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Abstract Introduction Systemic administration of pentylenetetrazole (PTZ) causes brain damage (BD), and triggers a series of morphological and neurochemical changes, which in turn bring about behavioral, cognitive, and motor deficits. Serotonin (5-HT), dopamine (DA), and noradrenaline (NA) levels are controlled by various brain structures and these levels are related to motor activity; however, the concentration of these neurotransmitters during the postictal process remains unknown. Objective We investigated the concentration of 5-HT, NA and DA in the hippocampus, cerebellum, and cortex on motor deficit during the postictal stage. Method Eighteen male Wistar rats (300 g) assigned to two groups: control (n = 9, saline solution) and experimental (n = 9, PTZ) were used. Myoclonic shakes were counted and motor behavior assessments were recorded during three hours post PTZ injection (90 mg/kg). The cortex, cerebellum, and hippocampus of each rat were dissected to determine the 5-HT, DA, and NA concentration by high performance liquid chromatography. Results PTZ induced a significant increase in total 5-HT and DA levels in the hippocampus and cortex; in the cerebellum there was a significant increase in the concentration of 5-HT and NA. The presence of myoclonic shakes as well as a marked motor deficit in the experimental group were significantly different in comparison to the control. Discussion and conclusion 5-HT modifies the concentration of other monoamines directly involved in motor aspects such as NA and DA in the hippocampus, cerebellum, and cortex during the postictal process.
Resumen Introducción La administración sistémica de pentilentetrazol (PTZ) causa daño cerebral y desencadena una serie de cambios morfológicos y neuroquímicos que a su vez provocan déficits conductuales, cognitivos y motores. Los niveles de serotonina (5-HT), dopamina (DA) y noradrenalina (NA) son modulados por varias estructuras cerebrales y sus concentraciones se relacionan con la actividad motora; sin embargo, se desconoce la concentración de estos neurotransmisores durante el proceso postictal. Objetivo Evaluar la manera en que la concentración de 5-HT, NA y DA en el hipocampo, el cerebelo y la corteza influye en el déficit motor durante la etapa postictal. Método Se utilizaron 18 ratas macho Wistar (300 g), divididas en dos grupos: control (n = 9, solución salina) y experimental (n = 9, PTZ). Se registraron las sacudidas mioclónicas y se evaluó el comportamiento motor durante tres horas después de la inyección de PTZ (90 mg/kg). Se extrajeron la corteza, el cerebelo y el hipocampo de cada rata para determinar la concentración de 5-HT, DA y NA mediante cromatografía líquida de alta resolución. Resultados La administración de PTZ indujo un aumento significativo en los niveles totales de 5-HT y DA en el hipocampo y la corteza; en el cerebelo hubo un aumento significativo en la concentración de 5-HT y NA. Se encontró una diferencia significativa entre el grupo experimental y control con respecto a las sacudidas mioclónicas; asimismo, los animales del grupo experimental mostraron un marcado déficit motor. Discusión y conclusión La 5-HT modula la concentración de otras monoaminas involucradas directamente en aspectos motores tal como NA y DA en el hipocampo, el cerebelo y la corteza durante el proceso postictal.
ABSTRACT
BACKGROUND: Hypoxic-ischemic encephalopathy is a cause of disability in the infant population. One of the most used animal models in the hypoxic-ischemic encephalopathy in immature brain is the preparation of Levine applied by Rice in newborn rats and consists of the bond of the left common carotid artery followed by induced hypoxia. The objective of this investigation was to study the neurological effects of the bond of the left common carotid and induced hypoxia in newborn rats. METHODS: Five control rats, five sham rats and five rats with hypoxic-ischemic lesion by means of the application of Levine's preparation at 7 days of age were used. On day 42, all rats were evaluated by time of grasping, posterior reflex test and analysis of the spontaneous locomotor activity (number of bipedal movements, number of stepped stalls, grooming time). RESULTS: The lesioned group presented less grasping time, lower number of positive responses to the posterior reflex and lower number of stepped stalls (p = 0.024, 0.002 and 0.0001, respectively). There were no statistically significant differences in grooming time or number of bipedal movements. CONCLUSIONS: Newborn rats in whom Levine preparation was applied presented clinical alterations that may resemble some of the signs that accompany infantile cerebral palsy (grasp problems, wrong response to postural reflexes and alteration in locomotion).
Subject(s)
Animals , Rats , Carotid Stenosis/complications , Hypoxia, Brain/complications , Cerebral Palsy/etiology , Animals, Newborn , Rats, WistarABSTRACT
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Abstract: Infant crying is a complex phenomenon that implies several functions: breathing, action of laryngeal and supralaryngeal muscles under the control of the neurovegetative systems of the brainstem, and the limbic system, and the association of cortical areas and the cerebellum. Although it is a communication system different to babbling and language, it is related with the future development of phonation. Cry analysis provides information about the neuro-physiologic and psychological states of newborns and the identification of perinatal abnormalities. It is necessary to discuss the subject extensively because there are new data on situations such as laringomalacia, congenital hypothyroidism, deafness and sleep apnea that seem to be associated to infantile crying behaviors. Infant cries can be analyzed as behavioral conditions (hunger, anger and pain cries) allows knowing of mother-child relationship or the effect under diverse cultural conditions, such as stress, emo-tional deprivation or illness. A spectrographic analysis of the cries may identify several characteristics: threshold, latency, duration of phonation, maximum and minimum of the fundamental frequency (F0), occurrence and maximum pitch of shift, gliding, melody, biphonation, bifurcation, noise concentration, quality of the voice, double harmonic break, glottal plosives, vibratos, melody types, F0 stability and inspiratory stridor. To date, it has not been possible to establish alteration patterns. The best studied variables are F0, its harmonics and the duration of each emission; it is accepted that F0 varies between 400 and 600 Hz, during 1.4 ± 0.6s. Under such approaches, diverse alterations and risk factors have been studied: congenital alterations, malnutrition, sudden death, maternal exposition to drugs, prematurely born babies or perinatal asphyxia and disturbances of the central nervous system. Authors have reported F0 equal or less than 300 Hz in cases of sudden death or with high frequencies, near the 1000 Hz in the Cri du chat syndrome, perinatal asphyxia and other cases who died suddenly. During the cry, there is an increase of intra-abdominal pressure, heart rate and blood pressure, reduction of oxygen saturation, increase of the intra cranial-pressure, beginning of stress reactions, depletion of the energy anf oxygen reserves, such as the found in the Valsalva's maneuver. Every event of prolonged cries implies alteration of the breathing control like a Hering-Breuer reflex. Considering that some authors have proposed early vocalizations are a good predictor of deafness, in a previous paper we reported the characteristics of the cry of 20 deaf neonates. However, we were not able to demonstrate differences when comparing them with normal hearing neonates and infants, using only parametric methods. Still, we decided to go further and investgate the quality of infant cries of deaf neonates and infants. Material and methods. Twenty zero-to two-year old cases were studied; they were deaf children of both sexes; all cases were included in a follow-up program on the Human Communication Department of the National Institute of Perinatology of Mexico and were compared with 20 normal hearing children. We re-corded Brain Stem Evoked Auditory Responses (BEAR) and cry recording using a digital Sony recorder during the physical exploration. We analyzed the frequency (Hz) and duration of the espiratory cries, the duration of inspiration between two cry emissions and the characteristics of the spectrogram. Quantitative analysis. The usual estimates of means and standard variation were obtained and they were compared with one way analysis of variance. We organized typologies of frequency by means of cluster techniques (Ward method). The distribution of the duration of the periods of crying and silence was explored with a contingency tables. Qualitative analysis. Two standardized observers visually analyzed all the cries to determine any variation of F0 and of harmonic frequencies. Whenever a variation of F0 was observed, we obtained maximum and minimum frequencies, as well as average duration of each cry emission. The procedure was validated by means of the graphic comparison with a Fouries analysis. Results. Mean duration of cries in the deaf group was 0.5845 ± 0.6150 s (range 0.08-5.2 s), while in the group of normal hearing cases was 0.5387 ± 0.2631 (range 0.06-1.75 s). From the deaf group, five cases had very prolonged duration of cries, without statistical significance. The mean duration of the inspiration was 0.3962 ± 0.2326, with a range of 0.06 to 1.75 in the deaf group and of 0.4083 ± 0.1854, with a range of 0.21 at 0.96, in the controls, without difference among groups. There was no correlation between the time of espiratory cry and that of the inspiration. Three cry topologies were organized: one of shorter duration (mean 0.30 s), with 111 spectrograms, an intermediate one (mean 0.73) with 85 spectrograms and one of prolonged duration (mean 4.5 s) with spectrograms of three cases. Three topologies of the inspiratory period were obtained: one of short periods (mean 0.33 s), with 171 spectrograms, one of intermediate duration (mean 0.80 s) with 18 spectrograms and one of prolonged duration (mean 1.60 s) with three cases. There were no statistical differences of tipologies between the deaf groups and normal hearing cases. On the qualitative analysis of cries, we came across several variations which are interpreted as abnormalities: vibratos, poor melodic control, loss of fundamental frequencies, harmonic limited production, plosives, gliding, bi phonation, and a loss of intensity at end of cry emissions. These changes were also observed on the control cases, but only in a very limited number. Discussion. Cry spectrogram analysis are non invasive indicators of the neonate's neurophysiologic organization. Although cry duration varies in healthy newborns, the accepted variation for a normal range is 1.1 to 2.8 s, with standard deviations around 0.6 s. Consistent differences have not been demonstrated between risk and control groups. However, abnormal cases such as Down syndrome or severe asphyxia have very short cries, whereas on the Cri du chat syndrome the duration of cries is prolonged. Extended cries imply cardiac and respiratory risks which have been associated with later outcomes as development retardation and sudden death. There are also some questions to solve, such as the regulation and control of cry, starting from breathing mechanisms or from a sensorial afferent, mediated by hearing. The deaf infants are constituted in a study model, considering that the auditory afference is suppressed and the control of the cry is restricted to the breathing environment. In the studied spectrograms, the duration of the cry was within reported normal limits by other authors, inasmuch in the normal hearing control cases as in the deaf, except the dissident cases, but without these reaching statistical significance. Further research of brainstem function is needed for the abnormal cases with prolonged cry periods, since such cries are interpreted as an alteration of the breathing reflexes of Hering-Breuer, which might have a pathological meaning in the sense of the sob's spasm or even more severe risk factors as sleep apnea and even sudden death. The qualitative analysis in the deaf individuals demonstrated a poor quality and unstable character of melodic control, with a smaller number of harmonics. The deaf cases lost the relationship between the fundamental frequencies and their harmonics, mainly because of the participation of supraglottic structures that modulate pitch and due to the poorness of melodic control, either for monotony or due to the impossibility of returning to a normal pattern, following variations such as vibrato, plosives or noise concentration. In the cases of prolonged cries, starting from the third second, the sound intensity tends to diminish and the harmonics are lost, perhaps due to a decrease of the subglottal pressure of phonation. This finding supports the auditory control of crying related to breathing mechanisms. Conclusions. In preliminary terms, by means of the melodic analysis of the spectrograms, differences are demonstrated be-tween the cries of the deaf and of the normal hearing cases. The increase of the complexity of the melody of the cry, or their poverty, are indicative of the neuromuscular function and they may support the evaluation of phonation before language development. The study of the spectrograms of deaf individuals does not constitute an element for the detection or for diagnosis since, to date, estimators of sensibility or of specificity have not been established, but they constitute a support for its integral evaluation, with the possibility of evaluating and of improving therapeutic rehabilitation.
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Se presenta un trabajo de investigación en el cual se midió la actividad de la enzima Na+K+-ATPasa en la fracción sinaptosomal en cerebro de ratas de la Cepa Wistar expuestas en forma aguda (una exposición) y crónica (30 días consecutivos) a vapores de tolueno, (concentración de 15000 ppm en aire, durante 15 min.) en contraste con un grupo de ratas "control" expuestas al aire libre de tolueno, (estudio in vivo). Los estudios in vitro consistieron en la incubación de la fracción sinaptosomal de cerebro de rata en tubos cerrados conteniendo en el medio reactivo de tolueno a la concentración de 10mM. El cáculo de las constantes de Michaelis-Menten (Km y Vmax) fueron evaluadas en los estudios cinéticos de la enzima en las membranas sinaptosomales. Las ratas tanto de 50 como de 120 días de edad, que fueron expuestas en forma crónica a vapores de tolueno mostraron una reducción de la actividad entre 45 y 56 por ciento con respecto a la actividad del grupo control, siendo estadísticamente significativa (p<0.05). No habiendo diferencias en las ratas expuestas a tolueno en forma aguda. En los experimentos in vitro, también mostraron reducción en la actividad de la enzima podría ser un indicador de los efectos acumulativos de las propiedades físico-químicas del tolueno sobre las membranas biológicas