Neonatal resveratrol treatment in cerebral palsy model recovers neurodevelopment impairments by restoring the skeletal muscle morphology and decreases microglial activation in the cerebellum

• Published in: Experimental neurology Vol. 378; p. 114835
• Main Authors: Pereira, Sabrina da Conceição, Manhães-de-Castro, Raul, Souza, Vanessa da Silva, Calado, Caio Matheus Santos da Silva, Souza de Silveira, Beatriz, Barbosa, Letícia Nicoly Ferreira, Torner, Luz, Guzmán-Quevedo, Omar, Toscano, Ana Elisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Animal models; Animals; Animals, Newborn; Brain injuries; Cerebellum - drug effects; Cerebellum - pathology; Cerebral Palsy - drug therapy; Cerebral Palsy - pathology; Disease Models, Animal; Female; Male; Microglia - drug effects; Microglia - pathology; Motor skills; Muscle fibers; Muscle, Skeletal - drug effects; Muscle, Skeletal - pathology; Neuroinflammation; Rats; Rats, Wistar; Recovery of Function - drug effects; Resveratrol - pharmacology; Skeletal; Stilbenes - pharmacology; Stilbenes - therapeutic use; Neuroinflammation; Animal models; Muscle fibers; Motor skills; Brain injuries; Skeletal
• ISSN: 0014-4886; 1090-2430; 1090-2430
• DOI: 10.1016/j.expneurol.2024.114835

Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary damage caused by the early insult and consequently to recover motor skills. Resveratrol has been shown to act as neuroprotection with benefits to skeletal muscle. This study aimed to investigate the effects of neonatal resveratrol treatment on neurodevelopment, skeletal muscle morphology, and cerebellar damage in CP model. Wistar rat pups were allocated to four experimental groups (n = 15/group) according CP model and treatment: Control+Saline (CS), Control+Resveratrol (CR), CP + Saline (CPS), and CP + Resveratrol (CPR). CP model associated anoxia and sensorimotor restriction. CP group showed delay in the disappearance of the palmar grasp reflex (p < 0.0001) and delay in the appearance of reflexes of negative geotaxis (p = 0.01), and free-fall righting (p < 0.0001), reduced locomotor activity and motor coordination (p < 0.05) than CS group. These motor skills impairments were associated with a reduction in muscle weight (p < 0.001) and area and perimeter of soleus end extensor digitorum longus muscle fibers (p < 0.0001), changes in muscle fibers typing pattern (p < 0.05), and the cerebellum showed signs of neuroinflammation due to elevated density and percentage of activated microglia in the CPS group compared to CS group (p < 0.05). CP animals treated with resveratrol showed anticipation of the appearance of negative geotaxis and free-fall righting reflexes (p < 0.01), increased locomotor activity (p < 0.05), recovery muscle fiber types pattern (p < 0.05), and reversal of the increase in density and the percentage of activated microglia in the cerebellum (p < 0.01). Thus, we conclude that neonatal treatment with resveratrol can contribute to the recovery of the delay neurodevelopment resulting from experimental CP due to its action in restoring the skeletal muscle morphology and reducing neuroinflammation from cerebellum. •CP model impaired the development of reflexes and locomotion in rats.•CP model alters muscle fiber types pattern and microglial activity in cerebellum.•Resveratrol in CP model reverses delay in neurodevelopment.•Resveratrol in CP restores muscular phenotype and cerebellar microglial activity.•Resveratrol does not affect motor coordination or muscle weight in a CP model.