Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

Inconsistent Time-Dependent Effects of Tetramethylpyrazine on Primary Neurological Disorders and Psychiatric Comorbidities

The aim of this study was to investigate the time dependent effects of tetramethylpyrazine (TMP, main activity compound of Ligusticum chuanxiong Hort) on two neurological disorders and their neuropsychiatric comorbidities. 6 Hz corneal rapid kindling was used to induce epileptogenesis and the inflammatory pain was induced by intra-articular Complete Freund’s adjuvant (CFA) injection. The mechanical pain thresholds were measured using von Frey hair (D4, D11, D18, D25 after CFA first injection), and the vertical rearings of the mice was observed. To test the neuropsychiatric comorbidities, anxiety-like behaviors of mice were examined by open field and elevated plus maze tests. Two behavioral despair models, tail suspension test and forced swimming test were also used to evaluate the depressive like behaviors. The results showed that TMP administered from the initial day (D1-D35 in kindling model, D0-D14 and D0-D28 in CFA model) of modeling retarded both the developments of 6 Hz corneal rapid kindling epileptogenesis and the CFA induced inflammatory pain. In comparison, late periods administration of TMP (D21-D35 in kindling and D14-D28 in CFA model) showed no effect on the epileptogenesis and the generalized seizures (GS) of kindling, but alleviated maintenance of CFA induced inflammatory pain. Furthermore, we also found all TMP treatments from the initial day of modeling alleviated the co-morbid depressive and anxiety-like behaviors in both models; however, late periods treatments did not, either in kindling or the CFA induced inflammatory pain. BDNF/ERK signaling impairment was also tested by western blot, and the results showed that TMP administered from the initial day of modeling increased the hippocampal BDNF/ERK expression, whereas late period administration showed no effects. Overall, our findings reveal the inconsistent time dependent effects of Tetramethylpyrazine on neurological disorders and their relative neuropsychiatric comorbidities, and provide novel insight into the early application of TMP that might enhance hippocampal BDNF/ERK signaling to alleviate neuropsychiatric comorbidities in neurological diseases.

Author Correction: Epilepsy and neuropsychiatric comorbidities in mice carrying a recurrent Dravet syndrome SCN1A missense mutation

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

99 Barriers of Follow Up within the Burn and Wound Population.

Introduction Access to quality health care services is important for acute burn care, but comprehensive burn care goes beyond acute hospitalization. Follow up is an essential part of recovery, where providers can assess late effects of burn and help the patients with community re-integration, injury rehabilitation, and mental health. However, not all patients return for follow up after burn injury due to barriers in care and patient characteristics. We hypothesized that patients with neuropsychiatric comorbidities and 0–10% of total body surface (TBSA%) are more likely to be lost at follow up compared to patients with no neuropsychiatric comorbidities and higher TBSA. Methods A retrospective analysis was completed on patients that were admitted to a verified Burn Center from January 2016 to June 2019. Patients that were under 18 years of age and patients that died prior to discharge were excluded. Patient characteristics included were age, gender, TBSA, discharge location, payer, and comorbidities. Univariate analysis was completed using Tableau and multiple logistic regression analysis using Stata. Neuropsychiatric comorbidities were defined as dementia, alcoholism, major psychiatric disease, and drug dependence. Lost to follow up was defined as no follow up in clinic after inpatient discharge date within 1 month. Results Of 562 patients, 35.94% (n=202) were female and 65.12% (n=366) were Caucasian followed by Asian 13.7% (n=77) and Other Race 13.7% (n=77). Of the 562 patients, 157 (27.95%) were lost to follow up. After adjusting for insurance type, race, and medical comorbidities, patients with neuropsychiatric comorbidities had double the risk (OR 2.052; 1.377 - 3.057 p< 0.001) to be lost at follow up compared with those that did not have neuropsychiatric disorders. Homelessness was collinear with neuropsychiatric comorbidities suggesting an association. Patients with a TBSA >20% (n=37) were 3 times more likely to be lost at follow up in comparison with patients with 0–10% TBSA. (OR 2.921; 1.455–5.861 p< 0.003). Race, medical comorbidities, and insurance status had no significant impact on follow up. Conclusions Patients with dementia, alcoholism, major psychiatric disease, and drug dependence were more likely to be lost at follow up. Contrary to intuition, patients with burns >20% TBSA were also less likely to follow-up. Additional research is needed to better identify how psychosocial factors affect follow up in our burn patients and how to address those barriers. By focusing on our population and their needs, we can adjust our practices to make sure that we are providing holistic burn care.