Cerebrolysin provides effective protection on high glucose-induced neuropathy in cultured rat dorsal root ganglion neurons

Abstract

Cerebrolysin, an endogenous peptide with neuroprotective and neurotrophic properties, indicated to be beneficial on diabetic neuropathy by preliminary clinical and experimental studies but without evidence on central or peripheral action. Dorsal root ganglion (DRG) neurons, based on involvement of pain sensation in both health and disease as first relay centers for transmission and processing of peripheral nociceptive sensory signals, was used to investigate possible effects of Cerebrolysin on high glucose-induced neuropathy, as model. DRG’s were obtained from adult rats and the isolated neurons were seeded on E-Plate®’s equipped with gold microelectrodes, and incubated in culture media in a CO₂ incubator at 37 C. DRGs were exposed to high glucose (50 mM) in the absence and presence of different concentrations of Cerebrolysin ® (2–40 mg/ml). Cell index (derived from cell viability and neurite outgrowth) was recorded with Real-Time Cell Analyzer and was used as primary outcome measure. High glucose-induced cellular neuropathy and neuroprotective effects of Cerebrolysin was evaluated from area under the curve (AUC) of cell index-time graphs. Exposure of DRG neurons to high glucose caused a rapid and persistent decrease in the mean AUC values compared to normoglycemic controls. Co-treatment with Cerebrolysin (40 mg/ml) attenuated this high glucose-induced effect in a concentration-dependent manner. In normoglycemic conditions, treatment with Cerebrolysin caused a dose-dependent increase in the mean AUC values. Cerebrolysin treatment resulted in maintenance of the functional integrity, survival, and promotion of neurite outgrowth of the cultured DRG neurons exposed to high glucose, indicating involvement of peripheral sensory neurons.

Keywords:

• Cerebrolysin
• dorsal root ganglion
• sensory neuropathy
• diabetes

Disclosure statement

No potential conflict of interest was reported by the author(s). Regarding funding sources; the other are working in academic positions (as stated in affiliations with the roles of lecturer, scientist and physician) and get salary through money that the University receives from the government. The research laboratory infrastructure available at the Karadeniz Technical University was used, but the fpauthors received no internal or external financial support for this research, data analysis, decision to submit the article for publication, preparation of the manuscript, authorship or publication of this article.

Data availability statement

Data presented in this manuscript file will be available upon reasonable request to Ahmet Ayar ([email protected]), it is not made publically available because the software required to process raw data has access limitations and license requirement.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.