Rat Pups Research Articles

Neonatal paw pricking alters adolescent behavior in a sex-dependent manner and sucrose partially remediates the effects

Neonatal exposure to noxious stimuli such as repeated heel lances can cause behavior changes. In the NICU sucrose given prior to procedures attenuates the immediate behavioral response to noxious stimuli but may not ameliorate the long-term consequences, and treatment with 24 % sucrose can brain structure and behavior in adult rodents. We used a rat model to determine whether paw pricks during the neonatal period alter social interaction and/or paw withdrawal thresholds (PWT) in adolescence, and if 7 % sucrose mitigates these effects. One male and one female pup per litter was assigned to each of six experimental groups (no paw prick (control), 1 paw prick (1PP), or 2PP, ± sucrose). Hind paws were pricked once or twice each day between postnatal day (P)3 and P10. Social behavior and PWT were tested in adolescence using the modified social interaction test and von Frey filaments, respectively. Social behavior was altered in the 2PP group; total time interacting was lower in 2PP rats, primarily due to less time sniffing a play partner. Sucrose did not mitigate effects of paw prick but trended to alter social behaviors in males; it decreased time in contact but increased social motivation (movement toward a play partner). PWTs were higher in 2PP animals, this was not altered by sucrose. Thus, rat pups exposed to paw pricks in the neonatal period have some altered behaviors in adolescence. The nature of the behavioral changes is sex-dependent, but sucrose did not mitigate these changes.

Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes

BACKGROUND AND AIMSBiliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to result from a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in biliary atresia in Australian livestock, but is found in a limited location and is highly unlikely to be a significant human toxin. We hypothesized that other unsaturated carbonyl compounds, some with the potential for significant human exposure, might also be biliary toxins. METHODSWe focused on the family of microcystins, cyclic peptide toxins from blue-green algae that are found worldwide, particularly during harmful algal blooms. We used primary extrahepatic cholangiocyte spheroids and extrahepatic bile duct explants from both neonatal (a total of 86 P2 mouse pups and 18 P2 rat pups (n=8-10 per condition for both species)) and adult rodents (a total of 31 P15-18 mice (n=10-11 per condition)) to study the biliary toxicity of microcystins and potential mechanisms RESULTSWe found that 400 nM microcystin-RR, but not six other microcystins or the related algal toxin nodularin, caused greater than 80% lumen closure in cell spheroids made from extrahepatic cholangiocytes isolated from 2-3-day-old mice (p<0.0001). In contrast, it resulted in less than an average of 5% lumen closure in spheroids derived from neonatal intrahepatic cholangiocytes or cells from adult mice (p=0.4366). We also found that microcystin-RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice (p<0.0001), but not 18-day-old mice. Microcystin-RR caused a 2.3 times increase in reactive oxygen species in neonatal cholangiocytes (p<0.0001), and treatment with N-acetyl cysteine partially prevented microcystin-RR-induced lumen closure (p=0.0004), suggesting a role for redox homeostasis in its mechanism of action. CONCLUSIONSWe identify microcystin-RR as a selective neonatal extrahepatic cholangiocyte toxin and suggest that it acts by increasing redox stress.

Cerium oxide nanoparticles (nanoceria) pretreatment attenuates cell death in the hippocampus and cognitive dysfunction due to repeated isoflurane anesthesia in newborn rats

General anesthetics exposure, particularly prolonged or repeated exposure, is a crucial cause of neurological injuries. Notably, isoflurane (ISO), used in pediatric anesthesia practice, is toxic to the developing brain. The relatively weak antioxidant system at early ages needs antioxidant support to protect the brain against anesthesia. Cerium oxide nanoparticles (CeO2-NPs, nanoceria) are nano-antioxidants and stand out due to their unique surface chemistry, high stability, and biocompatibility. Although CeO2-NPs have been shown to exhibit neuroprotective and cognitive function-facilitating effects, there are no reports on their protective effects against anesthesia-induced neurotoxicity and cognitive impairments. Herein, Wistar albino rat pups were exposed to ISO (1.5 %, 3-h) at postnatal day (P)7+P9+P11, and the protective properties of CeO2-NP pretreatment (0.5 mg/kg, intraperitoneal route) were investigated for the first time. The control group at P7+9+11 received 50 % O2 (3-h) instead of ISO. Exposure to nanoceria one-hour before ISO protected hippocampal neurons of the developing rat brain against apoptosis [determined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) analysis with caspase-3, and immunoblotting with Bax/Bcl2, cleaved caspase-3 and PARP1] oxidative stress, and inflammation [determined by immunoblotting with 4-hydroxynonenal (4HNE), nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TNF-α)]. CeO2-NP pretreatment also reduced ISO-induced learning (at P28–32) and memory (at P33) deficits evaluated by Morris Water Maze. However, memory deficits and thigmotactic behaviors were detected in the agent-control group; elimination of these harmful effects will be possible with dose studies, thus providing evidence supporting safer use. Overall, our findings support pretreatment with nanoceria application as a simple strategy that might be used for pediatric anesthesia practice to protect infants and children from ISO-induced cell death and learning and memory deficits.

Pulmonary, Hepatic, and Renal Fibrosis due to Nitrofurantoin in Rat Pups

Pulmonary, Hepatic, and Renal Fibrosis due to Nitrofurantoin in Rat Pups

Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats

BackgroundChronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.ResultsHigh fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.Conclusionsβ-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.

Postnatal rearing environment alters pup cues for caregiver-offspring interactions

Maternal behavior experienced in early life provides essential scaffolding to infant psychobiology with life-long effects on neurobiological and behavioral outcomes. However, infants are not passive recipients of caregiving. Evidence in rodents suggests that pups actively contribute to dam-pup interactions by soliciting maternal care with auditory, tactile, and hormonal cues. The limited bedding and nesting material (LBN) rearing manipulation induces changes in maternal care that have been attributed to maternal stress caused by the low-resource environment. The goal of the current study was to determine whether LBN also alters pup cues for maternal behavior, with implications for the mechanism of LBN-induced effects. Rat dams and pups were randomly assigned to LBN or Control rearing conditions on postnatal day (P) 0–6 and pups were fostered to the same or different condition on P6–13. LBN increased pup-directed maternal behaviors measured through 24 h monitoring using machine learning based automated analysis. LBN altered several pup cues known to affect maternal behavior including reducing pup core body temperature, reducing body weight, and altering pup vocalizations on P6 and P12. P6–13 LBN-exposed pups had elevated serum testosterone, which positively correlated with maternal licking and grooming. LBN reduced pup movement between nest attendance onset and the start of nursing, which was negatively related to dam nursing latency and contributed to longer nursing latency in LBN dams. P0–6 pup exposure to LBN also led to longer nest attendance bouts and shorter licking and grooming bouts on P7 and P9, suggesting lasting effects of LBN on pups. These data demonstrate that LBN changes pup behavioral and hormonal signals consistent with eliciting more maternal care, contributing to augmented pup-directed behaviors. This bidirectional interplay may be a critical mechanism involved in the lasting effects of early life environments.

Recovery of ventilatory and metabolic responses to hypoxia in neonatal rats after chronic hypoxia

Chronic hypoxia (CH) during postnatal development attenuates the hypoxic ventilatory response (HVR) in mammals, but there are conflicting reports on whether this plasticity is permanent or reversible. This study tested the hypothesis that CH-induced respiratory plasticity is reversible in neonatal rats and investigated whether the initial plasticity or recovery differs between sexes. Rat pups were exposed to 3 d of normobaric CH (12 % O2) beginning shortly after birth. Ventilation and metabolic CO2 production were then measured in normoxia and during an acute hypoxic challenge (12 % O2) immediately following CH and after 1, 4–5, and 7 d in room air. CH pups hyperventilated when returned to normoxia immediately following CH, but normoxic ventilation was similar to age-matched control rats within 7 d after return to room air. The early phase of the HVR (minute 1) was only blunted immediately following the CH exposure, while the late phase of the HVR (minute 15) remained blunted after 1 and 4–5 d in room air; recovery appeared complete by 7 d. However, when normalized to CO2 production, the late phase of the hypoxic response recovered within only 1 d. The initial blunting of the HVR and subsequent recovery were similar in female and male rats. Carotid body responses to hypoxia (in vitro) were also normal in CH pups after approximately one week in room air. Collectively, these data indicate that ventilatory and metabolic responses to hypoxia recover rapidly in both female and male neonatal rats once normoxia is restored following CH.

Is anxiety and depression transmissible? Depressed mother rats transmit anxiety- and depression-like phenotypes to cohabited rat pups through gut microbiota assimilation

ObjectiveThis study is to investigate the role of gut microbiota transmission in the development of anxiety/depression in offspring exposed to maternal depression. MethodOffspring rats were cohabitated with their depressed mother or father rats (which exposed to chronic unpredictable mild stress (CUMS)) for 2, 4, and 6 months, the anxiety- and depression-like behaviors, and interaction/caring activities between mother/father and their pups were detected. The gut microbiota composition and its relationship with behaviors were analyzed. Fecal microbiota transplantation (FMT) was performed to establish the gut microbiota of depressed/normal mother rats in the offspring rats to further confirm the role of “depressive gut microbiota” transmission in mediating the anxiety/depression in the pups. ResultsAnxiety and depression phenotypes can be transmitted from depressed mother rats to their cohabited offspring. Frequent interactions and gut microbiota assimilation were observed between rat mothers and their pups. Remodeling of the gut microbiota in pups by FMT could induce or attenuate anxiety- and depression-like phenotypes depending on the origin of the fecal microbiota. By comparison, the pups cohabiting with depressed father rats exhibited milder anxiety and depression. ConclusionsThese data together support that depressed mothers can transmit anxiety/depression to their pups through gut microbiota assimilation, which is related to frequent interactions. Our study reinforces the significance of mental health of mothers in preventing the occurrence of childhood anxiety and depression, and pointing out the possibility of remodeling intestinal microbiota as an effective therapeutic approach for treating anxiety/depression in children.

Tactile Mechanisms and Afferents Underlying the Rat Pup Transport Response.

Juvenile rodents and other altricial mammals react with calming, immobility and folding up of feet to parental pickup, a set of behaviors referred to as transport response. Here we investigate sensory mechanisms underlying the rat transport response. Grasping rat pups in anterior neck positions evokes strong immobility and folding up of feet, whereas more posterior grasping positions have lesser effects on immobility and foot position. Transport responses are enhanced by slow (1Hz) and even more so by fast (4Hz) gentle shaking and translation of the pup, features consistent with parental transport. In response to lateral grasping, the forepaw below the grasping position points downwards and the forepaw lateral to the grasping position points upwards and medially. Such forepaw adjustments put the pup's center of gravity below the grasping point, optimizing pup transportability along with folding up of feet and tail lifting. Tactile stimuli on the back, belly, tail, whisker, dorsal forepaws and dorsal hind-paws do not significantly affect the behaviour of anterior-neck-held pups. Instead, ground contact or paw stimulation consistent with ground contact disrupts transport responses. We identify afferents mediating the transport response by examining membrane labelling with FM1-43 following anterior neck grasping. We observe a dense innervation of the anterior neck skin region (~30 terminals/ mm2). We also observed an age-related decrease of cytochrome oxidase reactivity in the rat somatosensory cortical neck representation, a possible correlate to the developmental decrease in the pup transport response. We conclude anterior neck grasping and loss of ground contact trigger calming and postural adjustments for parental transport in rat pups, responses putatively driven from the densely innervated anterior neck skin.

Dexmedetomidine directly binds to and inhibits Toll-like receptor 4

BackgroundWhile a number of anesthetics has been shown potentially associated with neurotoxicity in the developing brain, dexmedetomidine, a drug that was rather recently introduced into the perioperative setting, is considered beneficial from neurological wellbeing. However, the underlying mechanism of how dexmedetomidine affects brain health remains to be determined. Based on our recent study, we hypothesized that dexmedetomidine would directly bind to and inhibit Toll-like receptor 4 (TLR4), a critical receptor largely expressed in microglia and responsible for neurological insult. MethodsWe used TLR4 reporter assays to test if dexmedetomidine attenuates TLR4 activation. Furthermore, a direct binding of dexmedetomidine on TLR4 was tested using photoactivatable medetomidine. Lastly, the effect of dexmedetomidine on ketamine (anesthetic)-induced neurotoxicity was tested in rat pups (P7). ResultsWe showed that dexmedetomidine attenuated TLR4 activation using reporter assay (IC50 = 5.8 µg/mL). Photoactivatable dexmedetomidine delineated its direct binding sites on TLR4. We also showed that dexmedetomidine attenuated microglia activation both in vitro and in vivo. DiscussionWe proposed a novel mechanism of dexmedetomidine-mediated neuroprotection.

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study

BackgroundBisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. AimThis study aimed to determine how male albino rat pups’ cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. MethodsThirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. ResultsRats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. ConclusionThe structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

Neuroserpin normalization by mesenchymal stem cell therapy after encephalopathy of prematurity in neonatal rats.

Hypoxic-ischemia (HI), infection/inflammation and reperfusion injury are pathogenic factors of encephalopathy of prematurity, which involves maturational/neurotrophic disturbances in oligodendrocyte progenitor cells (OPC) and neurons/axons. Mesenchymal stem cells (MSCs) might facilitate neuroserpin production, which is neurotrophic for OPC/neurons. This study investigated MSC effects on developmental disturbances after lipopolysaccharide (LPS)-sensitized HI/reperfusion (LHIR) injury and the relation to neuroserpin expression. Postnatal day 2 (P2) rat pups received intraperitoneal LPS (5 µg/kg) injection followed by HI (unilateral common-carotid-artery ligation and 6.5% oxygen exposure for 90 min) and post-HI reperfusion (release of ligation). MSCs (5 × 104 cells) were injected into the left lateral ventricle at 24 h post-LHIR. Neurological tests and brain tissue examinations were performed between P5 and P56. After LHIR injury, MSC therapy significantly reduced cell death in subplate neurons, attenuated axonal damage, and facilitated synaptophysin synthesis in the cortex. It also alleviated OPC maturation arrest and preserved the complexity of myelinated axons in the white matter, leading to cognitive, motor and behavioral functional improvements. These beneficial effects were linked to restored neuroserpin expression in subplate neurons. MSC therapy ameliorated developmental disturbances after LHIR injury through protection of neuroserpin expression, serving as a promising approach for treating encephalopathy of prematurity. Neuroserpin is secreted by subplate neurons and may regulate the development of neurons and oligodendrocyte-axon contact for myelination in the premature brain. LPS-sensitized hypoxic-ischemia/reperfusion (LHIR) injury caused the developmental disturbances of neurons/axons and oligodendrocytes, and lowered neuroserpin levels in a neonatal rat model simulating encephalopathy of prematurity. Mesenchymal stem cell therapy alleviated the developmental disturbances after LHIR injury through protection of neuroserpin expression in subplate neurons, offering a new perspective on potential treatment for encephalopathy of prematurity.

Preparation of Organotypic Slice Cultures from a Rat Pup&amp;#39;s Hippocampus

Preparation of Organotypic Slice Cultures from a Rat Pup&amp;#39;s Hippocampus

Preparation of Organotypic Slice Cultures from a Rat Pup&amp;#39;s Hippocampus

Preparation of Organotypic Slice Cultures from a Rat Pup&amp;#39;s Hippocampus

Generating a Primary Culture of Astrocytes from a Rat Pup Brain

Generating a Primary Culture of Astrocytes from a Rat Pup Brain

Generating a Primary Culture of Astrocytes from a Rat Pup Brain

Generating a Primary Culture of Astrocytes from a Rat Pup Brain

Development and In vivo Evaluation of Atomoxetine Hydrochloride ODMTs in a Nicotine-induced Attention Deficit Hyperactivity Disorder (ADHD) Model in Rats

The current study aimed to evaluate the efficacy of orally administered rapid mini-tablets containing atomoxetine hydrochloride (ODMT) relative to the conventional capsule formulation of atomoxetine hydrochloride (ATO). To mask the bitter taste of ATO and render it more palatable for pediatric administration in individuals with Attention Deficit Hyperactivity Disorder (ADHD), an inclusion complex of ATO with β-cyclodextrin (β-CD) was synthesized. The ODMT and conventional capsule ATO formulations were administered orally to a cohort of ADHD rat pups born to nicotine-exposed dams, facilitating an in vivo efficacy assessment. Behavioral assays, including the open field test, novel object recognition test, and Barnes maze test, were conducted pre- and post-administration of the therapeutics. The outcomes suggested that the ODMT formulation, incorporating ATO-β-CD inclusion complexes, shows promise as a viable alternative to the capsule form of ATO. Conclusively, the preparation of the ATO-β-CD complexes and ODMTs leveraged a factorial experimental design, with the animal model being subjected to nicotine-induced hyperactivity to provide a unique evaluative framework for the ODMT formulation under development.Graphical

Effects of maternal subclinical hypothyroidism on neurodevelopment of offspring- an animal-based study

Background and Objective: Maternal subclinical hypothyroidism (SCH) during pregnancy is associated with adverse maternal and neonatal outcomes, including cognitive and neuropsychiatric effects. This study aimed to assess the impact of maternal SCH on young rats, examining behavioral and gross brain structure changes, and evaluating reversibility after levothyroxine treatment. Methods: This experimental animal study was conducted at the Aga Khan University for a duration of 10 months. The study was approved by the Ethical committee for Animal Care and Use. Fourteen female Sprague Dawley rats were grouped into Treated (induced with SCH, treated with levothyroxine), Untreated (induced with SCH, no treatment), and Control (administered saline). Pups' body weight was monitored, and histological procedures were conducted at postnatal days 7, 14, and 21. Behavioral tests (elevated plus maze, forced swim, and tail suspension) assessed anxiety and depression. The data was analysed using SPSS (version 25.0). The mean, median, and standard deviation were calculated for each quantitative parameter. A one-way ANOVA was performed to identify any variation in mean thyroid levels between groups, and an independent sample t-test was utilized to confirm mean differences in anxiety levels. Results: On postnatal day 7, untreated pups showed lower body weight compared to treated and control groups. This trend continued on days 14 and 21. By day 21, an elevated plus maze (EPM) test indicated anxiety-like behaviour in untreated pups, while they also exhibited more signs of depression in tests like the forced swim test (FST) and tail suspension test (TST). Brain structure, including the prefrontal cortex, remained intact in offspring affected by maternal thyroid dysfunction, with no significant changes observed in brain morphology across the groups. Conclusion: Despite unchanged brain structure, untreated rat pups exhibited significant behavioral differences indicative of depression. This underscores the importance of understanding the behavioral impacts of maternal SCH even in the absence of gross anatomical alterations.

Hypoxic-Ischemic Insult Alters Polyamine and Neurotransmitter Abundance in the Specific Neonatal Rat Brain Subregions.

Neonatal hypoxic-ischemic (HI) brain insult is a major cause of neonatal mortality and morbidity. To assess the underlying pathological mechanisms, we mapped the spatiotemporal changes in polyamine, amino acid, and neurotransmitter levels, following HI insult (by the Rice-Vannucci method) in the brains of seven-day-old rat pups. Matrix-assisted laser desorption/ionization mass spectrometry imaging of chemically modified small-molecule metabolites by 4-(anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide revealed critical HI-related metabolomic changes of 22 metabolites in 14 rat brain subregions, much earlier than light microscopy detected signs of neuronal damage. For the first time, we demonstrated excessive polyamine oxidation and accumulation of 3-aminopropanal in HI neonatal brains, which was later accompanied by neuronal apoptosis enhanced by increases in glycine and norepinephrine in critically affected brain regions. Specifically, putrescine, cadaverine, and 3-aminopropanal increased significantly as early as 12 h postinsult, mainly in motor and somatosensory cortex, hippocampus, and midbrain, followed by an increase in norepinephrine 24 h postinsult, which was predominant in the caudate putamen, the region most vulnerable to HI. The decrease of γ-aminobutyric acid (GABA) and the continuous dysregulation of the GABAergic system together with low taurine levels up to 36 h sustained progressive neurodegenerative cellular processes. The molecular alterations presented here at the subregional rat brain level provided unprecedented insight into early metabolomic changes in HI-insulted neonatal brains, which may further aid in the identification of novel therapeutic targets for the treatment of neonatal HI encephalopathy.

Comparative utility of MRI and EEG for early detection of cortical dysmaturation after postnatal systemic inflammation in the neonatal rat

BackgroundExposure to postnatal systemic inflammation is associated with increased risk of brain injury in preterm infants, leading to impaired maturation of the cerebral cortex and adverse neurodevelopmental outcomes. However, the optimal method for identifying cortical dysmaturation is unclear. Herein, we compared the utility of electroencephalography (EEG), diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI) at different recovery times after systemic inflammation in newborn rats. MethodsSprague Dawley rat pups of both sexes received single-daily lipopolysaccharide (LPS; 0.3 mg/kg i.p.; n = 51) or saline (n = 55) injections on postnatal days (P)1, 2, and 3. A subset of these animals were implanted with EEG electrodes. Cortical EEG was recorded for 30 min from unanesthetized, unrestrained pups at P7, P14, and P21, and in separate groups, brain tissues were collected at these ages for ex-vivo MRI analysis (9.4 T) and Golgi–Cox staining (to assess neuronal morphology) in the motor cortex. ResultsPostnatal inflammation was associated with reduced cortical pyramidal neuron arborization from P7, P14, and P21. These changes were associated with dysmature EEG features (e.g., persistence of delta waveforms, higher EEG amplitude, reduced spectral edge frequency) at P7 and P14, and higher EEG power in the theta and alpha ranges at P21. By contrast, there were no changes in cortical DTI or NODDI in LPS rats at P7 or P14, while there was an increase in cortical fractional anisotropy (FA) and decrease in orientation dispersion index (ODI) at P21. ConclusionsEEG may be useful for identifying the early evolution of impaired cortical development after early life postnatal systemic inflammation, while DTI and NODDI seem to be more suited to assessing established cortical changes.