Objective: Sustained inflammation, which could be promoted by AB aggregation and tau hyperphosphorylation, is a critical player in Alzheimer's disease (AD) pathogenesis. In the first phase, this study was designed to evaluate the anti-inflammatory properties of Ecballium elaterium (EE), as a Mediterranean therapeutic plant, and its effects on biochemical and behavioral signs of nucleus basalis of Meynert lesioned (NBML) rats, as an approved model of AD. In the second phase, we investigated the effect of EE on nuclear factor (NF)-KB pathway which is responsible for encoding proteins involved in the inflammatory cascade. Materials and Methods: Animals were divided randomly into four groups as following: control, NBML rats (AD), AD rats that were treated by high-and low-dose EE. Prostaglandins (PGs) levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Cyclooxygenase-2 (COX-2) and acetylcholinesterase (AChE) levels were assessed by fluorometric kit and Elman method, respectively. Behavioral signs were evaluated by Morris Water Maze (MWM) test and inflammatory proteins content was analyzed by immunoblotting method. Results: According to the results, treatment of NBML rats with EE fruit juice reduced PGs and cytokines more than 2-fold in comparison with AD rats through inhibition of COX-2 enzyme. Attenuation of inflammatory response in NBML rats was accompanied by reduced AChE activity (about 3-fold) and improved learning ability. Interestingly, EE reduced NF-KB expression for about 3-fold which resulted in a more than 10-fold increase in IKBa/P-IKBa ratio. Conclusion: Our results confirmed the TNF-a/cytokines/NFKB/COX-2 pathway involves as the main inflammatory response in NBML rats. We also provided biochemical and behavioral evidence which introduces EE as an anti-inflammatory adjuvant to improve pathophysiological signs in patients suffering from AD and related dementia.

Preconditioning (PC) as a protective strategy against noxious insults can decline cell death and apoptosis. It has been approved that mitochondria play a key role in PC mechanism. The critical role of complex I (CI) in oxidative phosphorylation machinery and intracellular ROS production, particularly in the brain, accentuates its possible role in PC-induced neuroprotection. Here, differentiated PC12 cells were preconditioned with ultra-low dose LPS (ULD, 3 μ g/mL) prior to exposure to high concentration of LPS (HD, 750 μ g/mL). Our results showed that HD LPS treatment reduces cell viability and CI activity, and intensifies expression of cleaved caspase 3 compared to the control group. Intriguingly, PC induction resulted in enhancement of cell viability and CI activity and reduction of caspase3 cleavage compared to HD LPS group. In order to explore the role of CI in PC, we combined the ULD LPS with rotenone, a CI inhibitor. Following rotenone administration, cell viability significantly reduced while caspase3 cleavage increased compared to PC induction group. Taken together, cell survival and reduction of apoptosis followed by PC can be at least partially attributed to the preservation of mitochondrial CI function.

Migraine is a common chronic inflammatory neurological disease with the progressive and episodic course. Much evidence have shown a role of inflammation in the pathogenesis of migraine. Omega-3 fatty acids are an important components of cell membranes phospholipids. The intake of these fatty acids is related to decrease concentration of C-reactive protein (CRP), proinflammatory eicosanoids, cytokines, chemokines and other inflammation biomarkers. Many of clinical trials have shown the beneficial effect of dietary supplementation with omega-3 fatty acids in inflammatory and autoimmune diseases in human, including Parkinson’ s disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer’ s disease (AD), multiple sclerosis (MS) and migraine headaches. Therefore, omega-3 fatty acids as an alternative therapy can be potentially important. This review focuses on the pathogenesis of a migraine, with an emphasis on the role of omega-3 fatty acid and its molecular mechanisms.

Background: neuroinflammation and oxidative stress play a pivotal role in the diabetic neuropathic pain. The aim of this study was to evaluate the effect of aerobic exercise with melatonin on RAGE gene expression and some indicators of oxidative stress in rats with diabetic neuropathic pain Methods: Forty 8-week-old male Wistar rats (weight range 204 ± 11. 3 g) were randomly divided into five of 8 groups including: diabetic neuropathy (50 mg / kg streptozotocin intraperitoneal injection), diabetic melatonin neuropathy (mg / kg 10 melatonin daily for 6 weeks), diabetic neuropathy exercise (30 minutes of aerobic exercise at 15 meters per minute, 5 days a week for 6 weeks), diabetes melatonin neuropathy and healthy exercise and control. After confirmation of diabetic neuropathy by behavioral tests, exercise protocol and supplementation were performed. RAGE gene expression was measured by real-time technique and oxidative stress indices in spinal cord tissue by spectrophotometer. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Results: Exercise and melatonin reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia. Aerobic exercise with melatonin significantly reduced RAGE gene expression and MAD concentration and increased the activity of SOD and CAT enzymes compared to the diabetic neuropathy group (P <0. 05). Conclusion: Aerobic exercise with melatonin modulates the expression of RAGE gene and oxidative stress indices and improves the sensitivity of nociceptors to pain factors. It is recommended to use aerobic exercise with melatonin for diabetics to reduce neuropathic pain.

Objective(s): While traumatic brain injury (TBI) is a predisposing factor for development of posttraumatic epilepsy (PTE), the occurrence of seizures following brain trauma can infuriate adverse consequences of brain injury. However, the effect of seizures in epileptogenesis after mild TBI cannot yet be accurately confirmed. This study was designed to investigate the histopathological and molecular modifications induced by seizures on traumatized brain. Materials and Methods: Using a new method, head was traumatized and seizures were evoked by subconvulsive dose of pentylenetetrazole (PTZ) fifteen days after induction of focal mild TBI. Convulsion assessments were performed one hour after PTZ injection and was followed by histopathological and molecular evaluations. Results: A significantly higher score and longer duration of seizure attacks as well as higher number of epileptiform discharges were observed in the TBI+PTZ group compared to sham and TBI groups. An elevated number of apoptotic cells was observed in the TBI+PTZ group compared to sham and TBI rats. Molecular investigations revealed higher levels of Bax/Bcl2 ratio, Caspase 3, and NF-κ B in the TBI+PTZ group compared to the other animal groups. The value of Nrf2 did not change after mild TBI compared to sham and PTZ control groups. Occurrence of seizures after TBI, however, significantly decreased the level of Nrf2. Conclusion: Our data indicated that seizure occurrence following mild TBI aggravates cell injury and death via activation of neuroinflammatory processes and may increase the risk of PTE. Additionally, our results suggest a potential protective role of Nrf2 after chemically evoked PTE.