Document Type: Research article
Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Department of Physiology, the Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Clinical Neurology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran.
Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran
Chronic cerebral hypoperfusion (CCH) leads to vascular dementia with progressive hippocampal damage and cognitive impairments. In the present study, we compared early and late treatment of Minocycline (MINO) on cognitive function, long and short-term synaptic-plasticity following CCH. We used bilateral common carotid arteries occlusion model (2VO) for induction of hypoperfusion. Male Sprague-Dawley rats were divided into 5 following groups (each having 2 subgroups): 2VO + V (vehicle), 2VO+MINO-E (early treatment of MINO on days 0 to 3 after 2VO), 2VO+MINO-L (late-treatment on days 21 to 32 after 2VO), control, and sham. Passive-avoidance (PA) and radial arm maze (RAM) tests were used to investigate learning and memory. Long term and short term synaptic plasticity were assessed by field potential recording, the brains were removed after recording and preserved for histological study to count pyramidal cells in CA1 region.
The CCH impaired memory performance, synaptic plasticity, and basal synaptic transmission (BST) along with hippocampal cell loss. Thus, the CCH rats exhibited a significantly reduction in step through latency (STL) of PA test with higher number of working and reference errors in RAM. However, only late treatment with MINO improved memory performance, synaptic plasticity, hippocampal cell loss and increased neurotransmitter pool (NP) in CCH rats, but early treatment could not produce long lasting beneficial effects 32 days after 2VO.
It is possible that MINO improve synaptic plasticity and memory performance in hypo-perfused rats directly and indirectly by increasing of NP and/or suppression of inflammatory factors respectively.