Neonatal kaempferol exposure attenuates impact of cerebral palsy model on neuromotor development, cell proliferation, microglia activation, and antioxidant enzyme expression in the hippocampus of rats

ABSTRACT

Objectives

This study aims to assess the effect of neonatal treatment with kaempferol on neuromotor development, proliferation of neural precursor cells, the microglia profile, and antioxidant enzyme gene expression in the hippocampus.

Methods

A rat model of cerebral palsy was established using perinatal anoxia and sensorimotor restriction of hindlimbs during infancy. Kaempferol (1 mg/ kg) was intraperitoneally administered during the neonatal period.

Results

Neonatal treatment with kaempferol reduces the impact of the cerebral palsy model on reflex ontogeny and on the maturation of physical features. Impairment of locomotor activity development and motor coordination was found to be attenuated by kaempferol treatment during the neonatal period in rats exposed to cerebral palsy. Neonatal treatment of kaempferol in cerebral palsy rats prevents a substantial reduction in the number of neural precursor cells in the dentate gyrus of the hippocampus, an activated microglia profile, and increased proliferation of microglia in the sub-granular zone and in the granular cell layer. Neonatal treatment with kaempferol increases gene expression of superoxide dismutase and catalase in the hippocampus of rats submitted to the cerebral palsy model.

Discussion

Kaempferol attenuates the impact of cerebral palsy on neuromotor behavior development, preventing altered hippocampal microglia activation and mitigating impaired cell proliferation in a neurogenic niche in these rats. Neonatal treatment with kaempferol also increases antioxidant defense gene expression in the hippocampus of rats submitted to the cerebral palsy model.

GRAPHICAL ABSTRACT

KEYWORDS:

• Cerebral palsy
• flavonoids
• locomotion
• microglia
• hippocampus

Acknowledgements

The graphical abstract was created using BioRender.com.

Disclosure statement

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

Data availability statement

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Additional information

Funding

We are thankful to the ‘Fundação de Amparo a Ciência e Tecnologia do Estado de Pernambuco (FACEPE)’ [grant number IBPG-0588-4.05/17; AMD- 0010-4.01/19] and the ‘Tecnológico Nacional de México’ through the Program ‘Apoyos a la investigación científica y tecnológica de instituciones académicas y sector público’ [grant number 44401-01/2019] for the support. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.

Notes on contributors

Diego Bulcão Visco

D. B. Visco is a Professor at ‘Department of Biological Science and Health’, Federal University of Amapá, Macapá, Brazil. His work is developed in the field of neuroscience, physical therapy, cerebral palsy, and phenotypic plasticity.

Raul Manhães-de-Castro

R. Manhaes-de-Castro is an Emeritus Professor at Federal University of Pernambuco, Recife, Brazil. His work is developed in the field of neuroscience, nutrition and phenotypic plasticity.

Márcia Maria da Silva

M. M. da Silva is a Ph.D. student at ‘Graduate Program in Nutrition’, Federal University of Pernambuco, Recife, Brazil. Her work is developed in the field of neuroscience, nutrition, cerebral palsy, and phenotypic plasticity.

Bárbara J. R. Costa-de-Santana

B. J. R. Costa-de-Santana is a Ph.D. student at ‘Graduate Program in Neuropsychiatry and Behavioral Sciences’, Federal University of Pernambuco, Recife, Brazil. She carries out her work in the field of neuroscience, nutrition, and phenotypic plasticity.

Luís Miguel Saavedra

L. M. Saavedra is a researcher at ‘Centro de Investigación Biomédica de Michoacán’, Instituto Mexicano del Seguro Social, Morelia, Michoacán, México. He carries out his studies in the field of neuroscience and early life stress.

Maria Daniele Teixeira Beltrão de Lemos

M. D. T. B. Lemos is a Master student at ‘Graduate Program of Biochemistry and Physiology’, Federal University of Pernambuco, Recife, Brazil. She carries out her studies in the field of mitochondrial bioenergetics and oxidative stress.

Juan José Valdéz-Alarcón

J. J. Valdéz-Alarcón is a Research Professor at the Centro Multidisciplinario de Estudios en Biotecnología – Facultad de Medicina Veterinaria y Zootecnia, Universidad Michoacana de San Nicolás de Hidalgo, Tarímbaro, Michoacán, México. He carries out his work in the field of Molecular Epidemiology and Biotechnology approaches to study and control bacterial diseases in animals.

Claudia Jacques Lagranha

C. J. Lagranha is a Professor at ‘Graduate Program in Neuropsychiatry and Behavioral Sciences’, Federal University of Pernambuco, Recife, Brazil. Her work is carried out in the field of mitochondrial bioenergetics and oxidative stress.

Omar Guzman-Quevedo

O. Guzmán-Quevedo is a Professor at ‘Higher Technological Institute of Tacambaro’, Tacambaro, Mexico. He carries out his work in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the pathogenesis and therapy of metabolic disorders.

Luz Torner

L. Torner is a Titular A Researcher at ‘Centro de Investigación Biomédica de Michoacán’, Instituto Mexicano del Seguro Social, Morelia, Michoacán, México. She carries out her studies on mechanisms that operate in the brain during stress exposure to produce the vulnerability of the individual to develop psychiatric diseases.

Ana Elisa Toscano

A. E. Toscano is a Professor at ‘Nursing Unit, Vitória Academic Center’, and at ‘Graduate Program in Neuropsychiatry and Behavioral Sciences (Posneuro)’, Federal University of Pernambuco. Her work is carried out in the field of neuroscience, nutrition, cerebral palsy, and phenotypic plasticity.