Vawter M P, Dillon-Carter O, Tourtellotte W W, Carvey P, Freed W J
Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeths, Washington, DC 20032, USA.
Exp Neurol. 1996 Dec;142(2):313-22. doi: 10.1006/exnr.1996.0200.
Transforming growth factor (TGF)beta plays a role in injury repair in sites surrounding brain injury. The present study tested the hypothesis that TGFbeta1 and TGFbeta2 levels in the postmortem CSF of patients with neurodegenerative disorders would be elevated compared to those in normal subjects. Free TGFbeta1 and total TGFbeta2 were measured by ELISA in postmortem ventricular cerebrospinal fluid (vCSF) of patients with Parkinson's disease (n = 30), Alzheimer's disease (n = 30), multiple sclerosis (n = 15), and schizophrenia (n = 12) and of normal controls (n = 16). In addition, albumin, IgG, and total protein in vCSF were measured. Both TGFbeta1 and TGFbeta2 were significantly different between groups (P < 0.002 and P < 0.001, respectively). Parkinson's disease vCSF showed significant increases in both TGFbeta1 (P = 0.015) and TGFbeta2 (P = 0.012) compared to normal controls. There was a trend for TGFbeta2 to be elevated in Alzheimer's disease and multiple sclerosis vCSFs, which failed to achieve significance. There were no differences between controls and schizophrenics in TGFbeta1 or TGFbeta2. Alzheimer's disease vCSF showed a significant decrease in protein compared to all other groups, which was not related to blood-brain barrier permeability, age, or autolysis differences. Evidence is presented suggesting that some TGFbeta1 may leak into the vCSF from plasma. Autopsy vCSF levels of TGFbeta isoforms were found to be distinctly different from those reported for human serum, especially for TGFbeta2, which is undetectable in plasma. These results indicate that further in vivo studies of TGFbeta2 in the CSF of Parkinson's disease patients are warranted to determine the relationship between clinical status, medication, and TGFbeta2 concentrations.
转化生长因子(TGF)β在脑损伤周围部位的损伤修复中发挥作用。本研究检验了这样一个假设:与正常受试者相比,神经退行性疾病患者死后脑脊液(CSF)中TGFβ1和TGFβ2水平会升高。通过酶联免疫吸附测定法(ELISA)测量了帕金森病患者(n = 30)、阿尔茨海默病患者(n = 30)、多发性硬化症患者(n = 15)、精神分裂症患者(n = 12)以及正常对照者(n = 16)死后脑室脑脊液(vCSF)中的游离TGFβ1和总TGFβ2。此外,还测量了vCSF中的白蛋白、免疫球蛋白G(IgG)和总蛋白。两组之间TGFβ1和TGFβ2均存在显著差异(分别为P < 0.002和P < 0.001)。与正常对照相比,帕金森病vCSF中TGFβ1(P = 0.015)和TGFβ2(P = 0.012)均显著升高。阿尔茨海默病和多发性硬化症vCSF中TGFβ2有升高趋势,但未达到显著水平。对照者和精神分裂症患者在TGFβ1或TGFβ2方面无差异。与所有其他组相比,阿尔茨海默病vCSF中的蛋白质显著降低,这与血脑屏障通透性、年龄或自溶差异无关。有证据表明,一些TGFβ1可能从血浆漏入vCSF。发现尸检vCSF中TGFβ同工型水平与人类血清中报道的水平明显不同,尤其是TGFβ2,其在血浆中无法检测到。这些结果表明,有必要对帕金森病患者脑脊液中的TGFβ2进行进一步的体内研究,以确定临床状态、药物治疗与TGFβ2浓度之间的关系。