Instrument for Intracerebral Microinjections and Electrophysiology

脑内显微注射和电生理学仪器

基本信息

  • 批准号:
    7538429
  • 负责人:
  • 金额:
    $ 19.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-09-30 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Among the most devastating diseases are those of the central nervous system (CNS). Profoundly disabling and chronic, they wreak emotional, physical, and economic havoc upon individuals, their families, and society. In the 2000 report by the Family Caregiver Alliance (www.caregiver.org), 1.1 million new cases of the 10 most common brain diseases were diagnosed in the U.S. alone. More than 16 million patients receive ongoing care for these diseases, many of whom might still benefit from more effective therapeutic modalities. Among the most promising interventions is "restorative neurosurgery." Traditionally, neurosurgical intervention has involved removal of pathological tissues. In restorative neurosurgery, however, therapeutic agents or tissues are introduced within distinct regions of the CNS using a minimally-invasive stereotactic surgical procedure. Restorative therapeutics include trophic factors, gene therapy vectors, chemo-therapeutics, therapeutic cells (neural transplantation), or other neuroactive compounds. Optimizing the benefits of restorative therapeutics will depend on a neurosurgeon's ability to deliver these medicines with exquisite accuracy and minimal damage to functionally normal tissue. Stereotactic surgery allows procedures to be performed on structures deep within the brain with reduced, but not negligible, damage to tissue above and surrounding the target structure. Stereotactic injection of therapeutic cells, for example, holds promise as a method for reconstituting cell populations, supplementing levels of locally produced brain chemicals, and re-establishing neural circuitry. One focus of the original SBIR grant application was to address the shortcomings in the methodology and instrumentation used for neural transplantation. Despite some successes, functional recovery following brain cell injections has been modest and highly variable to date. Marginal patient recovery has been directly associated with the implanted cells' poor survival rate; increasing the success of neural cell engraftment would substantially advance the utility of this potentially powerful therapeutic approach. Animal studies have demonstrated that transplanted cell survival rates increase when the injection instrument used to deliver cells into the brain is smaller and the injection volume reduced. "Microvolumes" of cells (0.25 2 5L) delivered through a pulled glass micropipette with a final diameter of approximately 70 microns have a survival rate 250% or greater higher than larger cell volumes (5-20 5L) injected through a 0.5 mm-diameter cannula. Commonly used injectors for human surgery are 0.5-1 mm in diameter, and graft volume is typically 10-20 5L. SBIR funding has enabled the development of an Intracerebral Microinjection Instrument (IMI) that permits precise micro-volumes of therapeutic agent to be stereotacticly placed in a three-dimensional array within the human brain using a single penetration of overlying tissue by a "guide" cannula. The IMI delivery cannula is extremely small, ranging from 20 to 200 micrometers in diameter. It is capable of electrophysiological recording before, during, and after delivery of the therapeutic, permitting exquisite targeting precision. In addition to neural transplantation, the IMI is particularly well-suited for direct delivery of a variety of agents, including those used for chemotherapy. Indeed, neurosurgical treatment for glioblastoma multiforme, an aggressively malignant and deadly carcinoma, may be a primary indication for the IMI. This proposal is for improvements to this instrument, preparing it for use in neurosurgical approaches for human diseases of the CNS, and to obtain funding for the FDA market clearance of the technology. PUBLIC HEALTH RELEVANCE: An emerging area of neurosurgical treatment of brain disease involves inserting chemotherapeutics, cells, antioxidants, or other therapeutic agents directly into brain in order to bypass the blood/brain barrier, and in order to achieve concentration at a precise anatomical site in brain. The Intracerebral Microinjection Instrument proposed herein improves the ability to make such injections with minimal damage to the brain, and with minimal activation of the brains rejection mechanisms for foreign material.
描述(由申请人提供):其中最具破坏性的疾病是中枢神经系统(CNS)的疾病。严重致残和慢性,它们对个人、家庭和社会造成情感、身体和经济上的破坏。在2000年家庭护理者联盟(www.caregiver.org)的报告中,仅在美国就有110万例新的10种最常见的脑部疾病。超过1600万患者接受这些疾病的持续护理,其中许多人可能仍然受益于更有效的治疗方式。其中最有前途的干预措施是“恢复性神经外科”。“传统上,神经外科干预涉及切除病理组织。然而,在恢复性神经外科中,使用微创立体定向外科手术将治疗剂或组织引入CNS的不同区域内。恢复性治疗剂包括营养因子、基因治疗载体、化学治疗剂、治疗性细胞(神经移植)或其他神经活性化合物。优化恢复性治疗的益处将取决于神经外科医生以精确的准确性和对功能正常组织的最小损伤提供这些药物的能力。立体定向手术允许在脑内深处的结构上进行手术,对目标结构上方和周围的组织的损伤减少但不可忽略。例如,治疗性细胞的立体定向注射有望成为一种重建细胞群、补充局部产生的脑化学物质水平和重建神经回路的方法。最初SBIR拨款申请的一个重点是解决用于神经移植的方法和仪器的缺点。尽管取得了一些成功,但脑细胞注射后的功能恢复迄今为止一直是适度的,并且变化很大。边缘患者恢复与植入细胞的低存活率直接相关;增加神经细胞移植的成功率将大大提高这种潜在的强大治疗方法的实用性。动物研究表明,当用于将细胞输送到大脑中的注射仪器较小并且注射体积减少时,移植细胞存活率增加。细胞的“微体积”(0.25 通过最终直径约为70微米的拉伸玻璃微量移液管递送的细胞体积(5-20 μ L)的存活率比通过0.5 mm直径套管注射的较大细胞体积(5-20 μ L)高250%或更高。用于人体外科手术的常用注射器直径为0.5-1 mm,移植物体积通常为10-20 5L。SBIR的资助使得能够开发脑内显微注射仪器(IMI),其允许通过“引导”套管使用覆盖组织的单次穿透将精确的微体积的治疗剂立体定向地放置在人脑内的三维阵列中。IMI输送套管非常小,直径范围为20至200微米。它能够在治疗剂递送之前、期间和之后进行电生理记录,从而允许精确的靶向。除了神经移植,IMI特别适合于直接递送各种药剂,包括用于化疗的药剂。的确,神经外科治疗多形性胶质母细胞瘤(一种侵袭性恶性和致命的癌症)可能是IMI的主要适应症。该提案旨在改进该仪器,使其准备用于治疗人类CNS疾病的神经外科方法,并为该技术的FDA市场许可获得资金。 公共卫生相关性:脑疾病的神经外科治疗的新兴领域涉及将化学治疗剂、细胞、抗氧化剂或其他治疗剂直接插入脑中,以绕过血/脑屏障,并在脑中的精确解剖部位实现浓度。本文提出的脑内显微注射仪器提高了进行这种注射的能力,对大脑的损伤最小,并且对外来物质的大脑排斥机制的激活最小。

项目成果

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LEE D MARGOLIN其他文献

LEE D MARGOLIN的其他文献

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{{ truncateString('LEE D MARGOLIN', 18)}}的其他基金

Software Guided Localization of the Subthalamic Nucleus During DBS Surgeries
DBS 手术期间软件引导的丘脑底核定位
  • 批准号:
    7749485
  • 财政年份:
    2009
  • 资助金额:
    $ 19.65万
  • 项目类别:
Polymodal Electrode System for Intracranial Applications
用于颅内应用的多模态电极系统
  • 批准号:
    6549975
  • 财政年份:
    2002
  • 资助金额:
    $ 19.65万
  • 项目类别:
Instrument for Intracerebral Microinjections and Electrophysiology
脑内显微注射和电生理学仪器
  • 批准号:
    7684046
  • 财政年份:
    1998
  • 资助金额:
    $ 19.65万
  • 项目类别:
TRIMODAL ELECTRODE SYSTEM FOR PALLIDOTOMY & THALAMOTOMY
用于苍白球切开术的三峰电极系统
  • 批准号:
    2892347
  • 财政年份:
    1997
  • 资助金额:
    $ 19.65万
  • 项目类别:
TRIMODAL ELECTRODE SYSTEM FOR PALLIDOTOMY & THALAMOTOMY
用于苍白球切开术的三峰电极系统
  • 批准号:
    2649572
  • 财政年份:
    1997
  • 资助金额:
    $ 19.65万
  • 项目类别:
TRIMODAL ELECTRODE SYSTEM FOR PALLIDOTOMY & THALAMOTOMY
用于苍白球切开术的三峰电极系统
  • 批准号:
    2422044
  • 财政年份:
    1997
  • 资助金额:
    $ 19.65万
  • 项目类别:
GROWTH-ASSOSCIATED PROTEINS
生长相关蛋白
  • 批准号:
    3504676
  • 财政年份:
    1992
  • 资助金额:
    $ 19.65万
  • 项目类别:

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