Neuroprotective effect of the group III mGlu receptor agonist ACPT-I after ischemic stroke in rats with essential hypertension

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 84; no. Pt A; pp. 93 - 101
• Main Authors: Domin, Helena, Przykaza, Łukasz, Kozniewska, Ewa, Boguszewski, Paweł M., Śmiałowska, Maria
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 08.06.2018
• Subjects: Animals; Brain - drug effects; Brain - pathology; Brain Ischemia - complications; Brain Ischemia - drug therapy; Brain Ischemia - pathology; CatWalk; Cyclopentanes - pharmacology; Essential Hypertension - complications; Essential Hypertension - drug therapy; Essential Hypertension - pathology; Gait - drug effects; Male; Neuroprotection; Neuroprotective Agents - pharmacology; Open field test; Random Allocation; Rats, Inbred SHR; Receptors, Metabotropic Glutamate - agonists; Sensation - drug effects; Spontaneously hypertensive rats; Stroke - complications; Stroke - drug therapy; Stroke - pathology; Transient focal cerebral ischemia; Tricarboxylic Acids - pharmacology; Vibrissae-evoked forelimb-placing test; Neuroprotection; Spontaneously hypertensive rats; Transient focal cerebral ischemia; Open field test; CatWalk; Vibrissae-evoked forelimb-placing test
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2018.02.006

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. •ACPT-I is neuroprotective against ischemic brain damage in hypertensive rats.•ACPT-I improves the post-ischemic locomotor activity in hypertensive rats.•ACPT-I improves the post-ischemic gait after delayed treatment in hypertensive rats.•ACPT-I decreases sensorimotor perturbations after MCAO in hypertensive rats.