Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

Relationship between body weight and hip width in dairy buffaloes (Bubalus bubalis).

The objective of the present study was to evaluate the relationship between body weight (BW) and hip width (HW) in dairy buffaloes (Bubalus bubalis). HW was measured in 215 Murrah buffaloes with a BW of 341 ± 161.6 kg, aged between three months and five years, and raised in southeastern Mexico. Linear and non-linear regressions were used to construct the prediction models. The goodness of fit of the models was evaluated using the Akaike information criterion (AIC), Bayesian information criterion (BIC), coefficient of determination (R2), mean squared error (MSE), and root MSE (RMSE). Additionally, the developed models were evaluated through internal and external cross-validation (k-folds) using independent data. The ability of the fitted models to predict the observed values was assessed based on the root mean square error of prediction (RMSEP), R2, and mean absolute error (MAE). The relationship between BW and HW showed a high correlation coefficient (r = 0.96, P < 0.001). The chosen fitted model to predict BW was: -176.33 (± 40.83***) + 8.74 (± 1.79***) × HW + 0.04 (± 0.01*) × HW2, because it presented the lowest MSE, RMSE, and AIC values, which were 1228.64, 35.05 and 1532.41, respectively. Therefore, with reasonable accuracy, the quadratic model using hip width may be suitable for predicting body weight in buffaloes.

Effect of heat stress on TNF-α, TNFRI and TNFRII expression in BLV infected dairy cattle.

High temperatures for extended periods, which do not allow animals to recover from heat stress, affect in particular those BLV-infected animals that carry a high proviral load. For this study, animals were discriminated between BLV (+) and BLV (-), and those belonging to the first group, were classified based on their proviral load. The expression of the inflammatory cytokine TNF-α and its receptors, which play an important role in disease progression, were quantified by qPCR in two different seasons. During the summer, average temperature was 19.8 °C, maximums higher than 30 °C were frequent. Instead, during the autumn, the average temperature was 12.63 °C, and temperatures never exceeded 27 °C. During this season, almost no periods of temperatures exceeded the comfort limit. Our results revealed that the expression levels of TNF-α and its receptors were downregulated in animals with high proviral load. This fact could affect their antiviral response and predispose to viral dissemination; over time, animals with a poorer immune system are prone to acquiring opportunistic diseases. Conversely, animals with LPL maintained their expression profile, with behavior comparable to non-infected animals. These findings should be considered by producers and researchers, given the problems that global warming is causing lately to the planet.

Advances in infrared thermography: Surgical aspects, vascular changes, and pain monitoring in veterinary medicine.

One of the main functions of infrared thermography (IRT) consists in detecting temperature changes in organisms caused by variations in surface blood circulation. IRT is a useful tool that has been used mainly as a diagnostic method for various stress-causing pathologies, though recent suggestions indicate that it can be used to assess the block quality of certain body regions. In the field of anaesthesiology, IRT has been applied to brachial and epidural blocks, while in algology, changes in surface blood circulation associated with sympathetic activity have been investigated. Thermography has also been employed to complement pain level scales based on the facial expressions of patients in critical condition, or after surgery. In addition, it has been used as a tool in research designed to evaluate different surgical procedures in human medicine, as in the case of surgical burrs for placing dental implants, where IRT helps assess the degree of heating associated with bone devascularisation, reduction in vascular perfusion as a consequence of stroke, and changes in the autonomous nervous system, or the degree of vascular changes in flaps applied to burn patients. In veterinary medicine, thermography has brought several benefits for animals in terms of evaluating lesions, diseases, and surgical procedures. The aim of this review is to evaluate how IRT can be used as a tool in surgical procedures, cases of vascular change, and pain monitoring in veterinary medicine with an emphasis on small animals.

Study on the suitability of life cycle assessment for the estimation of donkey milk environmental impact.

In the last decades, western Countries increased their interest in innovative products like donkey milk and other activities carried out with donkeys (onotherapy, onotourism). Donkey milk is considered a high-added-value food and is very similar to human breast milk. It is also used as an ingredient in cosmetics. The growing public interest suggests the need for a pilot study on the sustainability of donkey milk production, according to Life Cycle Assessment (LCA) criteria. Milk was used as the Declared Functional Unit (DFU) and two different models were described, a Real Scenario Model (RSM, i.e. a farm with its declared milk yield), and an Increased Milk Production Model (IMPM, i.e., the same farm with theoretically increased milk yield). Allocation was applied both in RSM and IMPM; thus, different values of impact categories, i.e., Global Warming Potential (GWP, kg CO2 equivalents), Acidification Potential (ACP, g SO2 equivalents) and Eutrophication Potential (EUP, g PO43-) were observed. GWP improved after mass allocation and showed the lowest equivalents in IMPM, compared to economic and reference allocation criterion (P < 0.05). In RSM, allocations affected GWP in a different way: the smaller size of the DFU resulted in the largest estimation of CO2 equivalents (P < 0.05) for reference allocation, whereas the mass allocation estimates were lower than with economic allocation (P < 0.05). ACP and EUP followed the same trends. No differences were found in IMPM results across the three allocation methods used. Moreover, mass allocation values recorded in RSM did not significantly differ from IMPM. ACP and EUP of RSM improved after economic allocation, although they were less sustainable (P < 0.05) than all IMPM values and RSM equivalents after mass allocation (P < 0.05). As expected, the theoretical model with increased milk yield improved the sustainability of the system. Both scenarios were affected by allocation criteria. In RSM, the economic and mass allocations described a representative scenario where donkey meat contributed to subtracting equivalents from milk (the main product). The present paper is a pilot study estimating for the first time the environmental impact of donkey milk production, with the aim to stimulate further research.

Assessment of the nociceptive response to the use of cannabidiol alone and in combination with meloxicam through infrared pupillometry in female dogs undergoing elective ovariohysterectomy.

The negative effects of pain are a constant concern in the surgical management of animals, leading to the search for new drugs or more effective analgesic protocols to control this negative emotion. This study aimed to evaluate the nociceptive response of cannabidiol (CBD) alone and in combination with meloxicam using infrared pupillometry in female dogs undergoing elective ovariohysterectomy (OVH) under isoflurane anesthesia. A total of 60 female dogs of different breeds were included. These dogs were randomly assigned to four study groups according to the treatment: Control Group (G0: n = 15) receiving saline solution; group premedicated with meloxicam at a dose of 0.2 mg Kg-1 IV (GMelox: n = 15). Postoperatively this drug was used at 0.1 mg Kg-1 IV every 24 h; the CBD-treated Group (GCBD: n = 15) at a dose of 2 mg Kg-1 orally in the preoperative. Postoperatively was administrated every 12 h; and the Group premedicated with the combination of meloxicam and CBD (GMelox/CBD: n = 15) Meloxicam at a dose of 0.2 mg Kg-1 IV preoperatively, and 0.1 mg Kg-1 IV during the postoperative. CBD at a dose of 2 mg Kg-1 orally in the preoperative, and every 12 h in the postoperative. Treatments were administered for 48 postoperative hours. After OVH, the pupillary neurologic index, pupillary size, minimum diameter (MIN), percentage change, constriction latency (Lat), constriction velocity, and maximum constriction velocity were recorded as pupillometric variables in both eyes during events (E): Baseline (30 min before drug administration), E30 min, E1h, E2h, E3h, E4h, E8h, E12h, E24h, and E48h. The Short-Form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) was used to assess pain during the same events. Overall, it was observed that the pupillometric variables Size, MIN., and Lat. were significantly higher in G0 compared to the other groups during E30 min, E1h, and E2h (p = 0.03), indicating greater pupil dilation in G0 animals. Additionally, no statistically significant differences were observed in GCMPS-SF between GMelox, GCBD, and GMelox/CBD during the postoperative period (p > 0.05). In contrast, the scores were statistically different compared to G0 (p = 0.00001), where all animals in this group received rescue analgesia at 2 h post-surgery. According to pupillometry and scores on the GCMPS-SF scale, it was observed that monotherapy with cannabidiol provides a similar analgesic effect to meloxicam alone or in combination with cannabidiol to manage acute pain in dogs. Similarly, these findings suggest that infrared pupillometry could be a tool for recognizing acute pain in dogs.

Correlation of Blood Hemoglobin Values with Non-Invasive Co-Oximetry Measurement of SpHb in Dogs Undergoing Elective Ovariohysterectomy.

Cardiovascular function monitoring has been suggested as a key parameter to determine patient stability during the anesthetic process. However, the use of pulse co-oximetry has been suggested as a technology to complement the monitoring of this system as a direct way to assess hemoglobin (Hb) blood concentration. Therefore, this study aimed to correlate and determine the measurement bias between Hb blood levels with continuously determined blood hemoglobin concentration (SpHb) and arterial oxygen content values (SpOC), both obtained by noninvasive co-oximetry in dogs undergoing elective ovariohysterectomy (OVH). A total of 85 clinically healthy bitches of different breeds that were admitted for elective OVH surgery were evaluated. These animals underwent SpHb and SpOC capture after the in vivo setting for the duration of the surgical procedure. Likewise, five minutes before the end of the surgical procedure, a blood sample was obtained directly from the jugular vein to determine the blood concentration of Hb (HbLAB). The Bland-Altman analysis showed 95% limits of agreement from -4.22 to 4.99 g/dL with a BIAS (mean difference) of 0.384 ± 2.35 g/dL (r = 0.401). SpHb recordings were correlated with oxygen saturation (SpO2) (r = 0.995), SpOC (r = 0.992) and with perfusion index (PI) (r = 0.418). Therefore, SpHb presents a moderate positive correlation with direct blood concentration of Hb. This possibly shows that continuous measurement of SpHb by noninvasive co-oximetry is a reliable and advanced alternative for monitoring Hb concentration in dogs under anesthesia.

Hypothalamic Neuromodulation of Hypothermia in Domestic Animals.

When an organism detects decreases in their core body temperature, the hypothalamus, the main thermoregulatory center, triggers compensatory responses. These responses include vasomotor changes to prevent heat loss and physiological mechanisms (e.g., shivering and non-shivering thermogenesis) for heat production. Both types of changes require the participation of peripheral thermoreceptors, afferent signaling to the spinal cord and hypothalamus, and efferent pathways to motor and/or sympathetic neurons. The present review aims to analyze the scientific evidence of the hypothalamic control of hypothermia and the central and peripheral changes that are triggered in domestic animals.

Anatomical and functional basis of facial expressions and their relationship with emotions in horses.

An emotion is defined as the affective response to a stimulus that leads to specific bodily changes, enabling individuals to react to positive or negative environmental conditions. In the absence of speech, emotions in animals are primarily studied by observing expressive components, such as facial expressions. This review aims to analyze the available literature on the influence of environmental stimuli on measurable behaviors in horses, describing the anatomical components involved in perception at the central nervous system level and the efferent pathways that trigger facial muscle contraction or relaxation, thus altering facial expressions. Additionally, articles addressing the function of facial expressions in communication are discussed, emphasizing their role in social interactions in this species. While there is limited research on equine neurophysiology, considering the common structure of the limbic system in most mammals, studies conducted on canines and primates were taken into account. In conclusion, the article underscores the importance of understanding equine facial expressions to assess their emotional states and, by extension, their welfare.

Human animal relationships in Bos indicus cattle breeds addressed from a Five Domains welfare framework.

The present review has two objectives, the first is to investigate the differences in temperament between Bos indicus and Bos taurus breeds and determining the effects on production due to positive treatment and to compare this with negative HAR, by using the Five Domain Model as framework. The second objective is to discuss potential strategies to achieve better HAR when working with Bos indicus cattle. Bos indicus are more reactive and temperamental than Bos taurus cattle. When human animal relationships (HAR) are evaluated, Bos indicus cattle may react with greater intensity. They may be more likely to develop a negative emotional state, especially in extensively raised Bos indicus cattle that are handled only a few times each year. Bos indicus cattle can have positive emotional states when they have frequent positive interactions with people. Interactions with people, both positive and negative, would be in the fourth Domain of the Five Domains model. Cattle that are more reactive during handling may also have lower weight gain, even when they have abundant feed. This would be in the first Domain of Nutrition. When cattle are handled in races and corrals, injuries may be more likely to occur. Injuries and bruises would be in the third Domain of Health. Injuries could be caused by either poor handling practices by people or poor handling facilities. Yelling or electric prod use would be examples of poor HAR. Second Environmental Domain issues may be broken facilities or slick, slippery floors that are associated with falls.

Anatomy and Physiology of Water Buffalo Mammary Glands: An Anatomofunctional Comparison with Dairy Cattle.

The present review aims to analyze the anatomical and physiological characteristics of the mammary gland and udders of water buffalo by making an anatomofunctional comparison with dairy cattle. It will also discuss the knowledge generated around the physiological regulation of milk ejection in the water buffalo. It was found that buffalo's average udder depth and width is approximately 20 cm smaller than Bos cattle. One of the main differences with dairy cattle is a longer teat canal length (around 8.25-11.56 cm), which highly influences buffalo milking. In this sense, a narrower teat canal (2.71 ± 0.10 cm) and thicker sphincter muscle are associated with needing higher vacuum levels when using machine milking in buffalo. Moreover, the predominant alveolar fraction of water buffalo storing 90-95% of the entire milk production is another element that can be related to the lower milk yields in buffalo (when compared to Bos cattle) and the requirements for prolonged prestimulation in this species. Considering the anatomical characteristics of water buffalo's udder could help improve bubaline dairy systems.

Tactile, Auditory, and Visual Stimulation as Sensory Enrichment for Dairy Cattle.

Several types of enrichment can be used to improve animal welfare. This review summarizes the literature on the use of mechanical brushes, tactile udder stimulation, music, and visual stimuli as enrichment methods for dairy cows. Mechanical brushes and tactile stimulation of the udder have been shown to have a positive effect on milk yield and overall behavioral repertoire, enhancing natural behavior. Classical music reduces stress levels and has similarly been associated with increased milk yield. A slow or moderate tempo (70 to 100 bpm) at frequencies below 70 dB is recommended to have this positive effect. Evidence on the impacts of other types of enrichment, such as visual stimulation through mirrors, pictures, and color lights, or the use of olfactory stimuli, is equivocal and requires further study.

Trait sensitivity to stress and cognitive bias processes in fish: A brief overview.

Like other animals, fish have unique personalities that can affect their cognition and responses to environmental stressors. These individual personality differences are often referred to as "behavioural syndromes" or "stress coping styles" and can include personality traits such as boldness, shyness, aggression, exploration, locomotor activity, and sociability. For example, bolder or proactive fish may be more likely to take risks and present lower hypothalamo-pituitary-adrenal/interrenal axis reactivity as compared to shy or reactive individuals. Likewise, learning and memory differ between fish personalities. Reactive or shy individuals tend to have faster learning and better association recall with aversive stimuli, while proactive or bold individuals tend to learn more quickly when presented with appetitive incentives. However, the influence of personality on cognitive processes other than cognitive achievement in fish has been scarcely explored. Cognitive bias tests have been employed to investigate the interplay between emotion and cognition in both humans and animals. Fish present cognitive bias processes (CBP) in which fish's interpretation of stimuli could be influenced by its current emotional state and open to environmental modulation. However, no study in fish has explored whether CBP, like in other species, can be interpreted as long-lasting traits and whether other individual characteristics may explain its variation. We hold the perspective that CBP could serve as a vulnerability factor for the onset, persistence, and recurrence of stress-related disorders. Therefore, studying fish's CBP as a state or trait and its interactions with individual variations may be valuable in future efforts to enhance our understanding of anxiety and stress neurobiology in animal models and humans.

Application of Infrared Thermography in the Rehabilitation of Patients in Veterinary Medicine.

Infrared Thermography (IRT) has become an assistance tool in medicine and is used to noninvasively evaluate heat elimination during and after inflammatory processes or during the recovery period. However, its application in veterinary patients undergoing physiotherapy is a field that requires deep research. This review aims to analyze the application of IRT in the monitoring of animal physiotherapy, using the thermal changes that are present in patients undergoing gait or lameness issues (e.g., inflammation, pain, increased local temperature) as a neurobiological basis. Rehabilitation techniques such as acupuncture, physical therapies, thermotherapy, photo-biomodulation, and electrostimulation have been reported to have an anti-inflammatory effect that decreases the amount of local heat production, which is heat that can be recorded with IRT. Therefore, IRT could be used as a complementary tool to evaluate the effectiveness of the therapy, and it is suggested that further studies evaluate the accuracy, sensibility, and sensitivity of IRT.

The Impact of Vegan Diets on Indicators of Health in Dogs and Cats: A Systematic Review.

There has been an increase in vegetarianism and veganism in human populations. This trend also appears to be occurring in companion animals, with guardians preferring to feed their animals in accordance with their own dietary values and choices. However, there has been controversy amongst vets and online commentators about the safety of feeding vegan diets to carnivorous species, such as cats and dogs. In spite of this controversy, to date there has been no systematic evaluation of the evidence on this topic. A systematic search of Medline, Scopus, and Web of Science was performed, identifying 16 studies on the impact of vegan diets on cat and dog health. Studies were appraised for quality using established critical appraisal tools or reporting guidelines. There was considerable heterogeneity in the outcomes measured, and study designs employed, with few studies evaluating key outcomes of interest. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was utilized for assessment of certainty in the evidence, with the evidence for most outcomes being assessed as low or very low. Whilst the quality and amount of evidence needs to be considered in formulating recommendations, there was no overwhelming evidence of adverse effects arising from use of these diets and there was some evidence of benefits. It is, however, recommended that future high-quality studies, with standardized outcome measures and large sample sizes, be conducted. At the current time, if guardians wish to feed their companion animals vegan diets, a cautious approach should be taken using commercially produced diets which have been formulated considering the nutritional needs of the target species.

Euthanasia and Pain in Canine Patients with Terminal and Chronic-Degenerative Diseases: Ethical and Legal Aspects.

Euthanasia is commonly performed in veterinary medicine to humanely induce the death of an animal when its quality of life is affected by pain or chronic degenerative diseases. The choice of euthanasia is a bilateral decision that represents a challenge for both the veterinarian and the owner of the animal due to the close emotional human-animal bond. Currently, there is legislation that can orient veterinarians concerning euthanasia and the causes that would justify this resolution. However, it is still controversial, and deciding it as the last available resort requires considering it from a medical, legal, and moral perspective. Therefore, this review aims to explore the ethical and legal implications of euthanasia in canine patients. It will analyze the reason that can justify euthanasia in animals with pain or terminal and chronic degenerative diseases, highlighting the importance of effective communication, ethical knowledge, and consideration of euthanasia as a multimodal resolution.

Thermal Response of Laboratory Rats (Rattus norvegicus) during the Application of Six Methods of Euthanasia Assessed by Infrared Thermography.

Refinement is one of the principles aiming to promote welfare in research animals. The techniques used during an experimental protocol, including euthanasia selection, must prevent and minimize suffering. Although the current euthanasia methods applied to laboratory rodents are accepted, the controversial findings regarding the potential stress/distress they can cause is a field of research. The objective was to assess the thermal response of Wistar rats during various euthanasia methods using infrared thermography (IRT) to determine the method that prevents or diminishes the stress response and prolonged suffering. Pentobarbital (G1), CO2 (G2), decapitation (G3), isoflurane (G4), ketamine + xylazine (G5), and ketamine + CO2 (G6) were evaluated at five evaluation times with IRT to identify changes in the surface temperature of four anatomical regions: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). Significant differences (p < 0.05) were found in G2 and G4, registering temperature increases from the administration of the drug to the cessation of respiratory rate and heart rate. Particularly, isoflurane showed a marked thermal response in T°ocu, T°ear, T°dor, and T°tai, suggesting that, in general, inhalant euthanasia methods induce stress in rats and that isoflurane might potentially cause distress, an effect that must be considered when deciding humane euthanasia methods in laboratory rodents.

Assessment of Vitality, Blood Profile, and Degree of Meconium Staining on the Skin in Newborn Dogs According to Its Birth Weight.

Neonatal mortality in dogs reaches up to 40%. Due to the high rates, promptly detecting the causes and preventing newborns from dying are extremely important. Vitality evaluation, blood parameters, and the degree of meconium staining on the skin are valuable resources in canine perinatology. In this study, 435 puppies from 85 bitches close to parturition were recruited and divided into four quartiles according to the puppy's birth weight: Q1 (127-200 g) n = 110 puppies, Q2 (201-269 g) n = 108 puppies, Q3 (270-388 g) n = 108 puppies, and Q4 (389-464 g) n = 109 puppies. This experimental article aimed to report the effect of birth weight on the blood profile variables, the vitality of newborn puppies, and the meconium staining degree, integrating these three aspects. It was concluded that the weight of newborns was correlated with the degree of meconium staining, presenting more cases of severe meconium staining in the puppies of the highest birth weight group. The weight of the newborns was correlated with a higher number of stillbirths and alterations in the blood variables, showing the most severe cases of metabolic acidosis, hypoxia, and hypoglycemia in the puppies of the Q4 quartile. On the contrary, no statistically significant correlations were found between the weight of newborns and vitality. Nevertheless, the analysis of the results showed that the most vigorous puppies were found at Q1; however, at minute 60 after birth (AB), all the puppies in the four quartiles standardized their vitality scores.

Rat Grimace Scale as a Method to Evaluate Animal Welfare, Nociception, and Quality of the Euthanasia Method of Wistar Rats.

Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression.

Cardiorespiratory and Neuroprotective Effects of Caffeine in Neonate Animal Models.

Caffeine is widely used to improve neonatal health in animals with low vitality. Due to its pharmacokinetics and pharmacodynamics, caffeine stimulates the cardiorespiratory system by antagonism of adenosine receptors and alteration in Ca+2 ion channel activity. Moreover, the availability of intracellular Ca+2 also has positive inotropic effects by increasing heart contractibility and by having a possible positive effect on neonate vitality. Nonetheless, since neonatal enzymatic and tissular systems are immature at birth, there is a controversy about whether caffeine is an effective therapy for newborns. This review aims to analyze the basic concepts of caffeine in neonatal animal models (rat and mouse pups, goat kids, lambs, and piglets), and it will discuss the neuroprotective effect and its physiological actions in reducing apnea in newborns.