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.

摘要 背根（DR）携带DR神经节（DRG）中初级感觉神经元的传入轴突， 感觉信息传递到脊髓中的二级神经元。DR的创伤性损伤包括肱动脉 神经丛、腰骶神经丛和马尾神经损伤。臂丛神经损伤（BPI），最常见的形式， DR损伤，由高能量牵引损伤颈椎DR引起。这些损伤引起慢性， 痛苦，疼痛和永久性的感觉丧失。我们没有有效的治疗方法可以减少 最初的损伤，或在后期恢复感觉连接。因此，极其重要的是， 了解创伤性损伤对DR，特别是颈部DR造成的损伤的全部程度， 造成损害的机制。DR损伤直接损伤初级感觉轴突，导致 永久性地消除脊髓中的初级传入轴突导致感觉丧失。然而，人们普遍认为， 脊髓中的二级神经元保持完整。与此相反，我们偶然发现， 在小鼠中发现，颈部DR挤压可引起脊髓中严重的神经组织损失， 比以前想象的要严重。值得注意的是，神经组织损伤的发生率和程度变化很大 有趣的是，在雄性和远交系小鼠中， DR损伤模型。我们假设DR损伤可以通过引发强烈的脊髓损伤， 脊髓缺血，当它损害动脉组织脆弱的小鼠的大根动脉时。 目的1将通过检测脊髓损伤是否为缺血性， 完整DR中的大根动脉足以引起脊髓中严重的神经组织损失。目标2将 确定小鼠中动脉组织的广泛变异性是否决定了脊髓损伤的发生率和严重程度， 脊髓缺血，从而严重影响DR损伤的病理生理学进展。电流 目前的理解是，人类的脊髓缺血是由脊髓的直接损伤引起的，而不是由 脊髓根或周围神经的远程创伤。人类脊髓的血液供应也是非常高的。 变量因此，阐明这种新形式的脊髓缺血和并发的脊髓损伤， 在小鼠中，可能最终为散发性和 手术DR损伤。