Dorsal root injury and ischemic spinal cord injury

背根损伤和缺血性脊髓损伤

• 批准号: 10317545
• 负责人: YOUNG-JIN SON
• 金额: $ 43.59万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317545
• 关键词: Adult; Afferent Neurons; Animals; Area; Arteries; Astrocytes; Attention; Axon; Belief; Brachial plexus structure; Cauda Equina; Cells; Cervical; Child; Chronic; Data; Diagnosis; Disease; Dorsal; Ganglia; Glial Fibrillary Acidic Protein; Horns; Human; Image; Inbreeding; Incidence; Individual; Infarction; Inflammatory; Injury; Investigation; Ischemia; Label; Lead; Lesion; Lumbosacral plexus structure; Modeling; Mus; Muscle Spasticity; Natural regeneration; Neurologic Deficit; Neurons; Neurosurgical Procedures; Numbness; Obstruction; Oligodendroglia; Operative Surgical Procedures; Pain; Patients; Pattern; Peripheral; Peripheral Nerves; Plant Roots; Prognosis; Reporting; Rhizotomy procedure; Sensory; Severities; Spinal; Spinal Artery; Spinal Cord; Spinal Cord Ischemia; Spinal Ganglia; Spinal cord damage; Spinal cord injury; Spinal nerve root structure; Spinal nerve structure; Stroke; Testing; Thrombosis; Tissues; Traction; Trauma; Traumatic injury; Vascular blood supply; afferent nerve; axon injury; axon regeneration; axonal degeneration; clinically relevant; dorsal horn; effective therapy; experimental study; gray matter; improved; insight; male; mouse model; nerve damage; nerve injury; novel; relating to nervous system; restoration; spinal nerve posterior root; vascular inflammation

Abstract The dorsal root (DR) carries afferent axons of primary sensory neurons in the DR ganglion (DRG), which relay sensory information to second order neurons in the spinal cord. Traumatic injuries to DRs include brachial plexus, lumbosacral plexus and cauda equina injuries. Brachial plexus injury (BPI), the most common form of DR injury, results from high-energy traction damaging cervical DRs. These injuries evoke chronic, often agonizing, pain and permanent loss of sensation. We have no effective therapies that can reduce the extent of the initial injury or, at a later stage, restore sensory connections. It is therefore extremely important to understand the full extent of the damage caused by traumatic injuries to DRs, especially cervical DRs, and the mechanisms by which the damage occurs. DR injury directly damages primary sensory axons, resulting in sensory loss by permanently eliminating primary afferent axons in spinal cord. It is widely believed, however, that second order neurons in spinal cord remain intact. In contradiction to this belief, we have serendipitously found in mice that cervical DR crush can provoke profound neural tissue loss in spinal cord that is far more severe than previously thought. Notably, the incidence and magnitude of the neural tissue damage vary widely among mice, and interestingly increase in males and outbred mice and after avulsing DRs, a clinically relevant model of DR injury. We hypothesize that DR injury can cause severe spinal cord damage by eliciting intense spinal cord ischemia, when it damages large radicular arteries in mice with vulnerable arterial organization. Aim 1 will determine if the spinal cord damage is indeed ischemic by testing if photothrombotic occlusion of large radicular arteries in intact DRs is sufficient to elicit severe neural tissue loss in spinal cord. Aim 2 will determine if wide variability of arterial organization among mice determines the incidence and severity of spinal cord ischemia, thus critically impacting the pathophysiological progression of DR injuries. Current understanding is that spinal cord ischemia in humans is caused by direct damage to spinal cord, but not by remote trauma to spinal roots or peripheral nerve. The blood supply of the spinal cord in humans is also highly variable. Therefore, elucidation of this novel form of spinal cord ischemia and concurrent spinal cord damage, in mice, may ultimately provide new directions in the diagnosis, treatment and prognosis of both sporadic and surgical DR injuries.

抽象的 背根（DR）携带神经节（DRG）中主感觉神经元的传入轴突，该轴突继电器 感官信息到脊髓中的二阶神经元。 DRS的创伤性受伤包括臂 神经丛，腰椎神经丛和尾部。臂丛丛损伤（BPI），最常见的形式 DR损伤是由高能牵引力损害宫颈DRS引起的。这些伤害常常引起慢性 痛苦，疼痛和永久失去感觉。我们没有有效的疗法可以减少 最初的伤害或稍后阶段恢复感觉连接。因此，非常重要的是 了解由DRS造成的创伤伤害造成的损害的全部程度，尤其是宫颈DR，以及 损害发生的机制。 DR损伤直接损坏主感觉轴突，导致 通过永久消除脊髓中的初级传入轴突来丧失。但是，人们普遍认为 脊髓中的二阶神经元保持完整。与这种信念相矛盾，我们有偶然的 在小鼠中发现宫颈博士粉碎会引起脊髓中深层的神经组织丧失，这要多得多 比以前想象的严重。值得注意的是，神经组织损伤的发生率和大小差异很大 在小鼠中，有趣的是男性和近传小鼠的增加以及在脱离DRS之后，临床上相关的 DR损伤的模型。我们假设DR受伤会通过激烈而引起严重的脊髓损伤 脊髓缺血，当它损害脆弱的动脉组织的小鼠中的大辐射动脉时。 AIM 1将通过测试光胞栓性闭塞是否确实是缺血性的，确定脊髓损伤是否确实是缺血的 完整的DR中的大辐射动脉足以引起脊髓中严重的神经组织丧失。 AIM 2意志 确定小鼠中动脉组织的广泛变异性是否确定脊柱的发病率和严重程度 绳索缺血，因此严重影响了DR损伤的病理生理进展。当前的 了解人类的脊髓缺血是由对脊髓的直接损害引起的，但不是由 远程创伤到脊髓或周围神经。人类脊髓的血液供应也很高 多变的。因此，阐明这种新型的脊髓缺血形式和并发脊髓损伤， 在小鼠中，最终可能提供零星和预后的新方向 外科医生受伤。