Minocycline, a 2nd generation tetracycline derivative, is reported by several to possess anti inflammatory properties both in vitro and in vivo. In an amyloid beta injected rat model, minocycline has shown to effectively reverse the activation of glial cells. In our new examine, minocycline also proficiently inhibited gp120 mediated upregulation of various inflammatory markers from the frontal cortex, hippocampus and striatum and further prevented secretion of cytokines inside the CSF. Lately, minocycline has been examined within a clinical trial in HIV infected individuals with cognitive impairment. Al even though this study reported that minocycline treatment was unsuccessful in bettering neurocognitive perform in individuals with cognitive impairment, it really is even now incon clusive if administration from the drug at earlier stages with the infection could have a superior clinical end result.
Considering that min ocycline has been reported to possess a safe and sound profile when administered with antiretroviral medicines in HIV infected in dividuals, it will be crucial to assess if early administra tion of antiretroviral medicines in addition to minocycline has any advantageous effects against HIV connected neurocognitive ailments. Numerous clinical studies indicate earlier adminis tration of antiretroviral drugs can lessen the incidence of neurological issues. In a SIV model, early ad ministration of minocycline was reported to become helpful against striatal dopaminergic program dysfunction, recommend ing that timely therapy initiation could have an effect on minocycline efficacy.
Since antiretroviral drugs don't have anti inflammatory properties, a mixture treatment together with antiretroviral and anti inflammatory compounds could protect against the devel opment of HIV connected cognitive deficits. We also tested chloroquine, an antimalarial drug which exhibits anti inflammatory and anti HIV effects in vitro and in vivo. For example, chloroquine administration has become reported to reduce T cell activation in continual HIV contaminated patients. In the rodent model, chloroquine pre vented a bacterial toxin induced intracerebral toxicity. In our gp120 administered model, chloroquine was able to suppress IL 1B and iNOS mRNA ranges during the frontal cor tex, hippocampus and striatum. Chloroquine was also ef fective in reversing gp120 mediated IL 1B release in the CSF. Nevertheless, chloroquine was not in a position to inhibit gp120 mediated release of TNF. Clinical trials are important to figure out no matter if chloroquine may very well be advantageous in re ducing HIV related cognitive impairments, specifically in populations where malaria is additionally prevalent. Simvastatin, an HMG CoA reductase inhibitor, is another compound which has demonstrated anti inflammatory properties and neuroprotective results.