Kelso Matthew L, Gendelman Howard E
Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6045.
Curr Pharm Des. 2014;20(26):4284-98.
The pathophysiology of degenerative, infectious, inflammatory and traumatic diseases of the central nervous system includes a significant immune component. As to the latter, damage to the cerebral vasculature and neural cell bodies, caused by traumatic brain injury (TBI) activates innate immunity with concomitant infiltration of immunocytes into the damaged nervous system. This leads to proinflammatory cytokine and prostaglandin production and lost synaptic integrity and more generalized neurotoxicity. Engagement of adaptive immune responses follows including the production of antibodies and lymphocyte proliferation. These affect the tempo of disease along with tissue repair and as such provide a number of potential targets for pharmacological treatments for TBI. However, despite a large body of research, no such treatment intervention is currently available. In this review we will discuss the immune response initiated following brain injuries, drawing on knowledge gained from a broad array of experimental and clinical studies. Our discussion seeks to address potential therapeutic targets and propose ways in which the immune system can be controlled to promote neuroprotection.
中枢神经系统退行性、感染性、炎症性和创伤性疾病的病理生理学包括重要的免疫成分。就后者而言,创伤性脑损伤(TBI)导致的脑血管和神经细胞体损伤会激活先天免疫,同时免疫细胞浸润到受损的神经系统中。这会导致促炎细胞因子和前列腺素的产生,以及突触完整性丧失和更广泛的神经毒性。随后会引发适应性免疫反应,包括抗体产生和淋巴细胞增殖。这些会影响疾病的进程以及组织修复,因此为TBI的药物治疗提供了许多潜在靶点。然而,尽管进行了大量研究,但目前尚无此类治疗干预措施。在本综述中,我们将借鉴从广泛的实验和临床研究中获得的知识,讨论脑损伤后引发的免疫反应。我们的讨论旨在探讨潜在的治疗靶点,并提出控制免疫系统以促进神经保护的方法。