Protective effects of cerebrolysin against chemotherapy (carmustine) induced cognitive impairment in Albino mice

Abstract

Chemotherapy-induced cognitive impairment (CICI) comprises different neurological problems, including difficulty in learning new things, concentrating and making decisions that affect daily life activities. Clinical reports indicate that around 70% of cancer patients receiving chemotherapy suffer from cognitive impairment. The purpose of the present study is to examine the effects of widely used anticancer medication (Carmustine) on cognitive function using mice model and investigation of the neuroprotective effects of Cerebrolysin (CBN). Cerebrolysin (CBN) is a mixture of several neurotrophic factors and active peptides with anti-inflammatory, antioxidant, and neuroprotective actions. Our study aimed to establish a mice model of Carmustine (BCNU)-induced cognitive deficits and determine the protective effects of CBN. BCNU (10 mg/kg, i.v.) was administered to mice for 28 days, and behavioral parameters were measured on a weekly basis. CBN (44 and 88 mg/kg, i.p.) was administered daily from day 1 to 28 to BCNU treatment mice. All animals were sacrificed on day 29 and brain hippocampus tissues were used for biochemical, neuroinflammatory, neurotransmitters analysis. BCNU administration animals showed impaired cognition and memory, confirmed from behavioral analysis. Further, BCNU increased oxidative stress, inflammatory cytokines release and altered neurotransmitters concentration as compared to the control group (p < 0.01). However, mice treated with CBN (44 and 88 mg/kg, i.p.) significantly and dose-dependently improved cognitive functions, reduced oxidative stress markers, inflammatory cytokines and restored neurotransmitters concentration as compared to BCNU administered mice (p < 0.05). The finding of current study suggested that CBN could be the promising compound to reverse cognitive impairment associated with use of chemotherapy.

Keywords:

• Cognitive impairment
• cerebrolysin
• donepezil
• chemobrain
• chemotherapy

Acknowledgment

The authors thank Shri. Parveen Garg, Chairman of ISF College of Pharmacy, Moga, for providing adequate research facilities and fund to accomplish research work.

Ethical approval

These animals were fed with standard diet in accordance with Institutional Animal Ethics Committee (IAEC) guidelines. The experimental protocol was reviewed and approved by the Institutional Animal Ethics Committee (ISFCP/IAEC/CPCSEA/2019/431) and performed in accordance with the Indian National Science Academy (INSA) and Committee for Control and Supervision of Experiments on Animals (CPCSEA) for the use and care of experimental animals.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Self-funded project by ISF College of Pharmacy, Moga, Punjab, India.