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 (7^th/28^th/90^th) days / 28 as preventive-sampled after receiving oral dailysildenafil (10mg/kg), telmisartan (10mg/kg), rusovastatin (10mg/kg), orpioglitazone (10mg/kg) from 1^st till 28^th days / 14 astreated-sampled after receiving telmisartan or pioglitazone from 28^thtill 90^th 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 7^th while p-tau on 28^th day. Theirsignificant elevation was more on 28^th and 90^th 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.