Efficacy of some non-conventional herbal medications (sulforaphane,tanshinone IIA,and tetramethylpyrazine) in inducing neuroprotection in comparison with interleukin-10 after spinal cord injury: A meta-analysis

Context

Inflammation after spinal cord injury (SCI) may be responsible for further neural damages and therefore inhibition of inflammatory processes may exert a neuroprotection effect.

Objectives

To assess the efficacy of some non-conventional herbal medications including sulforaphane, tanshinone IIA, and tetramethylpyrazine in reducing inflammation and compare them with a known effective anti-inflammatory agent (interleukin-10 (IL-10)).

Methods

We searched relevant articles in Ovid database, Medline (PubMed) EMBASE, Google Scholar, Cochrane, and Scopus up to June 2013. The efficacy of each treatment and study powers were compared using random effects model of meta-analysis. To our knowledge, no conflict of interest exists.

Results

Eighteen articles entered into the study. The meta-analysis revealed that exogenous IL-10 was more effective in comparison with the mentioned herbal extracts. The proposed pathways for each medication''s effect on reducing the inflammation process are complex and many overlaps may exist.

Conclusion

IL-10 has a strong effect in the induction of neuroprotection and neurorecovery after SCI by multiple pathways. Tetramethylpyrazine has an acceptable influence in reducing inflammation through the up-regulation of IL-10. Outcomes of sulforaphane and tanshinone IIA administration are acceptable but still weaker than IL-10.     

Possible nitric oxide modulation in the protective effects of rutin against experimental head trauma–induced cognitive deficits: behavioral,biochemical, and molecular correlates

Background

Traumatic head injury is turning out to be a major cause of disability and death. Nitric oxide (NO), an intercellular messenger plays a crucial role in the pathophysiology of several neurologic disorders. Therefore, the present study was designed to investigate the effects of rutin, a well-known flavonoid against cognitive deficits and neuroinflammation associated with traumatic head injury and the probable role of NO pathway in this effect.

Materials and methods

Wistar rats were exposed to head trauma using weight drop method and kept for a postsurgical rehabilitation period of 2 wk. Later, animals were administered with rutin (20, 40, and 80 mg/kg; per oral) alone and in combination with NO modulators such as N^G-nitro-L-arginine methyl ester and L-arginine, daily for another 2 wk.

Results

Head injury caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Furthermore, there was a significant rise in acetylcholinesterase activity, oxidative stress, neuroinflammation (tumor necrosis factor α), and neuronal apoptosis (caspase-3) in both cortex and hippocampal regions of traumatized rat brain. Rutin significantly attenuated these behavioral, biochemical, and molecular alterations associated with head trauma. Furthermore, pretreatment of N^G-nitro-L-arginine methyl ester (10 mg/kg, intraperitoneally), a nonspecific nitric oxide synthase inhibitor, with subeffective dose of rutin (40 mg/kg) potentiated the protective effects; however, pretreatment of L-arginine (100 mg/kg; intraperitoneally), an NO donor, reversed the effects of rutin.

Conclusions

The present study suggests that NO modulation could possibly be involved in the neuroprotective effects of rutin against head trauma–induced cognitive deficits, neuroinflammation, and apoptotic signaling cascade.     

Effect of trimethylgallic acid esters against chronic stress-induced anxiety-like behavior and oxidative stress in mice

BackgroundMany studies have shown that the levels of oxidative stress (increased lipid peroxidation, decreased glutathione levels and endogenous antioxidant enzyme activities) and proinflammatory cytokines (e.g., TNF-α) are increased in patients with chronic fatigue syndrome. Gallic acid and other phenolic compounds are potent antioxidants and inhibitor of cytokine production. The present study was designed to investigate the effect of newly synthesized conjugated esters of trimethylgallic acid in an experimental model of chronic stress.MethodsThe animals were forced to swim individually for a period of 6 min every day for 15 days to induce chronic stress. The locomotor activity, anxiety-like behavior, and memory retention were evaluated in chronically stressed animals, followed by biochemical estimations and neuroinflammatory surge in the brain.ResultsChronic treatment with trimethylgallic acid esters for 15 days significantly reversed the chronic stress-induced behavioral (impaired locomotor activity, anxiety-like behavior, and decreased percentage of memory retention), biochemical (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities), and inflammation surge (serum TNF-α) in stressed mice.ConclusionsThe study revealed that trimethylgallic acid esters could ameliorate chronic stress-induced various behavioral and biochemical alterations in mice, showing protective effects against chronic stress.     

Chronic pain and neuroinflammation

In rheumatology, chronic pain most often sets in after a musculoskeletal injury. Its persistence is not always due to the progression of the initial injury, but in some cases to the onset of central sensitization. Much scientific data suggests that this central sensitization is caused by multiple complex interactions between the nervous system and immune system. Afferent nerve fibers carrying pain information are responsible for peripheral sensitization partly linked to inflammation molecules. These afferent fibers release neurotransmitters in the dorsal root ganglion and dorsal horn of the spinal cord, capable of activating microglia, which are the local immune cells. The activated microglia will produce pro-inflammatory cytokines, chemokines and neuropeptides capable of interacting with the second-order neuron, but also segmental and descending inhibitory neurons. This is referred to as neuroinflammation, which will amplify the hypersensitivity of second-order neurons, otherwise called central sensitization. This neuroinflammation will be able to reach the higher brain structures, which are involved in pain modulation and the emotional and cognitive aspects of pain. The aim of this update is to describe the pathophysiology of chronic pain, incorporating the latest scientific data on neuroplasticity and neuroinflammation.     

Full-length membrane-bound tumor necrosis factor-α acts through tumor necrosis factor receptor 2 to modify phenotype of sensory neurons

Neuropathic pain resulting from spinal hemisection or selective spinal nerve ligation is characterized by an increase in membrane-bound tumor necrosis factor-alpha (mTNFα) in spinal microglia without detectable release of soluble TNFα (sTNFα). In tissue culture, we showed that a full-length transmembrane cleavage-resistant TNFα (CRTNFα) construct can act through cell–cell contact to activate neighboring microglia. We undertook the current study to test the hypothesis that mTNFα expressed in microglia might also affect the phenotype of primary sensory afferents, by determining the effect of CRTNFα expressed from COS-7 cells on gene expression in primary dorsal root ganglia (DRG) neurons. Co-culture of DRG neurons with CRTNFα-expressing COS-7 cells resulted in a significant increase in the expression of voltage-gated sodium channel isoforms Na_V1.7 and Na_V1.8, and voltage-gated calcium channel subunit Ca_V3.2 at both mRNA and protein levels, and enhanced CCL2 expression and release from the DRG neurons. Exposure to sTNFα produced an increase only in CCL2 expression and release. Treatment of the cells with an siRNA against tumor necrosis factor receptor 2 (TNFR2) significantly reduced CRTNFα-induced gene expression changes in DRG neurons, whereas administration of CCR2 inhibitor had no significant effect on CRTNFα-induced increase in gene expression and CCL2 release in DRG neurons. Taken together, the results of this study suggest that mTNFα expressed in spinal microglia can facilitate pain signaling by up-regulating the expression of cation channels and CCL2 in DRG neurons in a TNFR2-dependent manner.     

Involvement of microRNAs in epileptogenesis

Patients who have sustained brain injury or had developmental brain lesions present a non‐negligible risk for developing delayed epilepsy. Finding therapeutic strategies to prevent development of epilepsy in at‐risk patients represents a crucial medical challenge. Noncoding microRNA molecules (miRNAs) are promising candidates in this area. Indeed, deregulation of diverse brain‐specific miRNAs has been observed in animal models of epilepsy as well as in patients with epilepsy, mostly in temporal lobe epilepsy (TLE). Herein we review deregulated miRNAs reported in epilepsy with potential roles in key molecular and cellular processes underlying epileptogenesis, namely neuroinflammation, cell proliferation and differentiation, migration, apoptosis, and synaptic remodeling. We provide an up‐to‐date listing of miRNAs altered in epileptogenesis and assess recent functional studies that have interrogated their role in epilepsy. Last, we discuss potential applications of these findings for the future development of disease‐modifying therapeutic strategies for antiepileptogenesis.     

CatacLysMic specificity when targeting myeloid cells?

The antibacterial enzyme lysozyme M (LysM) encoded by the Lyz2 gene is broadly expressed in myeloblasts, macrophages, and neutrophils, and thus has been used for a long time as a cell‐specific marker for myeloid cells in mice. In order to delete loxP‐site flanked genes in myeloid cells, a Cre‐recombinase (Cre) expressing mouse line was created by inserting Cre‐coding sequence into the translational start site of the LysM gene. In this issue of the European Journal of Immunology [2016. 46: 1529–1532], Orthgiess et al. verify, with the help of tdTomato and YFP reporter mouse lines, LysM‐driven recombination. Unexpectedly, the authors also describe major expression of the tdTomato reporter protein in brain neurons of the central nervous system (CNS), with only a very small percentage of gene recombination in myeloid cells of the brain, called microglia. These findings cause justified concerns regarding the efficient and specific targeting of microglia and peripheral myeloid cells using LysM‐Cre mice and should stimulate thoughts on conclusions drawn from past experiments on the diseased CNS employing this Cre/loxP‐deleter line.     

Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review

A growing body of evidence has shown that people with chronic low back pain (CLBP) demonstrate significantly greater declines in multiple cognitive domains than people who do not have CLBP. Given the high prevalence of CLBP in the ever-growing aging population that may be more vulnerable to cognitive decline, it is important to understand the mechanisms underlying the accelerated cognitive decline observed in this population, so that proper preventive or treatment approaches can be developed and implemented. The current scoping review summarizes what is known regarding the potential mechanisms underlying suboptimal cognitive performance and cognitive decline in people with CLBP and discusses future research directions. Five potential mechanisms were identified based on the findings from 34 included studies: (1) altered activity in the cortex and neural networks; (2) grey matter atrophy; (3) microglial activation and neuroinflammation; (4) comorbidities associated with CLBP; and (5) gut microbiota dysbiosis. Future studies should deepen the understanding of mechanisms underlying this association so that proper prevention and treatment strategies can be developed.     

Role of high mobility group box protein 1 in depression: A mechanistic and therapeutic perspective

As a common and serious psychiatric disorder, depression significantly affects psychosocial functioning and quality of life. However, the mechanism of depression is still enigmatic and perplexing, which limits its precise and effective therapeutic methods. Recent studies demonstrated that neuroinflammation activation plays an important role in the pathophysiology of depression. In this respect, high mobility group box 1 (HMGB1) may be a possible signaling inducer of neuroinflammation and can be a potential mechanistic and therapeutic target for depression. Herein, we review recent studies on the mechanistic and therapeutic targets of HMGB1 in depression and propose potential perspectives on this topic.