Is the war on terror induced-post traumatic stress disorder; the cause of suicide attack? An approach from psycho-cognitive and neurobiological perspective

Understanding suicide attack is one of the highly complicated problems in the field of psychological disorders. Post-traumatic stress disorder (PTSD), may occur in individuals subjected to traumatic assaults like terrorism, warfare, sexual abuse or natural disaster. Individual's living within war affected area often develops PTSD, which may consequently leads to cognitive and memory impairment. The war induced PTSD patient, is under the influence of severe stress; terror and helplessness as it manipulate and retrieve the past trauma as a current threat. Substantial evidences support that PTSD patients are more prone to varying degree of neurological and psychological complications. In this correspondence, we wish to highlight the biological consequence of suicide attack from the perspective of war induced PTSD. Earlier research also supports that PTSD and suicide have some common basis like alterations in hypothalamic pituitary-adrenal axis, nitric oxide and catecholamine like norepinephrine and serotonin level. Thus it is important to uncover the risk of PTSD due to war on terror with precision towards suicide attack and minimize the detriment followed by it. PTSD through the development of depression, irritability and anger, is one amongst the major causes of suicide attack.In order to clarify the underlying psychological mechanism, there is a pressing need to address it from different aspects like disease causing synaptic plasticity and abnormal brain development. PTSD is a reaction to past traumatic events. For instance, the danger of perceived threat due to witness of deaths in a war, may develop a constellation of properties that may leads to PTSD. Usually, it initiates a sequence of behavioral and cognitive changes that can be anticipated to reduce the perceived threat. However, the consequences of perceived threat lead to cognitive changes and thus maintain a devastating disorder. Appraisals of such memory not only generate situational fear but also the avoidance, which leads to enhanced trepidation and over-activity. For example, a person exposed to a road side traumatic accident may avoid driving; for having an impractical faith that it may happen again, thereby affecting its social life.Patients suffering from PTSD due to war may interpret that the trauma will persist for long time and thus he is no longer safe. He or she may suffer from depression, irritability, anger outbursts, emotional numbing, flashbacks, and nightmares [1]. It has been reported that numbing is an ordinary reaction to traumatic events. Individuals should realize that it is a normal aspect of the recovery process, otherwise it can lead to permanent changes which may worsen their physical or psychological well-being [2-4]. Children experiencing the PTSD, usually underwent alterations in hypothalamic-pituitary-adrenal axis, catecholamine and norepinephrine, which results in pathological and detrimental brain development [5]. Interestingly, the inhibition of nitric oxide in hippocampus by antidepressant has promising outcome to alleviate the PTSD symptoms [6]. While, the augmented level of plasma nitrates in depressive patients are found to be associated with suicide attempts [7].Figure 1The intention of a suicide attack is to kill a large crowd or bringing mass destruction, even with the notion that he will die in this act. Suicide bombings termed as "suicide bombing" constitute an overall 4% of terrorist attacks, which dates back to the beginning of the 19th century. In most of the modern suicide terrorist is used against non-combatants for the accomplishment of impact on political situation. Although a suicide attack aims to annihilate a primary target, however it can be used as a weapon of psychological warfare to affect the large public population. The main target of this action is not those who are killed but those witnessed it [8]. Intriguingly, it is reported that the level of brain-derived neurotropic factor (BDNF) is directly associated with suicide while indirectly it can affect PTSD. Also, defining body of research proved that altered level of serotonin in dorsal raphe nucleus, amygdala, median raphe, frontal cortex, hypothalamus and hippocampus is associated with aggressive behavior and suicide [9]. PTSD-induce symptoms like impulsivity, violence, suicide attempts, depression, panic, and anxiety can also be associated with altered serotonin levels [10].ConclusionThe mechanism of suicide attack is still highly debated; and need much more to address. Since, PTSD through the development of depression, irritability and anger, accomplish various physiological and cognitive changes in the brain, so it might be one of the causes which increases the susceptibility of acceptance for being a volunteer to suicide attack? This discussion was put forward; as some war induced PTSD patients among temporary displaced people in different regions of the world showed strong willingness for suicide attack as a counter revenge of war. Therefore, we also need to address suicide attack from the perspective of psychological disorders like war induced PTSD

Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase

BACKGROUND AND PURPOSE: Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone. METHODS: We have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE. RESULTS: Pre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p \u3c 0.001). L-arginine significantly inverted this anticonvulsant effect (p \u3c 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p \u3c 0.05, p \u3c 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam. CONCLUSIONS: Our findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation

The role of opioid and nitrergic systems in dual modulation of seizure susceptibility

Epilepsy is a chronic disorder presented by recurrent episodes of seizures and affect worldwide individuals.  The underlying mechanism of seizure is still elusive. Hence, there is still a need to determine the contribution of various systems in neurobiology and treatment of seizure. Evidence shows that opioid and nitrergic systems within the brain interact to modulate various physiological and pathological conditions including memory, pain, reward, addiction, depression, and seizure. Various studies revealed that diverse dose of opioids such as morphine has dual modulation in seizure susceptibility. For instance, it is reported that morphine at lower doses (0.5, 1, and 3 mg/kg) exerts an anticonvulsant effect in experimental seizure models, whereas at higher doses (15, 30, and 60 mg/kg) it could exacerbate the seizure. Similarly, nitrergic system has also been observed to possess dual effects in modulating the seizure threshold. Therefore, understanding of opioidergic and nitrergic systems interaction in seizure seems important to achieve the successful goal of seizure management. This review aimed to clarify and provide insight into how opioidergic and nitrergic systems interact in brain and mediate seizure behavior.Keywords: Opioids; Nitric oxide; Seizures; Morphine

The Possible Role of Nitric Oxide and Oxidative Stress in the Enhanced Apoptosis of Cardiac Cells in Cirrhotic Rats

Abstract- Cirrhosis has been related with hyperdynamic circulation, manifesting as increased cardiac output and decreased systemic vascular resistance. In the present study we examined the cirrhosis outcome on apoptosis of rat hearts. We also tried to explore the role of nitric oxide (NO) and oxidative stress in the probable changed apoptosis of cirrhotic hearts. Twenty eight days after ligation of bile duct, heart tissues were tested for apoptosis. The extent of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been calculated in heart tissues. The cirrhotic hearts exhibited structural defects and greater apoptosis. Chronic treatment of cirrhotic rats with LNAME, a non-selective inhibitor of NO synthase, inhibited heart structural defects and reduced apoptosis of hearts. We also showed that cirrhotic rat hearts had an enhanced level of MDA and reduced activities of CAT, GSHPx and SOD. When the animals were treated by L-NAME chronically, the MDA level reduced and activities of CAT, GSHPx and SOD augmented in cirrhotic heart. In conclusion, increased apoptosis of cirrhotic hearts probably happen due to NO overproduction and increased oxidative stress in hearts of cirrhotic rats

Involvement of nitric oxide in granisetron improving effect on scopolamine-induced memory impairment in mice

AbstractGranisetron, a serotonin 5-HT3 receptor antagonist, widely used as an antiemetic drug following chemotherapy, has been found to improve learning and memory. In this study, effects of granisetron on spatial recognition memory and fear memory and the involvement of nitric oxide (NO) have been determined in a Y-maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was administered to scopolamine-induced memory-impaired mice prior to acquisition, consolidation and retrieval phases, either in the presence or in the absence of a non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a NO precursor, l-arginine (750mg/kg). It is demonstrated that granisetron improved memory acquisition in a dose-dependent manner, but it was ineffective on consolidation and retrieval phases of memory. The beneficial effect of granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750mg/kg) did not potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory acquisition phase. It is concluded that nitric oxide is probably involved in improvement of memory acquisition by granisetron in both spatial recognition memory and fear memory.This article is part of a Special Issue entitled The Cognitive Neuroscience

Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.

Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation

The effect of berberine nanomicells on hepatic cirrhosis in bile duct ligated rats

The present study was designed to investigate the possible hepatoprotective effect of berberine (BBR) nano micelles on liver cirrhosis induced by bile duct ligation model (BDL) in male rats. Introduction: The anti-fibrotic effect of chronic berberine (BBR) had previously demonstrated in a rat model of bile duct ligation (BDL) - induced liver fibrosis. As a result, the aim of present study was to investigate the possible hepatoprotective effect of BBR nanomicelles on liver cirrhosis induced by Bile duct ligation model (BDL) in male rats. Methods and Results: Male Wistar rats were divided into 7 groups (n= 6) including sham-operated, BDL + saline, BDL + nanoBBR (50 mg/kg, p.o.), BDL + nanomicelles, BDL + BBR (50 and 100 mg/kg, p.o.), BDL + silymarin (100 mg/kg, p.o.). After 21 days of drugs' treatments following bile duct ligateation, the serum and tissue levels of some hepatic markers were measured and pathologic evaluations performed.BDL could markedly increase aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) serum levels and tissue tumor necrosis factor-alpha (TNF-α), level along with reductions in tissue levels of glutathione (GSH), superoxide dismutase (SOD) and total protein levels. On the other hand, BBR nanomicelles (50 mg/kg, p.o.) and silymarin (100 mg/kg, p.o.) markedly decreased the serum levels of AST and ALT while enhanced GSH level. In addition, BBR nanomicelles (50 mg/kg, p.o.), silymarin (100 mg/kg, p.o.) and BBR (100 mg/kg, p.o.) groups showed a considerable increase in SOD levels. BBR nanomicelles (50 mg/kg, p.o.) significantly lowered TNF-α level. In addition, nanoBBR group prevented liver cirrhosis in histopathologic analysis.  Conclusions:Therefore, formulation of BBR nanomicelles may represent a good approach to enhance the effect of BBR in liver injuries

Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy

Abstract Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed nerve conduction and progressive chronic pain. Inflammatory mediators, particularly cytokines, have a determinant role in the pathogenesis of neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK), an energy charge sensor with neuroprotective properties, is decreased in diabetes. It has been reported that activation of AMPK reduces the systemic inflammation through inhibition of cytokines. In this study, we aimed to investigate the probable protective effects of AMPK on DN in a rat of diabetes. DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF-a, CRP were assessed as relevant markers for inflammatory response. Also, the expression of phosphorylated AMPK (p-AMPK) and nonphosphorylated (non-p-AMPK) was evaluated by western blotting in the dorsal root ganglia. Histopathological assessment was performed to determine the extent of nerve damage in sciatic nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg) significantly increased the MNCV and reduced the levels of inflammatory cytokines. In addition, we showed that administration of metformin increased the expression of p-AMPK as well as decline in the level of non p-AMPK. Our results demonstrated that co-administration of dorsomorphin with metformin reversed the beneficial effects of metformin. In conclusion, the results of this study demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy might be associated with the anti-inflammatory response