Perinatal undernutrition associated to experimental model of cerebral palsy increases adverse effects on chewing in young rats

Lacerda, Diego Cabral; Ferraz-Pereira, Kelli Nogueira; Visco, Diego Bulcão; Pontes, Paula Brielle; Chaves, Wenicios Ferreira; Guzmán-Quevedo, Omar; Manhães-de-Castro, Raul; Toscano, Ana Elisa

doi:10.1016/j.physbeh.2017.01.043

Cited by 18 publications

(13 citation statements)

References 57 publications

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“…This proof‐of‐concept preclinical study aimed at evaluating whether a 1 week treatment with human FGF19 could improve motor functions and muscle alterations in an experimental model of CP. Perinatal anoxia associated to restriction of hind paws in rats has been previously reported as a representative model for CP 7,8,10,11 . Evaluated 29 days after birth, the CP animals presented significant defects in locomotion, motor coordination and muscle strength.…”

Section: Discussionmentioning

confidence: 95%

“…Perinatal anoxia associated to restriction of hind paws in rats has been previously reported as a representative model for CP. 7 , 8 , 10 , 11 Evaluated 29 days after birth, the CP animals presented significant defects in locomotion, motor coordination and muscle strength. These damages were associated with lower body weight, smaller area and perimeter of muscle fibres, and reduced bone mass of the tibia.…”

Section: Discussionmentioning

confidence: 99%

“…CP was induced by submitting male pups to two episodes of anoxia (exposure to 100% nitrogen at 9 L/min for 12 min), on the day of birth (P0) and the day after (P1). Afterwards, from P2 to P28, sensorimotor restriction of the hind limbs was performed daily for 16 h, with free movement of the animal in the remaining 8 h of the day 7,11 . Weaning occurred at P25, and after this time, the male pups were placed in individual cages.…”

Section: Methodsmentioning

confidence: 99%

“…Afterwards, from P2 to P28, sensorimotor restriction of the hind limbs was performed daily for 16 h, with free movement of the animal in the remaining 8 h of the day. 7 , 11 Weaning occurred at P25, and after this time, the male pups were placed in individual cages. Treatment with recombinant human FGF19 (R&D System, UK) was performed from P22 to P28.…”

Section: Methodsmentioning

confidence: 99%

“… 7 , 8 In rats, this experimental CP model is characterized by reduced body growth, abnormal walking patterns, atrophy of hind limb muscles, extracellular matrix changes and joint degeneration of knee and ankle. 7 , 9 It is also associated with reduced locomotor activity, 10 increased spasticity, 9 impaired chewing 11 and motor skills, and reduced sarcomere density. 12 In addition, this experimental CP model shows brain alterations, such as an increase in the permeability of the blood–brain barrier 13 and a degraded representation of hind limbs in the primary motor cortex.…”

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy

Pereira

Benoit

Aguiar

et al. 2021

J cachexia sarcopenia muscle

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Background Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle mass and strength in mouse models with muscle atrophy. Facing the lack of therapeutics to treat locomotor dysfunctions in CP, we investigated whether FGF19 treatment could have beneficial effects in an experimental rat model of CP. Methods Cerebral palsy was induced in male Wistar rat pups by perinatal anoxia immediately after birth and by sensorimotor restriction of hind paws maintained until Day 28. Daily subcutaneous injections with recombinant human FGF19 (0.1 mg/kg bw) were performed from Days 22 to 28. Locomotor activity and muscle strength were assessed before and after FGF19 treatment. At Day 29, motor coordination on rotarod and various musculoskeletal parameters (weight of tibia bone and of soleus and extensor digitorum longus (EDL) muscles; area of skeletal muscle fibres) were evaluated. In addition, expression of specific genes linked to human CP was measured in rat skeletal muscles. Results Compared to controls, CP rats had reduced locomotion activity (−37.8% of distance travelled, P < 0.05), motor coordination (−88.9% latency of falls on rotarod, P < 0.05) and muscle strength (−25.1%, P < 0.05). These defects were associated with reduction in soleus (−51.5%, P < 0.05) and EDL (−42.5%, P < 0.05) weight, smaller area of muscle fibres, and with lower tibia weight (−38%, P < 0.05). In muscles from rats submitted to CP, changes in the expression levels of several genes related to muscle development and neuromuscular junctions were similar to those found in wrist muscle of children with CP (increased mRNA levels of Igfbp5, Kcnn3, Gdf8, and MyH4 and decreased expression of Myog, Ucp2 and Lpl). Compared with vehicle‐treated CP rats, FGF19 administration improved locomotor activity (+53.2%, P < 0.05) and muscle strength (+25.7%, P < 0.05), and increased tibia weight (+13.8%, P < 0.05) and soleus and EDL muscle weight (+28.6% and +27.3%, respectively, P < 0.05). In addition, it reduced a number of very small fibres in both muscles (P < 0.05). Finally, gene expression analyses revealed that FGF19 might counteract the immature state of skeletal muscles induced by CP. Conclusions These results demonstrate that pharmacological intervention with recombinant FGF19 could restore musculoskeletal and locomotor dysfunction in an experimental CP model, suggesting that FGF19 may represent a potential therapeutic strategy to combat the locomotor disorders associated with CP.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy

Pereira

Benoit

Aguiar

et al. 2021

J cachexia sarcopenia muscle

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Early neurodevelopmental reflex impairments in a rodent model of cerebral palsy

Sanches

Sizonenko

2022

Intl J of Devlp Neuroscience

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Cerebral palsy (CP) causes sensorimotor disabilities due to injury to the developing brain. Experimental models do not always induce the CP phenotype completely. Early neurological assessment predicts future impairments and is valuable during development. Using a rodent model characterized by brain injury caused by maternal inflammation and perinatal anoxia, and sensorimotor restriction (experimental cerebral palsy [ECP]), we describe early neurodevelopmental delays by assessing reflexes in a stage corresponding to the brain development of term infants (Postnatal Day [P] 8 in rats). Pregnant Wistar rats were injected with lipopolysaccharide (LPS; 200 μg/kg) (n = 6) or saline (n = 4) on Embryonic Days 18/19. Following delivery, 87 male and female pups were used. At P0, injured animals were exposed to anoxia for 20 0 . From P2 to P21, ECP rats were subjected to hindlimb movement restriction for 16 h/ day. ECP group had impaired righting reflex and negative geotaxis and, interestingly, performed home bedding test better than controls. From P7, ECP animals showed decreased body weight compared with controls. Overall, data provide evidence showing that this CP model based on the association of brain damage followed by sensorimotor restriction mimics CP delays and highlights the valuable information given by early neurological assessment during the establishment of the CP phenotype.

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

Visco

Castro

Silva

et al. 2022

Intl J of Devlp Neuroscience

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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.

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Perinatal undernutrition associated to experimental model of cerebral palsy increases adverse effects on chewing in young rats

Cited by 18 publications

References 57 publications

Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy

Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy

Early neurodevelopmental reflex impairments in a rodent model of cerebral palsy

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

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