke survivors experience a limited degree of spontaneous recovery in the first weeks to months following injury, but this recovery is often incomplete. For decades animal models have implicated cellular and molecular events including synaptogenesis, dendritic and axonal sprouting, as being important for recovery. While it was believed that these cellular programs are involved in the formation of new connections important for recovery, more recent systems-level analysis have revealed how brain-network plasticity may be involved in recovery. Focal ischemia results in the acute loss of function to modalities mapped onto infarcted brain tissue. Interestingly, behavioral recovery occurs as lost modalities remap onto the peri-infarct cortex suggesting remapping may be critical for behavioral recovery. In addition to examining local peri-lesional changes, more recent work has examined alterations in global brain networks following stroke. By examining patterns of neural synchronization in the "resting state" brain, termed functional connectivity (fc, it is clear that global patterns of functional connectivity are altered following focal ischemia. Immediately following ischemic stroke, weak interhemispheric homotopic fc (which is robust in healthy individuals) predicted poor motor and attentional performance in humans. In a rat focal ischemia recovery model, interhemspheric homotopic fc decreased following injury and recovered in parallel with sensorimotor behavioral performance. These studies suggest that remapping may involve long range network changes. Indeed, molecular profiling has revealed synaptogenesis and neuroplasticity occurring in the contralesional cortex after injury. However, the role the contralesional influence on remapping and recovery is not well defined. There is some evidence that homotopic interhemispheric fc may reflect the excitatory/inhibitory balance between homoptic cortical regions and that this balance is important for normal unilateral functionality 15. Ischemic injury is thought to disrupt network architecture and result in increase inhibitory tone in the perilesional cortex that exacerbates deficits and limits recovery. This coul explain the potential efficacy of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to restore interhemispheric balance and improve sensorimotor function. However, there are conflicting reports in humans and animal models regarding the impact of contralateral homotopic influence on functional recovery, and it is unclear if interhemispheric communication benefits or inhibits recovery. Animal models may enable a better understanding of contralesional cortex physiology after ischemia allowing better targeting of therapies for stroke patients. In this grant, I will test the hypothesis that interhemispheric functional connectivity directly influences cortical remapping and behavioral recovery after focal ischemia. To visualize cortical maps and fc in a mouse focal ischemia model, I will utilize imaging modalitiy, fc optical intrinsic signal (fcOIS) to address the followig aims: Aim 1: To determine the relationship between interhemispehric fc, cortical remapping, and behavioral recovery following focal ischemia in mice. Aim 2: To determine the influence of transcallosal interhemispheric connectivity on cortical remapping and behavioral recovery following focal ischemia.