Browsing by Author "Tavares, Isaura"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
- Neural control of the lower urinary tract during hydrocephalusPublication . Louçano, Marta; Coelho, Ana; Chambel, Sílvia; Cruz, Célia Duarte; Tavares, IsauraNeurological impairments may affect the neural control of the Lower Urinary Tract (LUT), due to structural and functional changes. Hydrocephalic patients usually present a triad of symptoms, which include gait disturbances, dementia and urinary incontinence. The consequences of hydrocephalus in brain structures, namely those involved in neural control of micturition remain mostly unknown. We used a validated animal model of hydrocephalus (rats injected in the cisterna magna with kaolin) to study the neuronal control of the LUT in hydrocephalus, focusing on two circumventricular areas: the Locus Coeruleus (LC) and the Periaqueductal grey (PAG). Studying neuronal activation of the PAG, a decrease in the number of fos-immunoreactive IR cells in the group of hydrocephalic animals was observed. Analysing the different column of the PAG separately, it was observed that this reduction was statistically significant only in ventrolateral PAG (VLPAG). During hydrocephalus the levels of tyrosine hydroxylase (TH, enzyme involved in noradrenaline biosynthesis) increase in the LC, which may affect surrounding areas, namely the Pontine Micturition Center (PMC). To analyse if hydrocephalic animals present changes in noradrenaline levels at the spinal cord which may affect micturition, the expression of dopamine beta-hydroxylase (DBH), another enzyme involved in noradrenaline biosynthesis, in L6 spinal cord sections, was evaluated by immunohistochemistry. Hydrocephalic animals showed a higher number of fibres immunoreactive to DBH. Cystometric analysis of hydrocephalic animals, 8 weeks after induction, was used to evaluate the bladder’s function. It was found that hydrocephalic animals show an increase both in the number of bladder contractions and of minimum pressure. These results suggest alterations in the brain-bladder control network leading to an exaggerated micturition reflex. Considering the significant role of PAG in the voiding reflex, its lower activation may lead to miscommunication with other areas involved in the network, namely the PMC or LC. Noradrenergic projections from the LC are responsible for the coordination between bladder contractions and EUS relaxation during voiding. Our study shows an increase in the levels of DBH in the Onuf’s nucleus. It is possible that the increased availability of the limiting enzyme in the synthesis of noradrenaline contributes to the increased number of bladder contractions during hydrocephalus.
- Noradrenergic pathways involved in micturition in an animal model of hydrocephalus—Implications for urinary dysfunctionPublication . Louçano, Marta; Coelho, Ana; Chambel, Sílvia Sousa; Prudêncio, Cristina; Cruz, Célia Duarte; Tavares, IsauraHydrocephalus is characterized by enlargement of the cerebral ventricles, accompanied by distortion of the periventricular tissue. Patients with hydrocephalus usually experience urinary impairments. Although the underlying etiology is not fully described, the effects of hydrocephalus in the neuronal network responsible for the control of urination, which involves periventricular areas, including the periaqueductal gray (PAG) and the noradrenergic locus coeruleus (LC). In this study, we aimed to investigate the mechanisms behind urinary dysfunction in rats with kaolin-induced hydrocephalus. For that purpose, we used a validated model of hydrocephalus—the rat injected with kaolin in the cisterna magna—also presents urinary impairments in order to investigate the putative involvement of noradrenergic control from the brain to the spinal cord Onuf’s nucleus, a key area in the motor control of micturition. We first evaluated bladder contraction capacity using cystometry. Since our previous characterization of the LC in hydrocephalic animals showed increased levels of noradrenaline, we then evaluated the noradrenergic innervation of the spinal cord’s Onuf’s nucleus by measuring levels of dopamine β-hydroxylase (DBH). We also evaluated the expression of the c-Fos protooncogene, the most widely used marker of neuronal activation, in the ventrolateral PAG (vlPAG), an area that plays a major role in the control of urination by its indirect control of the LC via pontine micturition center. Hydrocephalic rats showed an increased frequency of bladder contractions and lower minimum pressure. These animals also presented increased DBH levels at the Onuf´s nucleus, along with decreased c-Fos expression in the vlPAG. The present findings suggest that impairments in urinary function during hydrocephalus may be due to alterations in descending noradrenergic modulation. We propose that the effects of hydrocephalus in the decrease of vlPAG neuronal activation lead to a decrease in the control over the LC. The increased availability of noradrenaline production at the LC probably causes an exaggerated micturition reflex due to the increased innervation of the Onuf´s nucleus, accounting for the urinary impairments detected in hydrocephalic animals. The results of the study provide new insights into the neuronal underlying mechanisms of urinary dysfunction in hydrocephalus. Further research is needed to fully evaluate the translational perspectives of the current findings.
- Pain modulation from the Locus Coeruleus in a model of hydrocephalus: searching for oxidative stress-induced noradrenergic neuroprotectionPublication . Louçano, Marta; Oliveira, Joana; Martins, Isabel; Vaz, Rui; Tavares, IsauraPain transmission at the spinal cord is modulated by noradrenaline (NA)-mediated actions that arise from supraspinal areas. We studied the locus coeruleus (LC) to evaluate the expression of the cathecolamine-synthetizing enzyme tyrosine hydroxylase (TH) and search for local oxidative stress and possible consequences in descending pain modulation in a model of hydrocephalus, a disease characterized by enlargement of the cerebral ventricular system usually due to the obstruction of cerebrospinal fluid flow. Four weeks after kaolin injection into the cisterna magna, immunodetection of the catecholamine-synthetizing enzymes TH and dopamine-β-hydroxylase (DBH) was performed in the LC and spinal cord. Colocalization of the oxidative stress marker 8-OHdG (8-hydroxyguanosine; 8-OHdG), with TH in the LC was performed. Formalin was injected in the hindpaw both for behavioral nociceptive evaluation and the immunodetection of Fos expression in the spinal cord. Hydrocephalic rats presented with a higher expression of TH at the LC, of TH and DBH at the spinal dorsal horn along with decreased nociceptive behavioral responses in the second (inflammatory) phase of the formalin test, and formalin-evoked Fos expression at the spinal dorsal horn. The expression of 8-OHdG was increased in the LC neurons, with higher co-localization in TH-immunoreactive neurons. Collectively, the results indicate increased noradrenergic expression at the LC during hydrocephalus. The strong oxidative stress damage at the LC neurons may lead to local neuroprotective-mediated increases in NA levels. The increased expression of catecholamine-synthetizing enzymes along with the decreased nociception-induced neuronal activation of dorsal horn neurons and behavioral pain signs may indicate that hydrocephalus is associated with alterations in descending pain modulation.