HMGB1 Review: The role of HMGB1 in the persistence of epilepsy in juvenile rats

Clinical HMGB1

Epilepsy is one of the most common chronic diseases of the nervous system. The long-term recurrent epileptic seizures have a high incidence of disease in children. Long-term, frequent or severe epileptic seizures can lead to further brain damage or even persistent Neuropsychiatric disorders, to the patient himself and the family, the community caused great distress. In recent years, the research on the etiology, pathogenesis and treatment of epilepsy has made great progress, but the exact mechanism of epilepsy development and development has not been fully elucidated. A large number of studies have shown that epilepsy persistence, brain trauma and ischemia and hypoxia and other brain damage processes are accompanied by immune response to the nervous system, and the immune system of the immune system can increase neuronal excitability, promote neuronal damage and epilepsy. Numerous studies have shown that a variety of inflammatory mediators are involved in the development and progression of epilepsy, and antiinflammatory therapy is effective for some types of seizures that can reduce the degree of attack and neuropathological changes. High-mobility group box 1 (HMGB1) is a highly conserved non-DNA binding protein with stable nucleic acid structure, regulation of transcription and gene expression and other biological functions. In recent years, it has been found that HMGB1 can be released by necrotic cells or released by activated immune cells, and by their receptors such as Toll-like receptor (toll-like receptor) (TLR2), Toll-like receptor 2 (TLR2) and advanced receptor-advanced glycation end products (RAGE), and activate nuclear factor-NF- kB and other signaling pathways to promote the production of inflammatory factors and chemokines, and thus play its proinflammatory effect. TLR is an innate receptor, which is one of the most important receptors in the study of TLR4, which is one of the most important receptors in the study. It is one of the most important receptors in the study. The nervous system, including neurons, microglia and astrocytes, is involved in a variety of neurological disorders. The study confirmed HMGB1 involved in sepsis, arthritis, pancreatitis, respiratory disorders, cerebral ischemia, brain trauma, encephalitis and other pathological processes. The HMGB1 inhibitors, such as neutralizing antibodies, Box A, can alleviate the inflammatory response caused by HMGB1 in a variety of diseases and play a protective role. On the contrary, recombinant HMGB1 can aggravate the inflammatory response and tissue damage. For example, HMGB1 neutralizing antibody in sepsis can reduce the inflammatory response and reduce mortality; HMGB1 translocation activation in cerebral ischemia and traumatic brain injury, HMGB1 neutralizing antibody can inhibit HMGB1 activation and inflammatory response, reduce brain Injury, and given recombinant HMGB1 can increase cytokine synthesis, promote glial cell activation and increase neuronal damage. Recent studies have shown that HMGB1 / TLR4 signaling pathways are involved in the development of adult mice with epilepsy, and plasma HMGB1 levels are also observed in children with febrile seizures. However, whether HMGB1 is involved in seizures of minors and whether HMGB1 neutralizing antibodies have neuroprotective effects in seizures is still unclear. Studies have shown that epilepsy susceptibility, neuropathological changes and prognosis are age-dependent, And the expression of HMGB1 is also affected by age, so in this subject, we through the lateral ventricle injection of kainic acid (kainic acid, KA) 21 days after birth (postnatal day21, P21) rat epilepsy status ( (HMh1 / TLR4) pathway in hippocampus and the characteristics of neuronal injury in the early stage of SE (3h-7d), and the HMGB1 neutralizing antibody was used to block HMGB1 activity. And the expression of HMGB1 on the status of hippocampal inflammatory factors, the activation of glial cells and the damage of neurons in epileptic seizures.

Reference

Zeng J-C, Xiang W-Y, Lin D-Z, et al. Elevated HMGB1-related interleukin-6 is associated with dynamic responses of monocytes in patients with active pulmonary tuberculosis. International Journal of Clinical and Experimental Pathology. 2015;8(2):1341-1353.

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