The pathogenesis of autism spectrum disorder (ASD) likely involves genetic and environmental factors, impacting the complex neurodevelopmental and behavioral abnormalities of the disorder. Scientific research studies emerging within the past two decades suggest that immune dysfunction and inflammation have pathogenic influences through different mechanisms, all leading to both a chronic state of low grade inflammation, and alterations in the central nervous system and immune response, respectively. The high mobility group box-1 protein (HMGB1) is an inflammatory marker which has been shown to play a role in inducing and influencing neuroinflammation. Current evidences suggest a possible role in the multiple pathogenic mechanisms of ASD. The aim of this manuscript is to review the major hypothesis for ASD pathogenesis, with specific regards to the immunological ones, and to provide a comprehensive review of the current data about the association between HMGB1 and ASD. A systematic search has been carried out through Medline via Pubmed to identify all original articles published in English, on the basis of the following key word “HMGB1”, “autism”, “autism spectrum disorder”, “neuroinflammation”, and “child”.

Introduction: neuroinflammation is a primary pathophysiological condition that is associated with cognitive impairment and neurodegenerative diseases. The present study was designed to evaluate the effects of enriched environment (EE) on passive avoidance (PA) memory impairment caused by lipopolysaccharide (LPS) induced neuroinflammation. Methods: Twenty-eight male Wistar rats were assigned into the following groups: 1, control; 2, control+ EE; 3, LPS and 4, LPS+ EE. LPS injection (1mg/kg/i. p. ) was done on days 1, 3, 5 and 7 of experiment. Two different housing conditions were used in this experiment, including a standard environment house and an enriched environment house. The passive avoidance task was used to examine animals learning and memory performance. The hippocampal level of interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) was also measured using sandwich-ELISA method. Results: Obtained data indicated that LPS significantly impaired passive avoidance memory, decreased the step-through latency and increased the time spent in the dark compartment of the LPS treated group compared to the control group. On the other hand, EE housing could significantly ameliorate memory impairment. Hippocampal IL-6 level was increased and BDNF was decreased in the LPS group, whereas EE could decrease and increase IL-6 and BDNF levels in the LPS+EE group, respectively. Conclusion: EE should probably be considered as an alternative strategy in neuroinflammatory diseases to minimize the memory impairment.