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

Drug Chem Toxicol. 2022 Nov;45(6):2769-2779. doi: 10.1080/01480545.2021.1991195. Epub 2021 Oct 21.

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; chemobrain; chemotherapy; donepezil.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Carmustine / adverse effects
  • Carmustine / therapeutic use
  • Carmustine / toxicity
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / prevention & control
  • Cytokines
  • Disease Models, Animal
  • Mice
  • Nerve Growth Factors / therapeutic use
  • Neuroprotective Agents* / pharmacology
  • Neurotransmitter Agents

Substances

  • Antioxidants
  • Carmustine
  • cerebrolysin
  • Cytokines
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Neurotransmitter Agents