Research Career Scientist for Naren Banik, PhD

目前的研究活动集中在脊髓损伤(SCI)、帕金森病(PD)和多发性 硬化症(MS)。脊髓损伤是一种复杂的衰弱疾病，会导致终生的神经和骨骼缺陷。 由于不能动弹而造成的肌肉萎缩和丢失。我们的实验室是最早证明雌激素(E2)驱动 对实验性脊髓损伤大鼠的神经保护作用，提示E2可作为神经创伤的临床评估依据。新的 包括纳米颗粒在内的智能药物输送技术可能会提高药物安全性并改善 功效。因此，我们的目标是检查一种新型的缓释载药纳米颗粒(SNP-E2)凝胶的效果 大鼠脊髓损伤模型中神经元功能障碍和骨骼肌丢失的补丁。我们假设焦点投放 通过缓释纳米粒释放雌激素SNP-E2将维持较低的全身E2水平(血浆)和更高的水平 组织浓度，从而允许最大限度地从神经和骨骼恢复治疗潜力 脊髓损伤中的肌肉损失。为了检验这一假设，提出了两个具体目标：(目标1)检查 新的缓释SNP-E2并测定其动力学、生物分布、毒性和在中、低剂量下的作用 SNP-E_2对中、重度脊髓损伤后骨骼肌损伤的影响 严重的脊髓损伤。总体而言，拟议的研究应提供一种安全和新颖的战略，以改善健康和 脊髓损伤退伍军人的功能恢复。 帕金森氏病(PD)是一种进行性退行性疾病，影响着近8万退伍军人。而当 这种退变过程的机制仍然不清楚，可能涉及慢性炎症。钙调蛋白 它不仅在大脑(SN-DA神经元)和脊髓(SC)退行性变中起着关键作用，它还可能推动 炎症和疾病进展。抑制钙蛋白水解酶可减弱T细胞亚群 MPTP小鼠，提示Calain参与了炎症过程。我们的目标是开发出治疗方法 用阻断炎症过程、保护神经元、控制疾病的药物治疗帕金森病的策略 进步，改善功能。我们假设，钙蛋白酶的激活，炎性T细胞的渗透 (Th1/Th17)，以及释放的细胞因子和趋化因子参与了帕金森病和钙蛋白酶的进行性退变 抑制剂治疗可以减少退化，减缓疾病进展，并改善功能。两个具体目标 我将检验假设：(目标1)研究Calain调节和T细胞渗透在SC退变中的作用 和MPTP小鼠的疾病进展，表征浸润性T细胞，评估细胞因子/趋化因子水平 血清，并测定SC的细胞死亡参数和钙蛋白激活；(目的2)检查治疗是否 应用钙蛋白酶抑制剂的MPTP小鼠将减少退行性炎症事件，改善功能。 在多发性硬化症及其动物模型中也发现了钙蛋白酶活性的增加[实验性自身免疫 疾病(EAE)]，Calain参与T细胞(Th1/Th17)的激活，轴突/髓鞘的降解，以及 T细胞趋化性。在多发性硬化患者的脑和脊髓中钙蛋白被激活的同时， Calain的两个亚型，calain-1和calain-2，仍未确定。我们假设DISTINCT的激活 钙蛋白酶亚型可能有利于MS患者炎症介质和Th1/Th17细胞的扩张，这可能 可通过抑制钙蛋白酶而减弱。研究包括(AIM 1)检测多发性硬化症患者样本以确定 两种主要的钙蛋白酶亚型参与了免疫细胞类型的失调，影响了 以及(目标2)研究一种不同的钙蛋白酶亚型是否与疾病的进展有关，影响- 研究MS的神经退变过程所获得的数据将揭示Calain抑制剂对抑制的影响 特定的钙蛋白酶和减弱疾病的免疫和神经退行性手臂的发育 治疗多发性硬化和其他神经退行性疾病的新疗法。这些研究项目的总体目标是 就是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。

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.