The hypothesis of the present study is that the anti-inflammatory property of
telmisartan (TM), an AT1 blocker that may exert neuroprotection through attenuation of
excitatory amino acids by controlling
cytokines and
reactive oxygen species, release during
ischemia. The
neuroprotective effect of TM and its combination with
nimodipine (NM) were studied in rats by using
middle cerebral artery occlusion method followed by ischemic reperfusion (IR) after 2 h of occlusion. The drugs were administered 30 min prior to the surgery and continued throughout the study period. After 24 h of IR the neurological deficit was assessed, and the locomotor activity and open field behaviour were assessed on the seventh day. On the ninth day, the brains were isolated for neurochemical and
cytokine measurements and histopathological studies. The results have shown that treatment of TM (5 & 10 mg/kg) gradually reduced the
glutamate,
aspartate and
glutamine synthetase levels. It also restored the
ATP, Na(+)K(+)
ATPase,
glutathione and synapse integrity in the different regions of the brain in comparison to ischemic brain. TM ameliorated the pro-inflammatory
cytokine (IL-1β, IL-6, TNF-α),
lipid peroxide and
nitric oxide levels. Anti-inflammatory
cytokine IL-10 level was found to be concurrently increased. Combination
therapy of TM with NM (5 mg/kg) has shown additive effects in the above said parameters. Further a positive correlation between
glutamate and
cytokine release was observed, and it indicated that synaptic clearance of
glutamate can be regulated by
cytokines. It can be concluded that TM induces neuroprotective activity through amelioration of pro-inflammatory
cytokine release during
cerebral ischemia. The additive effect of NM on TM
neuroprotective effect would be through controlling
cytokine release,
ATP restoration by cerebrovasodilation, and along with prevention of Ca(2+) dependent
glutamate toxicity in neurons. The advantage of TM
therapy in ischemic state can be explored clinically due to its dual effect in
hypertension.