Mohammad Khajenouri , Masoud Fereidoni ,
Volume 27, Issue 4 (12-2025)
Abstract
Background and Objective: Stroke is considered one of the leading causes of mortality and disability worldwide. Excitotoxicity, neuroinflammation, and oxidative/nitrosative stress resulting from cerebral ischemia/reperfusion lead to cell death, cerebral edema, and cognitive-behavioral impairments, such as deficits in short-term and long-term memory. This study was conducted to determine the effect of minocycline on behavioral-cognitive impairments induced by global cerebral ischemia.
Methods: This experimental study was conducted on 56 male Wistar rats (weighing 220–280 g) at Ferdowsi University of Mashhad, Iran. The animals were randomly assigned to the following groups: Control, solvent, surgery, surgery + solvent + ischemia/reperfusion, surgery + ischemia/reperfusion, and minocycline-treated groups (administered intraperitoneally at doses of 11.25, 22.50, and 45 mg/kg/bw). At specified intervals following the surgical induction of global cerebral ischemia/reperfusion, a surgery procedure and a carotid artery occlusion method were employed for 20 minutes. Following a 30-minute interval post-procedure, the drug or solvent was injected intraperitoneally on day 0. These injections continued for seven consecutive days at a fixed time each day. On day 7, anxiety-like behavior was assessed using the open-field test. Subsequently, the Y-maze test was utilized to evaluate short-term memory, while the Morris water maze (MWM) test was employed to assess spatial long-term memory and reversal memory in the following days.
Results: In the Y-maze test, ischemia culminated in a 33% decrease in short-term memory performance (P<0.05). Minocycline at doses of 22.50 and 45 mg/kg/bw improved short-term memory by 20% and 25% compared to the ischemia group, respectively (P<0.05). In the open-field test, ischemia caused a 66% decrease in time spent in the center of the field, indicating increased anxiety (P<0.05). Minocycline at a dose of 45 mg/kg/bw reduced anxiety by 32% compared to the ischemia group (P<0.05). In the MWM test, ischemia significantly increased the time to find the platform on days 2 and 4 (P<0.05). Minocycline at doses of 22.50 and 45 mg/kg/bw significantly decreased the time to find the platform (P<0.05). In the reversal phase of the MWM test, ischemia led to a decline in long-term memory performance (P<0.05), while minocycline at doses of 11.25, 22.50, and 45 mg/kg/bw significantly improved performance (P<0.05). In the probe trials, ischemia reduced the time spent in the target quadrant by 54% in probe 1 and 47% in probe 2 (P<0.05). Minocycline at 45 mg/kg/bw increased the time spent in the target quadrant by 45% in probe 1 and 34% in probe 2 (P<0.05). No statistically significant changes in motor activity were observed between the groups.
Conclusion: Minocycline, particularly at doses of 22.50 and 45 mg/kg, significantly improves cognitive function, memory, and anxiety without inducing motor activity impairments following cerebral ischemia.
