Early neurodevelopmental reflex impairments in a rodent model of cerebral palsy

Ho, Dini; Sanches, Eduardo Farias; Sizonenko, Stéphane

doi:10.1002/jdn.10235

Cited by 6 publications

(5 citation statements)

References 49 publications

(61 reference statements)

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“…The early evaluation of the developmental milestones after neonatal injuries can give valuable information of the efficacy of the therapeutic strategies [52][53][54]. We observed a general decrease in body weight in the animals fed with a LF diet, which could be interpreted as a detrimental effect of the diet.…”

Section: Discussionmentioning

confidence: 76%

“…In order to assess the functions in the initial stage following HI injury, the animals were tested for righting and negative geotaxis reflexes and olfactory memory test at PND8 (24 h after injury), as previously described [53]. In the righting reflex testing, the pups were placed in supine position and the time, in seconds, to turn them over to prone and place all four paws on the surface was recorded at a maximal time of 10 s. Negative geotaxis provided information about the vestibular and proprioceptive functions.…”

Section: Neurodevelopmental Reflex Testingmentioning

confidence: 99%

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Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

Sanches,

van de Looij,

et al. 2023

IJMS

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Neonatal hypoxic-ischemic (HI) encephalopathy (HIE) in term newborns is a leading cause of mortality and chronic disability. Hypothermia (HT) is the only clinically available therapeutic intervention; however, its neuroprotective effects are limited. Lactoferrin (LF) is the major whey protein in milk presenting iron-binding, anti-inflammatory and anti-apoptotic properties and has been shown to protect very immature brains against HI damage. We hypothesized that combining early oral administration of LF with whole body hypothermia could enhance neuroprotection in a HIE rat model. Pregnant Wistar rats were fed an LF-supplemented diet (1 mg/kg) or a control diet from (P6). At P7, the male and female pups had the right common carotid artery occluded followed by hypoxia (8% O2 for 60′) (HI). Immediately after hypoxia, hypothermia (target temperature of 32.5–33.5 °C) was performed (5 h duration) using Criticool®. The animals were divided according to diet, injury and thermal condition. At P8 (24 h after HI), the brain neurochemical profile was assessed using magnetic resonance spectroscopy (1H-MRS) and a hyperintense T2W signal was used to measure the brain lesions. The mRNA levels of the genes related to glutamatergic excitotoxicity, energy metabolism and inflammation were assessed in the right hippocampus. The cell markers and apoptosis expression were assessed using immunofluorescence in the right hippocampus. HI decreased the energy metabolites and increased lactate. The neuronal–astrocytic coupling impairments observed in the HI groups were reversed mainly by HT. LF had an important effect on astrocyte function, decreasing the levels of the genes related to glutamatergic excitotoxicity and restoring the mRNA levels of the genes related to metabolic support. When combined, LF and HT presented a synergistic effect and prevented lactate accumulation, decreased inflammation and reduced brain damage, pointing out the benefits of combining these therapies. Overall, we showed that through distinct mechanisms lactoferrin can enhance neuroprotection induced by HT following neonatal brain hypoxia-ischemia.

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Section: Discussionmentioning

confidence: 76%

Section: Neurodevelopmental Reflex Testingmentioning

confidence: 99%

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

Sanches,

van de Looij,

et al. 2023

IJMS

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“…In agreement with our study, offspring in the arginine vasopressin PE mouse model showed no adverse effects on open-field behavior ( 6 ). The negative geotaxis test is an early behavioral test to evaluate motor development and sensory, vestibular, and proprioceptive functions and is useful and validated in the setting of various neurological and neurodevelopmental disorders (e.g., ASD and cerebral palsy) ( 18 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model

et al. 2023

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IntroductionTo investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid.MethodsPregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring.ResultsOffspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease.ConclusionThe offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

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“…Each pup was located in the center of the box and the latency of the pup to move and reach their home bedding while standing on their four paws was recorded. A maximum duration of 120 s was allowed per trial (Ho et al., 2022).…”

Section: Methodsmentioning

confidence: 99%

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats

Spalm

Sánchez

Furland

et al. 2023

Developmental Neurobiology

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Fructose is a common sweetener found in the daily diet supplemented to many processed and ultra‐processed foods and beverages. Consumption of fructose‐sweetened beverages has drastically increased in the last decades and is widely associated with metabolic disease, systemic pro‐inflammatory status, and adverse transgenerational effects. To date, the impact of maternal fructose intake in brain function of the offspring is less explored. Therefore, the aim of this study was first, to investigate adverse effects in developmental milestones of the progeny of mothers with metabolic syndrome (MetS), induced by ad libitum consumption of a 20% fructose solution, and second to identify possible molecular changes in the nervous system of the newborns associated with maternal fructose intake. Wistar rats were randomly separated into two groups with access to water or fructose (20% w/v in water) for 10 weeks. After MetS was confirmed, dams were mated with control males and continued drinking water or fructose solution during gestation. At postnatal day (PN) 1, a subgroup of offspring of each sex was sacrificed and brains were dissected for oxidative stress and inflammatory status analysis. Changes in the developmental milestones due to maternal fructose consumption were studied (PN3–PN21) in another subgroup of offspring. Sexually dimorphic effects were found on the progeny's acquisition of neurodevelopmental milestones, in brain lipid peroxidation, neuroinflammation, and antioxidative defensive response. Our results suggest that dams’ MetS, induced by fructose intake, disrupts brain redox homeostasis in female offspring and affects sensorimotor brain circuitry which may have a translational value for studying neurodevelopmental diseases.

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Early neurodevelopmental reflex impairments in a rodent model of cerebral palsy

Cited by 6 publications

References 49 publications

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

Early Neuroprotective Effects of Bovine Lactoferrin Associated with Hypothermia after Neonatal Brain Hypoxia-Ischemia in Rats

Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model

Lipid peroxidation and neuroinflammation: A possible link between maternal fructose intake and delay of acquisition of neonatal reflexes in Wistar female rats

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