Animals ; Apoptosis ; Humans ; Ischemia ; pathology ; Neurons ; pathology ; Signal Transduction ; physiology

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Humans ; Astrocytes/pathology* ; Chronic Pain/pathology* ; Neuroglia/physiology* ; Neurons/physiology* ; Synaptic Transmission ; Chronic Disease

Animals ; Electric Stimulation ; Neurons ; pathology ; physiology ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Red Nucleus ; pathology ; physiology

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

In the vertebrate retina, Müller cells are principal glial cells which stretch across the whole thickness of the retina and contact with the somata and processes of all retinal neurons, thus forming an anatomical and functional link between glial cells and retinal neurons. Numerous studies have shown that Müller cells express various neurotransmitter receptors, transporters, ion channels and enzymes that are relative to cellular activities. In addition, the cells also release factors, such as D-serine and glutamate etc., to regulate the neuron excitability. Therefore, retinal Müller cells may play more curious roles in addition to supporting the retinal neurons. The information exchange and interaction between Müller cells and neurons may regulate and maintain retinal neuronal functions. In the glaucomatous retina, Müller cells are reactivated (gliosis). Reactivated Müller cells undergo a variety of changes in cellular physiology, biochemistry and morphological features. Meanwhile, the reactivated Müller cells may produce and release cytotoxic factors, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and prostaglandin E2 (PGE2), thus involving in the induction of retinal ganglion cell apoptosis and death. Here, we reviewed the physiological properties of retinal Müller cells, and the functional changes of Müller cells in the glaucomatous retina.
Ependymoglial Cells ; pathology ; physiology ; Glaucoma ; physiopathology ; Humans ; Neurons ; physiology ; Retina ; cytology

The brain-gut peptide ghrelin, a endogenous ligand for the growth hormone secretagogue hormone receptor, is mainly produced by gastric cells in the periphery, regulating energy metabolism via stimulating the appetite. Inside the brain, ghrelin is mainly expressed in the pituitary and in the hypothalamic arcuate nucleus, regulating the synthesis and secretion of neuropeptides that are correlated with feeding behavior, reproduction, and stress responses. Recently, more and more researches focused on the regulating roles of ghrelin on learning and memory, and mood regulation have indicated that ghrelin may inhibit neuronal apoptosis, improve cognitive function, and regulate the activities of neuroendocrine systems such as the hypothalamo-pituitary-adrenal axis and the hypothalamo-pituitary-gonadal axis thus get involved in the pathogenesis of neuropsychiatric diseases. The aim of this review is to summarize the main findings in this field, with the purpose of promoting further studies on the role of ghrelin in the brain.
Apoptosis ; Brain ; metabolism ; pathology ; physiology ; Ghrelin ; metabolism ; physiology ; Humans ; Learning ; Memory ; Neurons ; pathology ; Parkinson Disease ; metabolism ; pathology ; physiopathology

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.
Acetylcholine ; physiology ; Basal Forebrain ; pathology ; Brain Chemistry ; genetics ; physiology ; Cholinergic Neurons ; chemistry ; classification ; pathology ; physiology ; Epilepsy ; genetics ; pathology ; physiopathology ; Epilepsy, Frontal Lobe ; genetics ; GABAergic Neurons ; physiology ; Hippocampus ; pathology ; Humans ; Mutation ; genetics ; physiology ; Neurons ; Non-Neuronal Cholinergic System ; genetics ; physiology ; Receptors, Muscarinic ; genetics ; physiology ; Receptors, Nicotinic ; genetics ; physiology ; Synaptic Transmission ; genetics ; physiology

The evidence and the feature of apoptosis following tyrauma brain injury(TBI) and the possible mechanisms underlying apoptosis were reviewed. Recently research showed that apoptosis play an important role in TBI, the occurring time and area of apoptosis were found significant differences compared with that of necrosis. The neural cell apoptosis can undergo following many pathways after TBI. In our review, the foreground of apoptosis after TBI research in forensic pathology were also discussed.
Animals ; Apoptosis/physiology* ; Brain Injuries/pathology* ; Forensic Medicine ; Gene Expression Regulation ; Humans ; Neurons/pathology*

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. Although many problems and challenges remain, the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat SCI. In this review, we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following SCI at both the acute and chronic stages. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. Finally, we consider the future of SCI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical practice. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI.
Humans ; Axons/pathology* ; Nerve Regeneration/physiology* ; Spinal Cord Injuries/therapy* ; Neurons/pathology* ; Recovery of Function

The participation of activated leukocytes and subsequent production of chemical mediators has been well accepted in the pathophysiology of hypoxic-ischemic injury. This study was performed to see the effects of leukocytes on hippocampal neuronal damage in transient global ischemia induced by 10-min occlusion of bilateral common carotid arteries (CCAs) with reperfusion for various times, and in complete unilateral ischemia induced by 24-hr ligation of left CCA. Leukopenia was induced by intraperitoneal injection of cyclophosphamide for 4 days. The results showed that hippocampal neuronal damages were worse at 6-hr reperfusion in leukopenic experimental group than in the control group. In comparison, 24-hr and 3-day reperfusion leukopenic groups showed less numbers of damaged neurons and milder changes. The 5-day reperfusion group showed inconsistent changes. Unilateral CCA occlusion showed extensive infarction in 83.3% of gerbils in the control group, compared to 25% of gerbils in the experimental group (p<0.05). These results strongly suggest that the number of peripheral leukocytes were closely related to the development of delayed neuronal damage of hippocampus in transient global ischemia and the incidence of infarction induced by 24-hr unilateral CCA ligation.
Animal ; Cerebral Infarction/pathology* ; Female ; Gerbillinae ; Hippocampus/pathology* ; Leukocyte Count ; Leukocytes/physiology* ; Male ; Neurons/pathology* ; Reperfusion Injury