Pharmacological studies of a novel prolyl endopeptidase inhibitor, JTP-4819, in rats with middle cerebral artery occlusion

Watermaze Performance after Middle Cerebral Artery Occlusion in the Rat: The Role of Sensorimotor versus Memory Impairments

“…Consistent with previous studies, MCAO resulted in an increased escape latency and path length relative to sham and unoperated animals in a watermaze spatial reference-memory task (Markgraf et al, 1992;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Wang et al, 2010;Xu et al, 2009;Yonemori et al, 1996;Yun et al, 2007;Zhang et al, 2010). However, from close scrutiny of the behavior of MCAO animals in the watermaze, the present study indicates that maintained focal ischemia within the MCA territory has little effect on the acquisition and retention of spatial reference memory.…”

“…A number of watermaze studies have been performed to determine the effect of MCAO on learning and memory deficits using either the Tamura model of permanent MCAO by electrocoagulation (e.g., Markgraf et al, 1992;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Yonemori et al, 1996) or the intraluminal thread model (e.g., Hayase et al, 2009;Kawanishi et al, 2010;Noh et al, 2011;Xu et al, 2009;Yun et al, 2007). It is important to note that with intraluminal thread models, particularly in mice, filament insertion can lead to loss of blood supply to the hippocampus (McColl et al, 2004), therefore although intraluminal thread is used as a model of MCAO, it is in fact capable of producing more widespread ischemia affecting other major blood vessel territories.…”

“…However, a neurologic test battery revealed sensorimotor impairments such as abnormal posture and hemiparesis at the time of watermaze testing. During watermaze acquisition after MCAO, an increased latency to reach the platform (Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996) or an increased latency plus an increased path length (Smith et al, 1997;Markgraf et al, 1992;Yonemori et al, 1999) have been observed as evidence of memory deficits. Smith et al (1997) and Yonemori et al (1999) showed extensive thigmotactic swimming in the MCAO group compared with the sham group.…”

“…Group 1 underwent a proximal permanent left MCAO (n = 10). A standard model of MCAO (the electrocoagulation Tamura model; Tamura et al, 1981) used in previous watermaze studies (Markgraf et al, 1992;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Yonemori et al, 1996) was adopted where ischemia encompasses frontal, parietal, and perirhinal cortices and striatum, as described previously (Bingham et al, 2005). Anesthesia was induced with 5% halothane and the animals were then mechanically ventilated and anesthesia maintained with 1% to 2% halothane in 100% oxygen.…”

“…Understanding these functional deficits is essential for development of future therapies. Many experimental studies have used watermaze tasks to better understand spatial learning and memory deficits after MCA occlusion (MCAO) and to assess potential future therapies (Hayase et al, 2009;Kawanishi et al, 2010;Markgraf et al, 1992;Noh et al, 2011;Pavlichenko et al, 2008;Sadamoto et al, 1998;Shinoda et al, 1996;Smith et al, 1997;Wang et al, 2010;Xu et al, 2009;Yonemori et al, 1996;Yun et al, 2007;Zhang et al, 2010). However, in rodent experimental stroke models, investigation of deficits in spatial memory using the Morris watermaze may be confounded by coexisting sensory and motor impairments.…”