BMSCs transplantation improves cognitive impairment via up-regulation of hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion

Parvalbumin and Neuropeptide Y Neuronal Loss in the Hippocampal CA1 Subarea is Associated with Cognitive Deficits in a Rat Model of Chronic Cerebral Hypoperfusion

“…We did observe significant GABAergic cell loss in the hippocampal CA1 subarea in CCH. Apart from this, the population of GABA-and GAD67-positive cells in hippocampal CA1 subarea also significantly declines during CCH according to our previous findings [9]. These findings may reflect the selectively impaired GABAergic function in hippocampal CA1 subarea.…”

“…Although differences in the brain vulnerability to ischemia are observed in most strains of BCCAO models, a similar pattern of selective hippocampal CA1 neuronal loss has been found [10,11,32]. The severity of hippocampal neuronal loss in the BCCAO models may be different in terms of animals (such as rat, mouse and gerbil) [9,32], time of occlusion [12,33], etc. Furthermore, significant cell loss of hippocampal GABAergic interneurons has been reported in the neurodegenerative diseases as well, such as AD and aging [34,35].…”

“…BCCAO is so far a common paradigm of experimental models of VaD and AD [2,6,7], and can induce diffuse white matter lesions, hippocampal neuronal cell loss, micro-infarcts and micro-hemorrhages, as well as obvious cognitive impairments such as spatial learning and memory deficits [1,6]. Generally, hippocampus is responsible of spatial learning and memory processes, specifically, neuronal damage caused by BCCAO in the hippocampus is restricted to CA1 subarea [8,9], and some studies further discovered that performance of spatial learning shows a significant correlation with the numbers of neurons in the CA1 area [10,11]. Taken together, the neuronal damage in hippocampal CA1 subarea of BCCAO rats is closely related to the spatial learning and memory impairments.…”

“…Numerous studies have found that gamma amino butyric acid (GABA)ergic interneurons in hippocampus play an essential role in the regulation of cognitive ability, and marked GABAergic cell loss and decreased GABA neurotransmission in the hippocampal subareas result in cognitive deficits in AD and VaD [9,[12][13][14][15]. However, the alteration of GABAergic interneurons in the hippocampus has not been clearly identified in CCH so far, even though other pathological changes including neuronal damage, glial activation and oxidative stress have been already reported [6,10,16].…”

“…The experiment consisted of a four-day hidden platform test and a one-day single probe test. The procedure was described as previous report [9]. Briefly, the rats were released to the water from a randomized quadrant after training to search for the hidden platform.…”