Scientists have created a device that allows them to accurately measure the levels of different pro-inflammatory cytokines — molecules that mediate and regulate immune and inflammatory responses — normally found in the brain of patients with Parkinson’s disease.
The development and validation of the new device were described in the study, “Validation of an in vivo electrochemical immunosensing platform for simultaneous detection of multiple cytokines in Parkinson’s disease mice model,” published in the journal Bioelectrochemistry.
Parkinson’s disease is a progressive neurodegenerative disorder that leads to a series of motor and non-motor impairments that have a negative impact on patients’ quality of life. When treatment is initiated at later stages of the disease, it usually is less effective and more often accompanied by undesired side effects.
“[T]hus early PD [Parkinson’s disease] diagnosis is vital for delaying its progression and relieving the economic burden of the expensive treatment,” the researchers wrote.
Pro-inflammatory cytokines produced in the brains of patients with Parkinson’s as part of the body’s natural inflammatory response have emerged as potential biomarkers that could facilitate identification of the disease at its earlier stages. However, current methods used to detect and measure the levels of these cytokines are both challenging and time-consuming.
Investigators in China, in collaboration with colleagues in Australia, have developed a device that contains a glassy carbon rod sensor that is able to detect and measure the levels of three pro-inflammatory cytokines — interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) — simultaneously in living cells and in mice with Parkinson’s.
First, they placed the device’s sensor in the media of lab-cultured cells that had been treated with lipopolysaccharide (LPS), a bacteria-derived toxin, to stimulate the production of pro-inflammatory cytokines for up to 24 hours.
The device’s immunosensor indicated the levels of all three cytokines increased rapidly during the first eight hours of treatment with LPS, then stabilized, and slowly started to decrease thereafter. These findings were consistent with those obtained by Enzyme-Linked Immunosorbent Assay (ELISA), a commonly used method that allows researchers to measure the levels of specific molecules using an enzymatic reaction.
Then the team tested the device in mice that had been treated previously with MPTP, a neurotoxin often used to mimic Parkinson’s symptoms.
After placing the device’s immunosensor in the animals’ hippocampus — a brain region involved in short-term memory — researchers found that MPTP-treated mice had higher levels of pro-inflammatory cytokines when compared to sham-operated animals (controls). They also found the levels of pro-inflammatory cytokines were similar in mice treated with MPTP and in those treated with LPS, which was used to mimic a situation of acute inflammation.
As in their previous experiments with lab-cultured cells, the device’s accuracy and reliability to measure cytokine levels was confirmed by ELISA.
“The quantitative results of three cytokines obtained by this sensing device were comparable to those measured by the ELISA kits but with higher sensitivity, suggesting the accuracy, reliability, and high sensitivity of this immunosensing device,” the researchers wrote.
“This GC [glassy carbon] rod-based immunosensing device provides a universal platform for simultaneous detection of multiple cytokines in vivo, and [may potentially be used] as a deployable device such as a brain chip for continuous monitoring of multiple neurochemicals towards the early diagnosis of PD and other health conditions,” they concluded.
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