Traumatic brain injury extending to the striatum alters autonomic thermoregulation and hypothalamic monoamines in recovering rats.

The brain cortex is the structure that is typically injured in traumatic brain injury (TBI) and is anatomically connected with other brain regions, including the striatum and hypothalamus, which are associated in part with motor function and the regulation of body temperature, respectively. We investigated whether a TBI extending to the striatum could affect peripheral and core temperatures as an indicator of autonomic thermoregulatory function. Moreover, it is unknown whether thermal modulation is accompanied by hypothalamic and cortical monoamine changes in rats with motor function recovery. The animals were allocated into three groups: the sham group (sham), a TBI group with a cortical contusion alone (TBI alone), and a TBI group with an injury extending to the dorsal striatum (TBI + striatal injury). Body temperature and motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, rats were euthanized to measure the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) levels using high-performance liquid chromatography (HPLC). We observed that TBI with an injury extending to the dorsal striatum increased core and peripheral temperatures. These changes were accompanied by a sustained motor deficit lasting for 14 days. Furthermore, there were notable increases in NA and 5-HT levels in the brain cortex and hypothalamus both 3 and 20 days after injury. In contrast, rats with TBI alone showed no changes in peripheral temperatures and achieved motor function recovery by the 7th day post-injury. In conclusion, our results suggest that TBI with an injury extending to the dorsal striatum elevates both core and peripheral temperatures, causing a delay in functional recovery and increasing hypothalamic monoamine levels. The aftereffects can be attributed to the injury site and changes to the autonomic thermoregulatory functions.

Chronic H3R activation reduces L-Dopa-induced dyskinesia, normalizes cortical GABA and glutamate levels, and increases striatal dopamine D1R mRNA expression in 6-hydroxydopamine-lesioned male rats.

RATIONALE: Dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), are the major complication in the pharmacological treatment of Parkinson's disease. LIDs induce overactivity of the glutamatergic cortico-striatal projections, and drugs that reduce glutamatergic overactivity exert antidyskinetic actions. Chronic administration of immepip, agonist at histamine H3 receptors (H3R), reduces LIDs and diminishes GABA and glutamate content in striatal dialysates (Avila-Luna et al., Psychopharmacology 236: 1937-1948, 2019). OBJECTIVES AND METHODS: In rats unilaterally lesioned with 6-hydroxydopamine in the substantia nigra pars compacta (SNc), we examined whether the chronic administration of immepip and their withdrawal modify LIDs, the effect of L-Dopa on glutamate and GABA content, and mRNA levels of dopamine D1 receptors (D1Rs) and H3Rs in the cerebral cortex and striatum. RESULTS: The administration of L-Dopa for 21 days induced LIDs. This effect was accompanied by increased GABA and glutamate levels in the cerebral cortex ipsi and contralateral to the lesioned SNc, and immepip administration prevented (GABA) or reduced (glutamate) these actions. In the striatum, GABA content increased in the ipsilateral nucleus, an effect prevented by immepip. L-Dopa administration had no significant effects on striatal glutamate levels. In lesioned and L-Dopa-treated animals, D1R mRNA decreased in the ipsilateral striatum, an effect prevented by immepip administration. CONCLUSIONS: Our results indicate that chronic H3R activation reduces LIDs and the overactivity of glutamatergic cortico-striatal projections, providing further evidence for an interaction between D1Rs and H3Rs in the cortex and striatum under normal and pathological conditions.

Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury.

Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.

GABAergic imbalance is normalized by dopamine D1 receptor activation in the striatum contralateral to the cortical injury in motor deficit-recovered rats.

RATIONALE: The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function, which may be modulated by dopamine. OBJECTIVES: We studied whether the activation of dopamine D1 receptors (D1Rs) modulates the γ-aminobutyric acid (GABA) and glutamate levels in the striatum of recovered rats at 192 h after cortical injury. METHODS: The D1R agonist SKF-38393 (0, 2, 3, or 4 mg/kg) was administered at 24, 48, 96, and 192 h post-injury, and then rats were decapitated to determine GABA and glutamate levels and the levels of D1R mRNA on both sides of the striatum. RESULTS: GABAergic imbalance in the striatum contralateral to the injury site was normalized by the administration of the D1R agonist, but this treatment did not produce a significant effect on glutamate levels, suggesting that glutamate was metabolized into GABA. The administration of SKF-38393 (2 mg/kg) decreased the levels of D1R mRNA in the striatum contralateral to the injury, and this effect was blocked by the coadministration of the D1R antagonist SCH-23390 (2 mg/kg). In the striatum ipsilateral to the injury, the D1R agonist increased the D1R mRNA levels, an effect that was blocked by SCH-23390. CONCLUSION: The reversal of the GABAergic imbalance in the striatum contralateral to the cortical injury can be modulated by extrastriatal D1R activation, and the D1R agonist-induced increases in the D1R mRNA levels in the striatum ipsilateral to the injury suggest that the striatum may be necessary to achieve functional recovery.

Chronic administration of the histamine H3 receptor agonist immepip decreases L-Dopa-induced dyskinesias in 6-hydroxydopamine-lesioned rats.

RATIONALE: Histamine H3 receptors (H3Rs) are co-expressed with dopamine D1 receptors (D1Rs) by striato-nigral medium spiny GABAergic neurons, where they functionally antagonize D1R-mediated responses. OBJECTIVES AND METHODS: We examined whether the chronic administration of the H3R agonist immepip modifies dyskinesias induced by L-3,4-dihydroxyphenylalanine, L-Dopa (LIDs), in rats lesioned with 6-hydroxydopamine in the substantia nigra pars compacta, and the effect of D1R and H3R co-activation on glutamate and GABA content in dialysates from the dorsal striatum of naïve rats. RESULTS: The systemic administration (i.p.) of L-Dopa for 14 days significantly increased axial, limb, and orolingual abnormal involuntary movements (AIMs) compared with the vehicle group. The chronic administration of the H3R agonist immepip alongside L-Dopa significantly decreased axial, limb, and orolingual AIMs compared with L-Dopa alone, but AIMs returned to previous values on immepip withdrawal. Chronic immepip was ineffective when administered prior to L-Dopa. The chronic administration of immepip significantly decreased GABA and glutamate content in striatal dialysates, whereas the administration of L-Dopa alone increased GABA and glutamate content. CONCLUSIONS: These results indicate that chronic H3R activation reduces LIDs, and the effects on striatal GABA and glutamate release provide evidence for a functional interaction between D1Rs and H3Rs.

Association of risk factors with primary open angle glaucoma in adults over the age of 40 / Asociación de los factores de riesgo con glaucoma primario de ángulo abierto en mayores de 40 años.

Objective: To determine the association of systemic diseases, as well as smoking and alcohol with primary open-angle glaucoma (POAG) in adults over 40 years age. Method: A revision of the records of patients older than 40 years aged who had been diagnosed with glaucoma, which were selected at the outpatient care dept. Information was obtained through the automated hospital information system, which included socio-demographic and clinical variables. Data base was created and was processed by SPSS V20 program. Results: 1,020 patient, 548 (53.7%) with a diagnosis of POAG, mean age of patients 73.2 ± 11.16 years, of which 193 (35.2%) were male and 355 (64.8%) female. A significant relationship was found between POAG and increasing age (p = 0.000), diabetes mellitus (p = 0.056) and hypertension (p = 0.098). While no relationship was found between POAG and cancer, smoking and alcohol intake was found. Conclusions: These results display the need of carrying out more specific studies of causal type to establish best possible partnerships and thus carry out prevention programs for early diagnosis.

Objetivo: Determinar la asociación de las enfermedades sistémicas, así como la ingesta de alcohol y tabaquismo, con glaucoma primario de ángulo abierto (GPAA) en adultos mayores de 40 años. Método: Se revisaron los expedientes de pacientes mayores de 40 años de primera vez con diagnóstico de glaucoma que asistieron al servicio de oftalmología del Instituto Nacional de Rehabilitación. La información se consiguió mediante el sistema automatizado de información hospitalaria, que incluyó variables sociodemográficas y clínicas. Se creó una base de datos y se realizó el análisis con el programa SPSS V20. Resultados: 1,020 sujetos, 548 (53.7%) con diagnóstico de GPAA, edad promedio 73.2 ± 11.16 años, y de ellos 193 (35.2%) varones y 355 (64.8%) mujeres. Se pudo establecer asociaciones significativas entre GPAA y edad (p = 0.000), diabetes mellitus (p = 0.056) e hipertensión arterial (p = 0.098), pero no se encontró asociación entre GPAA y cáncer, tabaquismo ni ingesta de alcohol. Conclusiones: Es necesario realizar estudios de tipo causal más específicos para establecer de mejor forma las posibles asociaciones, y de esta manera llevar a cabo programas de prevención para su diagnóstico a edad temprana.

Dopamine D1 receptor activation maintains motor coordination in injured rats but does not accelerate the recovery of the motor coordination deficit.

The sensorimotor cortex and the striatum are interconnected by the corticostriatal pathway, suggesting that cortical injury alters the striatal function that is associated with skilled movements and motor learning, which are functions that may be modulated by dopamine (DA). In this study, we explored motor coordination and balance in order to investigate whether the activation of D1 receptors (D1Rs) modulates functional recovery after cortical injury. The results of the beam-walking test showed motor deficit in the injured group at 24, 48 and 96h post-injury, and the recovery time was observed at 192h after cortical injury. In the sham and injured rats, systemic administration of the D1R antagonist SCH-23390 (1mg/kg) alone at 24, 48, 96 and 192h significantly (P<0.01) increased the motor deficit, while administration of the D1R agonist SKF-38393 alone (2, 3 and 4mg/kg) at 24, 48, 96 and 192h post-injury did not produce a significant difference; however, the co-administration of SKF-38393 and SCH-23390 prevented the antagonist-induced increase in the motor deficit. The cortical+striatal injury showed significantly increased the motor deficit at 24, 48, 96 and 192h post-injury (P<0.01) but did not show recovery at 192h. In conclusion, the administration of the D1R agonist did not accelerate the motor recovery, but the activation of D1Rs maintained motor coordination, confirming that an intact striatum may be necessary for achieving recovery.

Dopamine D1 receptor activation maintains motor coordination and balance in rats.

Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's disease, produces motor impairment. The basal ganglia, cerebellum and cerebral cortex are interconnected, have functional roles in motor coordination, and possess dopamine D1 receptors (D1Rs), which are expressed at a particularly high density in the basal ganglia. In this study, we examined whether the activation of D1Rs modulates motor coordination and balance in the rat using a beam-walking test that has previously been used to detect motor coordination deficits. The systemic administration of the D1R agonist SKF-38393 at 2, 3, or 4 mg/kg did not alter the beam-walking scores, but the subsequent administration of the D1R antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which were reversed by the full agonist SKF-82958. The co-administration of SKF-38393 and SCH-23390 did not alter the beam-walking scores compared with the control group, but significantly prevented the increase in beam-walking scores induced by SCH-23390. The effect of the D1R agonist to prevent and reverse the effect of the D1R antagonist in beam-walking scores is an indicator that the function of D1Rs is necessary to maintain motor coordination and balance in rats. Our results support that D1Rs mediate the SCH-23390-induced deficit in motor coordination.

D1 Antagonists and D2 Agonists Have Opposite Effects on the Metabolism of Dopamine in the Rat Striatum.

The striatum is known to possess high levels of D1-like and D2-like receptors (D1Rs and D2Rs, respectively). We have previously shown that selective inhibition of D1Rs increases the dopaminergic metabolic response and proposed that this effect is associated with the concomitant activation of postsynaptic D2Rs by endogenous dopamine (DA). Here, we examined whether activation of D2Rs modulates the metabolism and synthesis of DA in the striatum. We used male Wistar rats to evaluate the effects of the systemic administration of a D2R agonist (bromocriptine), a D1R antagonist (SCH-23390), and the co-administration of these compounds with pargyline on the inhibition of monoamine oxidase. DA and L-3,4-dihidroxyphenylacetic acid (DOPAC) levels and 3,4-dihydroxy-L-phenylalanine (L-DOPA) content were measured using high performance liquid chromatography. The systemic administration of SCH-23390 alone, at 0.25, 0.5, 1 or 2 mg/kg, significantly (P < 0.05) increased DOPAC levels and the DOPAC/DA ratio. At 2, 4 and 8 mg/kg, the administration of bromocriptine alone significantly (P < 0.05) decreased DOPAC levels, L-DOPA content and the DOPAC/DA ratio, whereas at 2 mg/kg, it decreased DA levels. In both groups, co-administration of either SCH-23390 or bromocriptine with pargyline decreased DOPAC levels and the DOPAC/DA ratio by approximately 70 % compared to the levels observed in the control groups. In conclusion, administration of the D2R agonist bromocriptine decreased dopaminergic synthesis and metabolism in the striatum; in contrast, administration of the D1R antagonist SCH-23390 induced the opposite effects.

A COL2A1 gene polymorphism is related with advanced stages of osteoarthritis of the knee in Mexican Mestizo population.

Primary osteoarthritis (OA) is a multifactorial disease with several genetics factors involved. The COL2A1 gene is of particular interest because it encodes for the most abundant protein in articular cartilage. The aim was to evaluate the association of COL2A1 gene polymorphism with OA of the knee in Mexican Mestizo patients. A case-control study was conducted; cases comprised patients with a radiologic scoring > or = 2 and controls with a radiologic scoring <2. DNA was extracted from a peripheral blood sample, the polymorphic site of the COL2A1 gene was submitted to polymerase chain reaction (PCR), and the products were digested using PvuII restriction enzyme. For statistical analysis, a non-conditional logistic regression was developed. There were no associations among alleles in the overall sample, nevertheless, a significant association was found with p (Pp/pp) allele and OA of the knee grade 4 [odds ratio (OR), 95% confidence interval (CI 95%) 4.1 (1.2-14.6)] adjusted by gender, age, and body mass index (BMI). These results suggest an association of a COL2A1 gene polymorphism with advanced stages of OA of the knee in Mexican Mestizo population.

Incontinentia pigmenti (IP2): familiar case report with affected men. Literature review.

UNLABELLED: Incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects skin, teeth, eyes and may also have neurological problems. The IP2 name describes the histological characteristics, the incontinence of melanin into the melanocytes cells in the epidermal basal layer and its presence in superficial dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the first time. In a physical exploration she presented sparse and thin hair, eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth have a conic crown and there was also a delayed eruption of other teeth, right eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions and brownish-gray lesions in a lineal pattern. The patient s father had hypopigmented lesions in the posterior regions of both legs. The oral clinical and radiographic exams showed diverse anomalies. Both the patient's and the father's chromosomal studies were normal. DISCUSSION: In the present case we can see that the father has IP2 without supernumeraries X, with the antecedent that his mother had something similar. It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential modulator) gene to a classical one, which was found in some affected men. It is necessary to carry out a molecular study of these patients.