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The model will likely need to be further optimized, and at the very least, the macaques treated with antiretroviral therapy for longer periods of time.
In macaques treated with minocycline during chronic infection, the second peak in MCP-1 levels in CSF was not observed [37].
Measurements of these markers in the frontal and parietal lobes of macaques treated with oral MN starting at 4 wpi revealed levels of SYN, MAP2 and neuronal counts that were not significantly different from uninfected CD8-depleted controls.
SIV-infected macaques treated with MVC (n = 6) were compared to a group of SIV-inoculated macaques (n = 22) and uninfected control macaques (n = 8) [17].
Although SIV increased CNS CCR5 expression, SIV-infected macaques treated with MVC had CCR5 RNA levels similar to uninfected control animals (Fig. 5c).
This finding is in sharp contrast with our findings in macaques treated with MVC monotherapy, further illustrating the potential value of CCR5 inhibition for lowering the latent HIV reservoir in the brain.
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Evidence supporting this approach includes the observation of neuronal injury reversal in this model, which occurred when macaques were treated with combination anti-retroviral drugs that did not penetrate the CNS [19].
Six SIV-infected rhesus macaques were treated with MVC monotherapy for 5 months beginning 24 days postinoculation; 22 SIV-infected animals served as untreated controls.
In this report, SIV-infected macaques were treated with MVC to evaluate the impact of CCR5 inhibition on SIV-induced CNS disease independent of other antiretroviral therapies.
Sections from basal ganglia region of macaques were treated with rabbit polyclonal PDGF-B antibody (Santa Cruz Biotechnology), followed by treatment with Alexa Fluor 594-conjugated anti-rabbit secondary antibody (1 : 500; Invitrogen) for 30 min at room temperature and mounted in Slow Fade anti-fade reagent with 4,6-diamidino-2-phenylindole (Molecular Probes, Eugene, OR, USA).
Experimental macaques were intramuscularly treated with Depo provera® (30 mg) 28 32 days prior to vaginal challenge with 300TCID50 of either virus which corresponded to 2.8×107 RNA copies/ml of SIVmac251 and 9.1×107 RNA copies of SHIVsf162p3 per inoculum.
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