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Rheumatology and Therapy Mar 2021Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on...
INTRODUCTION
Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown.
METHODS
Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH.
RESULTS
Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren's syndrome according to the American-European's classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown.
CONCLUSIONS
Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation.
PubMed: 33336287
DOI: 10.1007/s40744-020-00263-y -
ENeuro 2019is moving forward with a new initiative asking authors to present their results with estimation statistics and not to rely solely on values. In this editorial, I would...
is moving forward with a new initiative asking authors to present their results with estimation statistics and not to rely solely on values. In this editorial, I would like to introduce to you the concept of this new statistics while first discussing my evaluation of the present situation and my own experience with using statistics to interpret results, then I will propose a solution and how we will move forward in the journal. I have also included my own experience using these new statistics and provided a list of resources. This new initiative will not change what is already acceptable for statistics in the journal; it is to encourage a simple addition of using estimation statistics.
Topics: Animals; Cognition; Epilepsy; Housing; Mice; Pilocarpine; Rats; Seizures
PubMed: 31453315
DOI: 10.1523/ENEURO.0259-19.2019 -
Scientific Reports Dec 2023Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As a...
Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As a consequence, the entire tri-synaptic circuit of the hippocampus is fundamentally impaired. A key role in epileptogenesis has been attributed to the CA1 region as the last relay station in the hippocampal circuit and as site of aberrant plasticity, e.g. mediated by acquired channelopathies. The transcriptional profiles of the distinct hippocampal neurons are highly dynamic during epileptogenesis. Here, we aimed to elucidate the early SE-elicited mRNA signature changes and the respective upstream regulatory cascades in CA1. RNA sequencing of CA1 was performed in the mouse pilocarpine-induced SE model at multiple time points ranging from 6 to 72 h after the initial insult. Bioinformatics was used to decipher altered gene expression, signalling cascades and their corresponding cell type profiles. Robust transcriptomic changes were detected at 6 h after SE and at subsequent time points during early epileptogenesis. Major differentially expressed mRNAs encoded primarily immediate early and excitability-related gene products, as well as genes encoding immune signalling factors. Binding sites for the transcription factors Nfkb1, Spi1, Irf8, and two Runx family members, were enriched within promoters of differentially expressed genes related to major inflammatory processes, whereas the transcriptional repressors Suz12, Nfe2l2 and Rest were associated with hyperexcitability and GABA / glutamate receptor activity. CA1 quickly responds to SE by inducing transcription of genes linked to inflammation and excitation stress. Transcription factors mediating this transcriptomic switch represent targets for new highly selected, cell type and time window-specific anti-epileptogenic strategies.
Topics: Mice; Animals; Hippocampus; Status Epilepticus; Epilepsy, Temporal Lobe; Neurons; Pilocarpine; Transcription Factors; Disease Models, Animal
PubMed: 38092829
DOI: 10.1038/s41598-023-49310-y -
Clinical Science (London, England :... Feb 2023Increasing evidence suggests excess skin Na+ accumulation in hypertension; however, the role of skin-specific mechanisms of local Na+/water regulation remains unclear....
Increasing evidence suggests excess skin Na+ accumulation in hypertension; however, the role of skin-specific mechanisms of local Na+/water regulation remains unclear. We investigated the association between measures of sweat and trans-epidermal water loss (TEWL) with Na+ content in the skin ([Na+]skin) and clinical characteristics in consecutive hypertensive patients. We obtained an iontophoretic pilocarpine-induced sweat sample, a skin punch biopsy for chemical analysis, and measures of TEWL from the upper limbs. Serum vascular endothelial growth factor-c (VEGF-c) and a reflectance measure of haemoglobin skin content served as surrogates of skin microvasculature. In our cohort (n = 90; age 21-86 years; females = 49%), sweat composition was independent of sex and BMI. Sweat Na+ concentration ([Na+]sweat) inversely correlated with [K+]sweat and was higher in patients on ACEIs/ARBs (P < 0.05). A positive association was found between [Na+]sweat and [Na+]skin, independent of sex, BMI, estimated Na+ intake and use of ACEi/ARBs (Padjusted = 0.025); both closely correlated with age (P < 0.01). Office DBP, but not SBP, inversely correlated with [Na+]sweat independent of other confounders (Padjusted = 0.03). Total sweat volume and Na+ loss were lower in patients with uncontrolled office BP (Padjusted < 0.005 for both); sweat volume also positively correlated with serum VEGF-c and TEWL. Lower TEWL was paralleled by lower skin haemoglobin content, which increased less after vasodilatory pilocarpine stimulation when BMI was higher (P = 0.010). In conclusion, measures of Na+ and water handling/regulation in the skin were associated with relevant clinical characteristics, systemic Na+ status and blood pressure values, suggesting a potential role of the skin in body-fluid homeostasis and therapeutic targeting of hypertension.
Topics: Female; Humans; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Vascular Endothelial Growth Factor C; Angiotensin Receptor Antagonists; Pilocarpine; Angiotensin-Converting Enzyme Inhibitors; Hypertension; Sodium; Body Fluids; Water
PubMed: 36648486
DOI: 10.1042/CS20220609 -
JCI Insight Jan 2024Prolonged seizures can disrupt stem cell behavior in the adult hippocampus, an important brain structure for spatial memory. Here, using a mouse model of...
Prolonged seizures can disrupt stem cell behavior in the adult hippocampus, an important brain structure for spatial memory. Here, using a mouse model of pilocarpine-induced status epilepticus (SE), we characterized spatiotemporal expression of Lin28a mRNA and proteins after SE. Unlike Lin28a transcripts, induction of LIN28A protein after SE was detected mainly in the subgranular zone, where immunoreactivity was found in progenitors, neuroblasts, and immature and mature granule neurons. To investigate roles of LIN28A in epilepsy, we generated Nestin-Cre:Lin28aloxP/loxP (conditional KO [cKO]) and Nestin-Cre:Lin28a+/+ (WT) mice to block LIN28A upregulation in all neuronal lineages after acute seizure. Adult-generated neuron- and hippocampus-associated cognitive impairments were absent in epileptic LIN28A-cKO mice, as evaluated by pattern separation and contextual fear conditioning tests, respectively, while sham-manipulated WT and cKO animals showed comparable memory function. Moreover, numbers of hilar PROX1-expressing ectopic granule cells (EGCs), together with PROX1+/NEUN+ mature EGCs, were significantly reduced in epileptic cKO mice. Transcriptomics analysis and IHC validation at 3 days after pilocarpine administration provided potential LIN28A downstream targets such as serotonin receptor 4. Collectively, our findings indicate that LIN28A is a potentially novel target for regulation of newborn neuron-associated memory dysfunction in epilepsy by modulating seizure-induced aberrant neurogenesis.
Topics: Animals; Nestin; Pilocarpine; Seizures; Status Epilepticus; Hippocampus; Neurogenesis; Epilepsy
PubMed: 38193536
DOI: 10.1172/jci.insight.175627 -
Progress in Neurobiology Oct 2022The infiltration of immune cells is observed in the epileptogenic zone; however, the relationship between epilepsy and regulatory T cells (Tregs) remains only partially...
The infiltration of immune cells is observed in the epileptogenic zone; however, the relationship between epilepsy and regulatory T cells (Tregs) remains only partially understood. We aimed to investigate brain-infiltrating Tregs to reveal their underlying role in epilepsy. We analyzed the infiltration of Tregs in the epileptogenic zones from patients with epilepsy and a pilocarpine-induced temporal lobe epilepsy (TLE) model. Next, we evaluated the effects of brain Treg depletion on neuroinflammation, neuronal loss, oxidative stress, seizure activity and behavioral changes in the pilocarpine model. We also explored the impact of Treg expansion in the brain on seizure activity. There were a large number of Tregs in the epileptogenic zones of human and experimental epilepsy. The number of brain Tregs was negatively correlated with the frequency of seizures in patients with epilepsy. Our further findings demonstrated that brain Treg depletion promoted astrocytosis, microgliosis, inflammatory cytokine production, oxidative stress, and neuronal loss in the hippocampus after status epilepticus (SE). Moreover, brain Treg depletion increased seizure activity and contributed to behavioral impairments in experimental chronic TLE. Interestingly, intracerebroventricular injection of CCL20 amplified Tregs in brain tissue, thereby inhibiting seizure activity. Taken together, our study highlights the therapeutic potential of regulating Tregs in epileptic brain tissue.
Topics: Animals; Brain; Disease Models, Animal; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Humans; Pilocarpine; Seizures; T-Lymphocytes, Regulatory
PubMed: 35931355
DOI: 10.1016/j.pneurobio.2022.102335 -
International Journal of Molecular... Feb 2021Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present...
BACKGROUND
Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE.
METHODS
Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus.
RESULTS
The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.
Topics: Animals; Anticonvulsants; Biomarkers; Hippocampus; Inflammation; Interleukin-1beta; Lacosamide; Male; Motor Activity; Oxidative Stress; Pilocarpine; Rats, Wistar; Reactive Oxygen Species; Seizures; Status Epilepticus; Topiramate; Tumor Necrosis Factor-alpha; Rats
PubMed: 33668718
DOI: 10.3390/ijms22052264 -
Epilepsy & Behavior : E&B Sep 2021Glucose metabolism is altered in epilepsy, and this may contribute to seizure generation. Recent research has shown that metabolic therapies including the ketogenic diet...
Glucose metabolism is altered in epilepsy, and this may contribute to seizure generation. Recent research has shown that metabolic therapies including the ketogenic diet and medium chain triglycerides can improve energy metabolism in the brain. Fructose 1,6-bisphosphate (F16BP) is an intermediate of glycolysis and when administered exogenously is anticonvulsant in several rodent seizure models and may alter glucose metabolism. Here, we showed that F16BP elevated the seizure threshold in the acute 6-Hz mouse seizure model and investigated if F16BP could restore impairments in glucose metabolism occurring in the chronic stage of the pilocarpine mouse model of epilepsy. Two weeks after the pilocarpine injections, mice that experienced status epilepticus (SE, "epileptic") and did not experience SE (no SE, "nonepileptic") were injected with vehicle (0.9% saline) or F16BP (1 g/kg in 0.9% saline) daily for 5 consecutive days. At 3 weeks, mice were injected with [U-C]-glucose and the % enrichment of C in key metabolites in addition to the total levels of each metabolite was measured in the hippocampal formation and liver. Fructose 1,6-bisphosphate increased total GABA in the hippocampal formation, regardless of whether mice had experienced SE. In the hippocampal formation, F16BP prevented reductions in the % C enrichment of citrate, succinate, malate, glutamate, GABA and aspartate that occurred in the chronic stage of the pilocarpine model. Interestingly, % C enrichment in glucose-derived metabolites was reduced in the liver in the chronic stage of the pilocarpine model. Fructose 1,6-bisphosphate was also beneficial in the liver, preventing reductions in % C enrichment of lactate and alanine that were associated with SE. This study confirmed that F16BP is anticonvulsant and can improve elements of glucose metabolism that are dysregulated in the chronic stage of the pilocarpine model, which may be due to reduction of spontaneous seizures. Our results highlight that F16BP may be therapeutically beneficial for epilepsies refractory to treatment.
Topics: Animals; Anticonvulsants; Disease Models, Animal; Epilepsy; Fructose; Fructosediphosphates; Glucose; Hippocampus; Liver; Mice; Oxidative Stress; Pilocarpine; Status Epilepticus
PubMed: 34388666
DOI: 10.1016/j.yebeh.2021.108223 -
Molecular Neurobiology Dec 2022Intrahippocampal pilocarpine microinjection (H-PILO) induces status epilepticus (SE) that can lead to spontaneous recurrent seizures (SRS) and neurodegeneration in...
Intrahippocampal pilocarpine microinjection (H-PILO) induces status epilepticus (SE) that can lead to spontaneous recurrent seizures (SRS) and neurodegeneration in rodents. Studies using animal models have indicated that lectins mediate a variety of biological activities with neuronal benefits, especially galectin-1 (GAL-1), which has been identified as an effective neuroprotective compound. GAL-1 is associated with the regulation of cell adhesion, proliferation, programmed cell death, and immune responses, as well as attenuating neuroinflammation. Here, we administrated GAL-1 to Wistar rats and evaluated the severity of the SE, neurodegenerative and inflammatory patterns in the hippocampal formation. Administration of GAL-1 caused a reduction in the number of class 2 and 4 seizures, indicating a decrease in seizure severity. Furthermore, we observed a reduction in inflammation and neurodegeneration 24 h and 15 days after SE. Overall, these results suggest that GAL-1 has a neuroprotective effect in the early stage of epileptogenesis and provides new insights into the roles of exogenous lectins in temporal lobe epilepsy (TLE).
Topics: Rats; Animals; Neuroprotective Agents; Galectin 1; Rats, Wistar; Status Epilepticus; Pilocarpine; Epilepsy, Temporal Lobe; Seizures; Hippocampus; Disease Models, Animal
PubMed: 36171480
DOI: 10.1007/s12035-022-03038-4 -
Behavioural Brain Research Oct 2019The aim of this study was to evaluate in detail behavioral patterns and comorbid disturbances in rats using the lithium-pilocarpine model. A comprehensive set of...
The aim of this study was to evaluate in detail behavioral patterns and comorbid disturbances in rats using the lithium-pilocarpine model. A comprehensive set of behavioral tests was used to investigate behavioral patterns, including the open field test, Morris water maze, Y-maze, fear conditioning, the elevated plus maze, the forced swimming test, and the resident-intruder paradigm. Motor and explorative activity, learning and memory, anxiety and depressive-like behavior, aggression, and communication were evaluated 8-15 d after pilocarpine-induced status epilepticus (SE) (latent phase of the model) and 41-53 d (chronic phase) after pilocarpine-induced SE. Increased motor activity and impaired memory function were the most noticeable behavioral modifications in the epileptic rats. Both the movement speed and distance traveled increased in the open field test in both the latent and chronic phases. Significant impairments were detected in short-and long-term spatial memory in the Morris water maze during the latent phase. Besides the alterations in spatial memory, behaviors indicative of short- and long-term fear-associated memory disturbances were observed in the fear conditioning test during the chronic phase of the model. In the resident-intruder paradigm, epileptic rats exhibited disturbed communicative behavior, with impaired social behaviors. In contrast, emotional disturbances were less prominent, with the rats exhibiting decreased anxiety. There were no changes in depressive-like behavior. The data suggest that the lithium-pilocarpine model of TLE in rodents is more useful for studies of comorbid disturbances in memory, hyperactivity, and social behavior than for research on psychoemotional impairments, such as anxiety and depression.
Topics: Animals; Anxiety; Behavior, Animal; Cognition; Emotions; Epilepsy; Epilepsy, Temporal Lobe; Exploratory Behavior; Fear; Lithium; Male; Memory Disorders; Motor Activity; Pilocarpine; Rats; Rats, Wistar; Social Behavior; Spatial Memory; Status Epilepticus
PubMed: 31220488
DOI: 10.1016/j.bbr.2019.112044