Our previous studies have shown that
ACPT-I [(1S, 3R,4S)-1-aminocyclopentane-1,2,4-
tricarboxylic acid], a blood-brain barrier permeable agonist of group III metabotropic
glutamate (mGlu) receptors, was neuroprotective against
middle cerebral artery occlusion/reperfusion (MCAO/R) in normotensive rats. Preclinical studies are typically performed on healthy animals, whereas
stroke patients predominately exhibit comorbidities, such as
hypertension; therefore, in the present study, we investigated the effect of
ACPT-I in spontaneously hypertensive rats (SHR) after MCAO/R. We examined the potential neuroprotective action of
ACPT-I (30 mg/kg) when administered during occlusion or reperfusion via the assessment of not only the
brain infarction volume but also motor (CatWalk gait analysis and open field test) and sensorimotor (vibrissae-evoked forelimb-placing test) functions following MCAO/R. We determined that
ACPT-I not only reduced the cortico-striatal
infarction but also improved several gait parameters (run speed, run and stand durations, swing speed and stride length) and mobility when administered 30 min after the start of the occlusion or 30 min after the start of reperfusion. Moreover, the sensorimotor function was improved in hypertensive rats treated with
ACPT-I during occlusion. In conclusion, the current findings provide further evidence for the
neuroprotective effects of
ACPT-I against ischemic damage. These findings may have clinical implications because
hypertension is an important risk factor for
ischemic stroke.