Moghe_2024_Int.J.Mol.Sci_25_7539

Reference

Title : scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate - Moghe_2024_Int.J.Mol.Sci_25_7539
Author(s) : Moghe M , Kim SS , Guan M , Rait A , Pirollo KF , Harford JB , Chang EH
Ref : Int J Mol Sci , 25 :7539 , 2024
Abstract :

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood-brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures.

PubMedSearch : Moghe_2024_Int.J.Mol.Sci_25_7539
PubMedID: 39062781

Related information

Reactivator 2-PAM

Citations formats

Moghe M, Kim SS, Guan M, Rait A, Pirollo KF, Harford JB, Chang EH (2024)
scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate
Int J Mol Sci 25 :7539

Moghe M, Kim SS, Guan M, Rait A, Pirollo KF, Harford JB, Chang EH (2024)
Int J Mol Sci 25 :7539