Research Career Scientist for Naren Banik, PhD

目前的研究活动主要集中在脊髓损伤（SCI），帕金森病（PD）和多发性硬化症（MS）。 硬化症（MS）。SCI是一种复杂的使人衰弱的疾病，导致终生的神经功能缺损以及骨骼损伤。 由于不动而导致的损失和肌肉萎缩。我们的实验室是最早证明雌激素（E2）驱动 在大鼠实验性SCI中的神经保护作用，表明E2值得在神经创伤中进行临床评价。新 包括纳米颗粒在内的智能药物递送技术可以提高药物安全性， 功效因此，我们的目标是研究一种新型的缓释E2-负载纳米粒子（SNP-E2）凝胶的作用 贴剂对SCI大鼠模型中神经元功能障碍和骨骼肌损失的作用。我们假设局部给药 通过缓释纳米颗粒SNP-E2释放雌激素将维持低的全身E2水平（血浆）和更高的 组织浓度，从而允许最大化的治疗潜力，从神经和骨骼 脊髓损伤的肌肉损失。为了检验这一假设，提出了两个具体的目标：（目标1）检查一个 新的缓释SNP-E2，并确定其动力学，生物分布，毒性，以及在中度和 （目的2）确定SNP-E2对中度和重度SCI患者骨骼肌损失变化的影响， 严重SCI。总的来说，拟议的研究应该提供一种安全和新颖的策略，以改善健康， 脊髓损伤退伍军人的功能恢复 帕金森病（PD）是一种渐进性退行性疾病，影响近80，000名退伍军人。而 这种变性过程的机制仍然难以捉摸，可能涉及慢性炎症。calpain 不仅在脑（SN-DA神经元）和脊髓（SC）变性中起关键作用， 炎症和疾病进展。钙蛋白酶的抑制减弱了T细胞的一个独特的亚群， MPTP小鼠，表明钙蛋白酶参与炎症过程。我们的目标是开发治疗 用阻断炎症过程、保护神经元、控制疾病的药物治疗PD的策略 进步，改善功能。我们假设钙蛋白酶激活，炎症T细胞浸润 (Th1/Th17），释放的细胞因子和趋化因子参与PD的进行性变性，钙蛋白酶 抑制剂治疗可以减少变性、减缓疾病进展和改善功能。两个具体目标 目的1）探讨钙蛋白酶调节和T细胞浸润在SC退变中的作用 和疾病进展，表征浸润性T细胞，评估MPTP小鼠中的细胞因子/趋化因子水平， 血清，并确定SC中的细胞死亡参数和钙蛋白酶激活;（目的2）检查是否治疗 具有钙蛋白酶抑制剂的MPTP小鼠将减少退行性炎症事件并改善功能。 钙蛋白酶活性增加也被发现在MS以及在其动物模型[实验性自身免疫性 疾病（EAE）]，并且钙蛋白酶涉及T细胞（Th1/Th17）的活化、轴突/髓磷脂的降解，以及 T细胞趋化性。虽然钙蛋白酶在MS患者的大脑和脊髓中被激活，但 两种钙蛋白酶同种型钙蛋白酶-1和钙蛋白酶-2仍不明确。我们假设，不同的激活 钙蛋白酶亚型可能有利于MS患者炎症介质和Th1/Th17细胞的扩增，这可能 通过钙蛋白酶抑制而减弱。研究包括（目的1）测试MS患者样本，以确定 两种主要的钙蛋白酶同种型参与免疫细胞类型的失调，影响免疫细胞的免疫臂。 疾病;和（目的2）调查是否一个独特的钙蛋白酶亚型与疾病进展，影响， 所获得的数据将揭示钙蛋白酶抑制剂对抑制MS的作用。 特异性钙蛋白酶和衰减的免疫和神经退行性武器的疾病， 用于治疗MS和其它神经变性疾病的新疗法。这些研究项目的总体目标 最大限度地减少退化，最大限度地发挥功能，改善退伍军人的健康状况。

Current research activities are focused on Spinal Cord Injury (SCI), Parkinson’s Disease (PD), and Multiple Sclerosis (MS). SCI is a complex debilitating condition leading to life-long neurological deficits as well as bone loss and muscle atrophy due to immobility. Our laboratory was among the first to show that estrogen (E2) drives neuroprotection in experimental SCI in rats, suggesting E2 warrants clinical evaluation in neurotrauma. New smart drug delivery techniques, including nanoparticles, may allow for increased drug safety and improved efficacy. Thus, the goal is to examine the effects of a novel slow release E2-loaded nanoparticle (SNP-E2) gel patch on neuronal dysfunction and skeletal muscle loss in a rat model of SCI. We hypothesize that focal delivery of estrogen via slow release nanoparticles SNP-E2 will maintain low systemic E2 levels (plasma) and higher tissue concentrations, thereby allowing for maximized therapeutic potential for recovery from neural and skeletal muscle loss in SCI. To test the hypothesis, two specific aims are proposed: (Aim 1) Examine the delivery of a novel slow release SNP-E2 and determine its kinetics, bio-distribution, toxicity, and effects in moderate and severe SCI and (Aim 2) Determine the effects of SNP-E2 on alterations of skeletal muscle loss in moderate and severe SCI. Overall, the proposed studies should provide a safe and novel strategy to improve health and functional recovery for Veterans with SCI. Parkinson’s disease (PD) is a progressive degenerative disorder affecting almost 80,000 Veterans. While the mechanisms of this degenerative process remain elusive, chronic inflammation may be involved. Calpain not only plays a pivotal role in brain (SN-DA neurons) and spinal cord (SC) degeneration, it may also drive inflammation and disease progression. Inhibition of calpain attenuates a distinct subpopulation of T cells in MPTP mice, suggesting calpain’s involvement in the inflammatory process. Our goal is to develop therapeutic strategies to treat PD with agents that block the inflammatory process, protect neurons, control disease progression, and improve function. We hypothesize that calpain activation, infiltration of inflammatory T cells (Th1/Th17), and released cytokines and chemokines are involved in progressive degeneration of PD, and calpain inhibitor treatment may reduce degeneration, slow disease progression, and improve function. Two specific aims will test the hypothesis: (Aim 1) Investigate the role of calpain regulation and T cell infiltration in SC degeneration and disease progression in MPTP mice, characterize infiltrating T cells, assess cytokine/chemokine levels in sera, and determine cell death parameters and calpain activation in SC; (Aim 2) Examine whether treatment of MPTP mice with calpain inhibitor will reduce degenerative inflammatory events and improve function. Increased calpain activity has also been found in MS as well as in its animal model [experimental autoimmune disease (EAE)], and calpain is implicated in the activation of T cells (Th1/Th17), degradation of axon/myelin, and T cell chemotaxis. While calpain is activated in brain and spinal cord of MS patients, the precise involvement of the two calpain isoforms, calpain-1 and calpain-2, remains undefined. We hypothesize that activation of distinct calpain isoform may favor expansion of inflammatory mediators and Th1/Th17 cells in MS patients, which could be attenuated by calpain inhibition. Studies include (Aim 1) testing MS patient samples to determine which of the two major calpain isoforms is involved in dysregulation of immune cell types, influencing immune arms of the disease; and (Aim 2) Investigating whether a distinct calpain isoform is linked with disease progression, influ- encing the neurodegenerative process in MS. Data obtained will reveal the effect of calpain inhibitor on inhibition of specific calpains and attenuation of both immune and neurodegenerative arms of the disease for developing novel therapy for treating MS and other neurodegenerative diseases. The overall goal of these research projects is to minimize degeneration and maximize function and improve the health of our Veterans.