Effect of a Rho Kinase Inhibitor on Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Abstract

We examined the efficacy of a Rho kinase inhibitor, Fasudil, on cognitive impairment induced by chronic cerebral hypoperfusion in rats. Thirty-two male adult Sprague-Dawley rats were randomly divided into three groups; treated (T), control (C), and sham-operated (Sh); severe stenosis of the carotid arteries was modeled in the former two groups. During two weeks, 8.35 mg/kg Fasudil and physiological saline were i.p. applied twice per day in the T and C groups, respectively. The Morris water maze test was performed in each group to detect changes in the cognitive function and to observe pathological shifts in hippocampal morphology in rats after eight weeks. The mean escape latency was distinctly shorter (P < 0.01), and the percentage of swimming distance within the platform quadrant was significantly greater (P < 0.01) in the T group, compared to those in the C group at the corresponding time points. The rate of carotid artery stenosis in rats demonstrated no statistical difference between the T and C groups (P > 0.05). Fasudil injections effectively normalized hippocampal pathomorphology in the T group. Thus, the Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats.

Combination of isoflurane and propofol as general anaesthesia during orthopaedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anaesthesia during perioperative cerebral hypoperfusion

“…If the increased expression of BiP is su cient to bind unfolded/misfolded proteins, then ER stress could be alleviated and the neuron could adapt, as observed for Group IP 1 in this study. Otherwise, prolonged or excess expression of CHOP will lead to apoptosis [44], as observed for Groups I, P and IP 2 .…”

“…In our study, a ligation of bilateral CCA surgery [44] was adopted to prepare rats as CH animal model [45]. A second surgery, ORIF [46], requiring general anaesthesia, was operated 30 days later so that the effects of anaesthetics on cognitive function of these CH rats could be assessed.…”

“…The wound was sutured and disinfected. During surgery, a heating lamp was used to help maintain the body temperature of anaesthetized rats at 37 ± 0.5°C [44].…”

Combination of isoflurane and propofol, a means for general anesthesia in the orthopedic surgery of perioperative cerebral hypoperfusion rats to avoid cognitive impairment Anesthesia of perioperative cerebral hypoperfusion

“…If the increased expression of BiP is sufficient to bind unfolded/misfolded proteins, then ER stress could be alleviated and the neuron could adapt. If not, prolonged or excess expression of CHOP will lead to apoptosis [34].…”

“…In our study, a ligation of bilateral CCA (common carotid arteries) surgery [34] was adopted to prepare rats as CH animal model [35]. A second surgery, open reduction and internal fixation (ORIF) [36], requiring general anesthesia, was operated so that the effects of anesthetics on cognitive function of these CH rats could be assessed.…”