Author(s): Santos, Sónia Sá ; Santos, Sara M. ; Pinto, Antónia R. T. ; Ramu, Vasanthakumar G. ; Heras, Montserrat ; Bardaji, Eduard ; Tavares, Isaura ; Castanho, Miguel A. R. B.
Date: 2016
Persistent ID: http://hdl.handle.net/10451/32813
Origin: Repositório da Universidade de Lisboa
Subject(s): 2VO-dementia model; Chronic cerebral hypoperfusion; Cognitive impairment; Hippocampus; Kyotorphin derivatives; Neuroprotection
Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.
