A Heatmap of differential genes, C differential gene volcano plot, E KEGG circle diagram of differential genes in MAKP pathway between the rmTBI and sham groups. All differentially expressed genes between the MPC-ngroup and the rmTBI group. Vitamin A 12916_2023_2895_MOESM5_ESM.xlsx (61K) GUID:?78B561C9-432D-4A7E-8841-3FA7FBC84DDC Additional file 6.?Original uncropped Western blots of GAPDH 1. 12916_2023_2895_MOESM6_ESM.tif (596K) GUID:?3F3DA008-6EB9-40F0-926E-83579D46F7BD Additional file 7.?Original uncropped Western blots of GAPDH 2. 12916_2023_2895_MOESM7_ESM.tif (3.5M) Vitamin A GUID:?563E1F36-D170-4963-943B-93EBF3438D23 Additional file 8.?Original uncropped Western blots of p-Tau. 12916_2023_2895_MOESM8_ESM.tif (3.5M) GUID:?F6ABC663-5491-44FF-817E-142A789B6445 Additional file 9.?Original uncropped Western blots of p-p38 MAPK. 12916_2023_2895_MOESM9_ESM.tif (3.5M) GUID:?E6D4D78C-3B70-4E73-BDC1-62F5F901B9D2 Data Availability StatementThe data that support the findings of this study are available from the corresponding author upon reasonable request. Abstract Background Contact sports athletes and military personnel who suffered a repetitive mild traumatic brain injury (rmTBI) are at high risk of neurodegenerative diseases such as advanced dementia and chronic traumatic encephalopathy (CTE). However, due to the lack of specific biological indicators in clinical practice, the analysis and treatment of rmTBI are quite limited. Methods We used 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules to deliver immunoglobulins (IgG), which can increase the delivery effectiveness and specific target of IgG while reducing the effective restorative dose of the drug. Results Our results shown that MPC-capsuled immunoglobulins (MPC-n (IgG)) significantly alleviated cognitive impairment, hippocampal atrophy, p-Tau deposition, and myelin injury in rmTBI mice compared with free IgG. Furthermore, MPC-n (IgG) can also efficiently inhibit the activation of microglia and the launch of inflammatory factors. Conclusions In the present study, we put forward an efficient strategy for the treatment of rmTBI-related cognitive impairment and provide evidence for the administration of low-dose IgG. Supplementary Info The online version contains supplementary material available at 10.1186/s12916-023-02895-7. Keywords: Repeated mild traumatic mind injury, Immunoglobulin, Cognitive impairment, Neuro-inflammation Background Traumatic mind injury (TBI) is definitely a common and severe neurological disease, which contributes to approximately $400 billion yearly [1]. The number of fresh TBI individuals is as high as 50 million to 60 million each year, and 80C90% of them are slight TBI (mTBI) [2, 3]. In particular, repetitive mild traumatic mind injury (rmTBI) can contribute to chronic traumatic encephalopathy (CTE) due to the continuous accumulation of damage. CTE is mainly characterized by phosphorylated-Tau (p-Tau) deposition, microglial activation, and white matter rarefaction [4C6]. The highest incidence of rmTBI individuals are among contact sports athletes, armed service veterans, and elderly people who have fallen over the years [4, 7]. Because of the slight symptoms and the late onset, the discussion rate of rmTBI is definitely low and the treatment is always delayed. Immunoglobulin (IgG) is definitely a polyclonal product purified from human being serum and has been used as an Vitamin A effective first-line drug for numerous neurological diseases, such as Guillain Barre syndrome, chronic inflammatory Vitamin A demyelinating polyneuropathy, and multifocal engine neuropathy [8]. Since IgG can directly target the immune system and neurons, IgG has also demonstrated a potential in the Tagln treatment of ischemic stroke [9, 10]. In addition, in preclinical and medical trials of slight to moderate Alzheimers disease (AD), IgG was reported to efficiently reduce amyloidosis (A) and modulated the neuroimmune response, as well as remit mind atrophy in individuals [11, 12]. In a study of closed cranial stress, high doses of IgG (600?mg/kg) were shown benefits in improving behavioral and cognitive function in mice with a single impact [13]. However, high dose use of IgG was limited considering security and feasibility. Many clinical tests have found that individuals treated with high-dosage IgG tend to suffer side effects, such as thrombosis and anaphylaxis [8, 14]. In recent years, nanocapsules were used to improve the delivery effectiveness and reduce the effective restorative dose of medicines because of the superb biocompatibility and bloodCbrain barrier (BBB) permeability [15]. We have previously shown that 2-methacryloyloxyethyl phosphorylcholine (MPC) synthesized with the MPC monomer and ethylene glycol dimethyl acrylate (EGDMA) crosslinker, like a choline and acetylcholine analog, can be taken up and transferred by high-affinity choline transporter (ChTs) receptors of endothelial cells from your blood into the mind parenchyma [16]. Although IgG has been extensively analyzed in a variety of neurological disorders, its effectiveness in cognitive impairment in rmTBI has been hardly ever analyzed. In the present study, MPC-capsuled IgG (MPC-n (IgG)) was used to treat long-term cognitive impairment in rmTBI mice. We 1st demonstrated the specific build up of MPC-n (IgG) in the cortex and hippocampus of rmTBI mice, which confirmed that MPC-n (IgG) improved the BBB penetration and drug delivery effectiveness. Next, we identified p-Tau deposition, hippocampal atrophy, cognitive function, and microglial activation in rmTBI mice during the chronic phase. Our study shows that MPC-n (IgG) can efficiently ameliorate cognitive dysfunction and neuroinflammation in rmTBI mice, which provides a potential strategy for the application with a low dose.