PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study.

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project "PerBrain" is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients' clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients' informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients' neurological status and their caregivers' mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456 . Registered 15 March 2021 - Retrospectively registered.

Regulatory effect of caffeic acid phenethyl ester on type I collagen and interferon-gamma in bleomycin-induced pulmonary fibrosis in rat.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-γ) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 µmol/kg/day, respectively). (5: Sham group: CAPE (10 µmol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-γ level, increase the animals' body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis.

The study of antinociceptive effect of hydroalcoholic extract of Teucrium oliverianum (a plant used in southern Iranian traditional medicine) in rat by formalin test.

OBJECTIVE: Antinociceptive and anti-inflammatory activities of hydroalcoholic extract of Teucrium Oliverianum were investigated by formalin test model. This study was conducted in on the male Wistar rats, weighting 150-180 g. The animals were divided into seven groups (n = 7) and received 200, 400, 600 and 800 mg kg(-1) of hydroalcoholic extract of teucrium oliverianum intraperitoneally, respectively. Negative control group received normal saline (5 mL kg(-1)) and the positive control groups received 2.5 mg kg(-1) morphine and 300 mg kg(-1) aspirin, intraperitoneally respectively. The results showed that all doses of extract have significant analgesic effect (p < 0.05) in all studies times in comparison with negative control. The best result achieved with 600 mg kg(-1) of extract. The result revealed that the analgesic effect of the extract (600 mg kg(-1)) \was less than aspirin (300 mg kg(-1)) on the second phase of pain and less than morphine (2.5 mg kg(-1)) in both phases of the pain, more than aspirin in first phase of pain. One group of animals was treated with naloxone (1 mg kg(-1), i.p.) and suitable dose of extract (600 mg kg(-1), i.p.). Also, Naloxone inhibited analgesic effect of alcoholic extract of Teucrium Oliverianum. It can be concluded that the alcoholic extract of Teucrium oliverianum may exert its effect through opioid receptors, stimulating GABAergic system or promotes the release of endogenous opipeptides or decreasing free radicals.

Effect of hydroalcoholic extract of Lavandula officinalis on nicotine-induced convulsion in mice.

Epilepsy an important CNS (central nervous system) problem that about 1% of world's population suffer of it. The aim of study was to evaluate of anticonvulsant effect of hydroalcoholic extract of Lavandula officinalis. In this study, anticonvulsant activity of the hydroalcoholic extract of Lavandula officinalis (L. officinalis) was studied against chemoconvulsant-induced seizures in male mice. Lavandula officinalis (100, 200, 400, 600 and 800 mg kg(-1)), diazepam (0.15 mg kg(-1)) and normal saline (10 mL kg(-1)) were injected intraperitoneally, respectively in different groups of mice, 30 min before nicotine (5 mg kg(-) i.p.). The onset time intensity and duration of convulsions and the percentage of death were recorded. Also the time-response (0, 15, 30, 45, 60 min before nicotine injection) for most effective dose of plant extract (600 mg kg(-1)) was investigated. The results showed that hydroalcoholic extract of Lavandula officinalis had anticonvulsant effect. The most effective dose of plant extract was 600 mg kg(-1). In time-response study for the most effective dose of extract (600 mg kg(-1)), the onset, duration and intensity of convulsion significantly (p < 0.05) increased, decreased and decreased, respectively for all tested times. The best response observed in 30, 45 and 60 min. The results showed significant anticonvulsant effect for hydroalcoholic extract of Lavandula.

Effect of diltiazem on retention and retrieval of memory in young and aged mice.

Diltiazem (DTZ) is widely used in the prophylaxis of hypertension and treatment of angina. The effects of DTZ and other calcium channel blockers on memory have been discussed with several procedures and different theories have been suggested. In the present study, the effect of DTZ on retention and retrieval of memory in young and aged mice was investigated by using the passive avoidance apparatus. For this purpose, after weighting, coding and classifying the mice, they were grouped as follow: test group received electric shock plus DTZ (10 and 30 mg kg(-1), i.p.), blank group received electric shock plus normal saline and control group received only electric shock. In all three groups delay time of leaving the platform for both retention and retrieval test of memory was measured. DTZ was administered immediately after receiving electric shock in the retention test, but in retrieval test DTZ was administered 24 h after receiving electric shock. The results indicated that 30 mg kg(-1) of DTZ impaired retention and retrieval of young mice memory. The 30 mg kg(-1) of DTZ enhanced retention while 10 and 30 mg kg(-1) of it improved retrieval of aged mice memory.

A comparison study of effects of Echinacea extract and levamisole on phenytoin-induced cleft palate in mice.

There are many reports that the teratogenic effects of phenytoin, especially cleft palate can be decreased by stimulation of maternal immune system. Also, there is some evidence that Echinacea extract and levamisole are immunomodulator drugs. So, in this study, we compared the prophylactic effects of levamisole and Echinacea extract on teratogenic effects of phenytoin. This study was performed on 32 pregnant mice that were divided into four groups. The first group (control group) received normal saline intraperitoneally and the other groups (test groups) received phenytoin (65 mg/kg intraperitoneally) at 10th day of gestation. Levamisole and extract of Echinacea purpurea were administrated at dose of 10 and 360 mg/kg intraperitoneally, respectively, in along with and 12h later after phenytoin injection, in two groups. Fetuses were carried out in 19th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate incidence was 16, 5.3, and 3.2% in fetuses of mice that received only phenytoin, phenytoin with levamisole, and phenytoin with Echinacea extract, respectively. Mean weight and length of fetuses of animals that received levamisole and Echinacea extract were significantly greater than those received only phenytoin. It is concluded that Echinacea can stimulate immune system more than levamisole and has better prophylactic effect on incidence of phenytoin-induced cleft palate, but it is not significant.

Effect of vitamins C and E on cognitive function in mouse.

The aim of this study was to verify the role of Vitamins C and E on the cognitive function of young and aged mice. First and second groups of young animals (aged 3 months) received either Vitamin E (250mg/kg per day) or Vitamin C (300mg/kg per day) for 60 days. Third group was treated with the combination of Vitamin E (250mg/kg per day) and Vitamin C (300mg/kg per day) for 60 days. The control group received only vehicle. The aged animal group (aged 15 months) were treated as the young group. Passive avoidance method was used for the assessment of cognitive function in both young and aged animals. The results indicated a significant improvement in the cognitive function of aged mice while there were no significant changes in young animals.

Modification of drug-induced catatonia and tremors by quapazine in rats and mice.

Administration of perphenazine, tremorine, nicotine and harmine induced Parkinson-like symptoms in rats and mice. The efficacy of quipazine, a serotonin agonist, in antagonizing these drug-induced Parkinsonian symptoms was assessed. Combinations of this drug with other antiparkinsonian agents such as scopolamine, diphenhydramine and amantadine were also studied in the manifestation of Parkinson-like symptoms in the animal models. The results indicate that quipazine, a central serotonergic agent, counteracted some of the drug-induced symptoms of pseudoparkinsonism in laboratory animals. Cholinergic, dopaminergic and histaminergic receptors play an important role in the manifestations of these symptoms.