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Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):93-101. doi: 10.1016/j.pnpbp.2018.02.006. Epub 2018 Feb 10.

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

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna Street 12, Poland. Electronic address: domin@if-pan.krakow.pl.
2
Mossakowski Medical Research Centre, Polish Academy of Sciences, Department of Neurosurgery, Laboratory of Experimental Neurosurgery, A. Pawińskiego Street 5, 02-106 Warsaw, Poland. Electronic address: lprzykaza@imdik.pan.pl.
3
Mossakowski Medical Research Centre, Polish Academy of Sciences, Department of Neurosurgery, Laboratory of Experimental Neurosurgery, A. Pawińskiego Street 5, 02-106 Warsaw, Poland.
4
Laboratory of Animal Models, Neurobiology Centre, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
5
Institute of Pharmacology, Polish Academy of Sciences, Department of Neurobiology, 31-343 Kraków, Smętna Street 12, Poland.

Abstract

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.

KEYWORDS:

CatWalk; Neuroprotection; Open field test; Spontaneously hypertensive rats; Transient focal cerebral ischemia; Vibrissae-evoked forelimb-placing test

PMID:
29438731
DOI:
10.1016/j.pnpbp.2018.02.006
[Indexed for MEDLINE]

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