Injectable Inflammatory Response Hydrogel For The Treatment Of Alzheimer's Disease

Alzheimer's disease(AD)is a neurodegenerative disease that is related to aging and is characterized by decreased cognitive function and decreased learning and memory abilities.The main pathological features are the appearance of Senile Plaques(SPs)and neurofibrillary tangles(NFTs)in the brain.In recent years,with the deepening of research on the mechanism of neuroinflammation,it has been found that chronic inflammatory reaction in the brain has an important influence on the occurrence and development of AD.With current research methods,AD has not yet achieved a curative effect,and current treatment methods can only achieve remission levels and have high side effects.Existing studies have shown that a large amount of hyaluronic acid(HA)is degraded in the brain microenvironment,and the down-regulation of Neurogulin1(NRG1)expression is closely related to the occurrence and development of AD.Existing research has prepared an inflammation-responsive hydrogel TM-HA-NRG1,which shows good inflammatory responsiveness in the in vitro slow release ability and the inflammatory response that mimics the inflammatory environment,therefore,it has the research value as a treatment method for AD.In this paper,this inflammatory response hydrogel is injected into the bilateral lateral ventricles of AD model rats to explore whether it can respond to inflammation in the real inflammatory environment in the body,slow release and slow down the inflammatory reaction in the brain of mice,restore the cognitive,learning and memory impairment of AD model mice and achieve the therapeutic effect on AD.In this paper,the inflammatory response hydrogel TM-HA-NRG1 is injected into the lateral ventricle of APP/PS1 mice for sustained-release treatment of AD.By setting up controlled experiments,conduct behavioral testing experiments including: open field,new object recognition,water maze,etc.It was found that TM-HA-NRG1 has a good alleviating effect on APP/PS1 mice's learning cognition and the decline of spatial memory abili ty.In order to explore the internal mechanism of TM-HA-NRG1 antagonizing AD phenotype,we performed c-Fos/DAPI immunofluorescence staining on four groups of mice.A statistical analysis of the data revealed that the brain regions PFS,CA1,CA3,and DG played a role in the behavioral activities related to learning and memory.We observed that TM-HA-NRG1 can alleviate the occurrence and development of neuroinflammation by inhibiting the activation of microglia and the secretion of complement C1 q by immunofluorescence staining of microglial marker IBA1 and microglial activation marker CD68,and complement C1 q.Through SYP/PSD95 immunofluorescence staining,it was found that TM-HA-NRG1 has a certain promoting effect on the increase of synaptic plasticity.Throu gh C1q/PSD95 immunofluorescence staining,it was found that TM-HA-NRG1 can slow down the occurrence of intracranial inflammation by inhibiting the toxic effects of complement C1 q on synapses.In this paper,the intracranial intraventricular injection of TM-HA-NRG1 hydrogels showed good inflammatory responsiveness in the study of sustained release in vivo and simulated inflammatory environment.This indicates that the hydrogel has the functions of inhibiting inflammation and protecting nerves,thereby achieving antagonism and treatment of AD phenotype.