Neonatal kaempferol exposure attenuates gait and strength deficits and prevents altered muscle phenotype in a rat model of cerebral palsy

Abstract

Cerebral palsy (CP) is characterized by brain damage at a critical period of development of the central nervous system, and, as a result, motor, behavioural and learning deficits are observed in those affected. Flavonoids such as kaempferol have demonstrated potential anti-inflammatory and neuroprotective properties for neurological disorders. This study aimed to assess the effects of neonatal treatment with kaempferol on the body development, grip strength, gait performance and morphological and biochemical phenotype of skeletal muscle in rats subjected to a model of CP. The groups were formed by randomly allocating male Wistar rats after birth to four groups as follows: C = control treated with vehicle, K = control treated with kaempferol, CP = CP treated with vehicle and CPK = CP treated with kaempferol. The model of CP involved perinatal anoxia and sensorimotor restriction of the hind paws during infancy, from the second to the 28th day of postnatal life. Treatment with kaempferol (1 mg/kg) was performed intraperitoneally during the neonatal period. Body weight and length, muscle strength, gait kinetics and Abbreviations: CP, cerebral palsy; LH, left hind paw; PA, perinatal anoxia; p-AKT, phospho-protein kinase B/AKT; p-S6, phospho-ribosomal protein S6; P, postnatal day; RH, right hind paw.

A randomized, placebo‐controlled trial evaluating the safety of excessive administration of kaempferol aglycone

“…KMP increases ATP content in vitro and in vivo (Akiyama et al, 2022 ); thus, increasing tissue ATP content by ingesting KMP may lead to improved exercise performance and reduced age‐related functional decline. KMP administration to a rat model of cerebral palsy was recently reported to attenuate gait deficits and impaired muscle strength (Visco et al, 2023 ). Although the effect of ATP on these effects was not examined in the report, the increase in ATP content due to KMP administration may have prevented muscle strength deficits.…”

Effectiveness of Polyphenols on Perinatal Brain Damage: A Systematic Review of Preclinical Studies

“…Oxygen deprivation increases the production of mitochondrial free radicals, followed by infiltration of leukocytes in the brain parenchyma. This leads to the activation of astrocytes and microglia, causing neuronal death and compromising the development of cerebral white matter [ 10 , 11 , 16 ]. Furthermore, the release of inflammatory cytokines and T-cell stimulation contribute to neuroinflammation, potentially interfering with central CNS development.…”

“…In contrast, some bioactive compounds, such as resveratrol, amentoflavone, mangiferin, and piceatannol may influence these physiological processes. Furthermore, the metabolic pathway stimulated by each compound may vary according to the properties of each [ 10 , 16 , 19 , 20 ].…”