Targeting Neuroinflammation by Vascular Versus Metabolic Acting Drugs, in a Preventive or Therapeutic Approach, Using an Experimental Model of Sporadic Alzheimer’s Disease [sad].

Neuroinflammation, is a final consequence of neuro-vasculo-metabolic uncoupling, common to all major neurodegenerative disorders, as sAD. One cause is brain insulin resistance (BIR). Comparepreventive or therapeutic potentiality of vascular versus metabolic actingdrugs Their ability to suppress CSF neuroinflammatory markers, in STZ-induced, rat model of sAD. 63 rats were injected i.c.v. STZ (3mg/kg/10ul) to develop BIR that induces sAD, then grouped into: 21 as untreated-sampled on (7th/28th/90th) days / 28 as preventive-sampled after receiving oral dailysildenafil (10mg/kg), telmisartan (10mg/kg), rusovastatin (10mg/kg), orpioglitazone (10mg/kg) from 1st till 28th days / 14 astreated-sampled after receiving telmisartan or pioglitazone from 28thtill 90th days. Sampled CSF from cisterna magna was analyzed for IL-6,TNF-a, TGF-b, MDA, and p-tau. In untreated group; inflammatory markerswere detected on 7th while p-tau on 28th day. Theirsignificant elevation was more on 28th and 90th days respectively. By prevention; p-tau was not detected withany drug, while inflammatory markers were significantly reduced by telmisartanand pioglitazone > rusovastatin, tipping % reduction in favor of metabolicacting drugs. By treatment, % reduction in p-tau and neuroinflammation was moresignificant by telmisartan > pioglitazone, when compared to untreated group. Neuroinflammation was bettercontrolled in prevention by the collectively used metabolic than vascularacting drugs but the reverse was detected by those selected for treatment; denoting thatfinal outcomes are rather delineated by the drug's inherent ability to targetneuroinflammation, irrespective of its primary vascular versus metabolic action.