Related Experiment Video
Updated: Jun 19, 2025
Experimental Protocol for Examining Behavioral Response Profiles in Larval Fish: Application to the Neuro-stimulant Caffeine
Published on: July 24, 2018
Impact of Early- and High-Dose Caffeine on the Cerebellum Development in Newborn Rats
Lourdes Lemus-Varela1,2, Blanca Torres-Mendoza3,4, Paola Rabago-Domingo1
1Neonatal Intensive Care Unit, Pediatric Hospital, Western Medical Center, Mexican Social Security Institute, Guadalajara, Mexico.
Insights
Early caffeine in newborns may hinder brain development. This study found caffeine, especially with oxygen, delayed cerebellar development in rat pups, impacting cell migration and connectivity.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Preterm infants often have respiratory issues, leading to early caffeine use to improve breathing and reduce lung disease.
- The impact of early caffeine on the developing cerebellum, a critical brain region for motor control and cognition, is not well understood.
Purpose of the Study:
- To investigate the effects of early caffeine administration, at standard and high doses, combined with supplemental oxygen on cerebellar development.
- To assess the impact on cell migration and the structure of the external granular layer (EGL) and molecular layer (ML) of the cerebellum.
Main Methods:
- Wistar rat pups were divided into five groups: control, placebo (oxygen), caffeine (standard dose), caffeine (standard dose) + oxygen, and caffeine (high dose) + oxygen.
- Caffeine and/or oxygen treatments were administered from the first day of life.
- Cerebellar tissues were analyzed on the 15th day of life, focusing on the EGL and ML to quantify cell migration.
Main Results:
- Caffeine administration led to delayed cerebellar development, evidenced by persistent transitional cells in the external granular layer (EGL).
- The combination of caffeine and oxygen exacerbated these delays, resulting in a thicker EGL compared to controls.
- Control groups showed more complete cell migration and a thicker molecular layer (ML).
Conclusions:
- Early caffeine administration disrupts cerebellar cortex development, affecting cell processes and neural connectivity.
- Combined caffeine and oxygen treatment intensifies these adverse effects on cerebellar development in neonatal rats.
Introduction:
Preterm newborns struggle with maintaining an adequate respiratory pattern; early caffeine administration is suggested to stimulate respiration and reduce bronchopulmonary dysplasia, however, its consequences on the immature cerebellum remains unknown. This study aimed to assess the impact of early caffeine administration, at standard and high doses, accompanied by supplemental oxygen on cerebellar development in an experimental model.
Methods:
Five groups of Wistar pups were formed (n = 8 offspring/group): (a) negative control: no intervention; (b) placebo: pups remaining from birth until the 7th day of life (DOL) exposed to fractional inspired oxygen (FiO2) 45%, resembling preterm infant condition and as a placebo, 0.2 mL oral 5% dextrose, from the first DOL until the 14th DOL; (c) caffeine group: oral caffeine, 1st DOL 20 mg/kg, and from 2nd to 14th DOL, 5 mg/kg (standard dose); (d) caffeine at the standard dose, plus O2: during the first 7 DOLs (FiO2: 45%); (e) caffeine: 40 mg/kg in the first DOL, 10 mg/kg the next 14 DOLs, plus O2 in the first 7 DOLs (FiO2: 45%). Subjects were sacrificed on their 15th DOL; measurements were taken from the cerebellum, specifically the external granular layer (EGL) and molecular layer (ML), with quantification of cell migration.
Results:
Caffeine administration in pups resulted in a delay in cerebellum development based on persistent transitional EGL cells; this finding was exacerbated in groups exposed to caffeine plus O2, as evident from the thicker EGL. The negative control group showed near-complete cell migration with a thicker ML and a significantly smaller EGL.
Conclusions:
Early caffeine administration in newborn rats disrupts cerebellar cortex cell processes and connectivity pathways, with exacerbated effects in groups receiving caffeine plus O2.
