Toll-like receptor-4 antagonism mediates benefits during neuroinflammation

Neuroinflammation following immune activation in the central nervous system（CNS）leads to neuronal loss in specific areas of the CNS resulting in neurodegenerative disorders.Thus,fine tuning the immune responses within the brain is essential,because most of the brain diseases are associated with chronic inflammation,

Dimethyltryptamine(DMT):a biochemical Swiss Army knife in neuroinflammation and neuroprotection?

The inflammatory theory of many neuropsychiatric illnesses has become an emerging trend in modern medicine.Various immune mechanisms–mainly via the activity of microglia–may contribute to the etiology and symptomatology of diseases,such as schizophrenia,bipolar disorder,depression,or Alzheimer’s disease（Deleidi et al.,2015;Khandaker et al.,

A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits

Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1（PAR1）. However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004（3 mg/kg） 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.

State-of-art modelling of inflammatory astrocyte-synapse interactions in injury and amyotrophic lateral sclerosis

Different outcomes of astrocyte inflammatory signalling in injury and neurodegeneration：It is emerging that astrocytes have a significant impact on the neuronal network by modulating synaptic connections and neuronal viability in both normal and pathological states.

Oligodendrocyte ablation as a tool to study demyelinating diseases

Multiple sclerosis（MS） is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte（OL） loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.

Crocetin Potentiates Neurite Growth in Hippocampal Neurons and Facilitates Functional Recovery in Rats with Spinal Cord Injury

Crocetin is an ingredient of traditional Chinese medicine and has therapeutic potential in various diseases due to its pharmacological properties, such as neuroprotection, anti-oxidative stress, and anti-inflammation. These properties might benefit the treatment of spinal cord injury.In the present study, we tested the effect of crocetin on neurite growth and sensorimotor dysfunction in a rat model of spinal cord injury. We evaluated the viability of cultured hippocampal neurons with tetrazolium dye and lactate dehydrogenase assays, visualized neurites and axons with antibody staining, and monitored motor and sensorimotor functions in rats with spinal cord injury using the Basso,Beattie, and Bresnahan assay and the contact plantar placement test, respectively, and measured cytokine expression using enzyme-linked immuno-absorbent assays.We found that crocetin（1） did not alter the viability of cultured hippocampal neurons;（2） accelerated neurite growth with preference for the longest process in individual hippocampal neurons;（3） reversed the inhibition of neurite growth by chondroitin sulfate proteoglycan and Nogo A;（4） facilitated the recovery of motor and sensorimotor functions after spinal cord injury; and（5） did not inhibit pro-inflammatory responses, but restored the innervation of the descending 5-HT system in injured spinalcord. Crocetin promotes neurite growth and facilitates the recovery of motor and sensorimotor functions after spinal cord injury, likely through repairing neuronal connections.