Persistent impairment in cognitive functioning postoperatively is reported by clinical and animal studies, and is labeled as postoperative cognitive dysfunction (POCD). Evidence points to an exaggerated neuroinflammatory response resulting from peripheral systemic inflammation after surgery, with subsequent cytokine-induced glutamatergic excitotoxicity and synaptic impairment. These immunological changes, among many others, are also observed in Alzheimer’s disease. Memantine is an N-methyl-D-aspartate receptor (NMDAR) antagonist commonly used to treat Alzheimer’s disease. Surprisingly, little research exists on the role of memantine in preventing POCD. The purpose of this study is to investigate the effects of memantine on a spectrum of cognitive functions postoperatively. Mice were divided into 3 groups and each received treatment for 4 weeks. Placebo groups received a placebo then underwent either a sham procedure or a laparotomy procedure. The memantine group received memantine hydrochloride then underwent a laparotomy procedure. Cognitive tests were performed on postoperative days (POD) 1 and 7. Compared to sham-operated mice, placebo groups that underwent a laparotomy procedure showed impaired memory in the Morris water maze test, higher anxiety-like behavior in the open field and the elevated plus maze tests, increased depression-like behavior in the tail suspension test, and lack of preference for social novelty in the three-chamber test. On the other hand, memantine-treated mice that underwent a laparotomy procedure showed enhanced memory on POD7, improved depression-like behavior on POD1 and POD7, enhanced preference for social novelty on POD1, and no improvement in anxiety-like behavior. These findings suggest a potential protective effect of memantine in mice postoperatively on memory, depression-like behavior, and preference for social novelty.
The selective retrieval of some information may lead to the forgetting of related, but non-retrieved information. This memory phenomenon is termed retrieval-induced forgetting (RIF). Active inhibition is thought to function to resolve interference from competing information during retrieval, which results in forgetting. Epilepsy is associated with impaired inhibitory control that contributes to executive dysfunction. The purpose of this study is to investigate whether rats in a kindling model of epilepsy demonstrate normal levels of RIF. Rats were divided into two groups: saline and kindling. Pentylenetetrazole was injected intraperitoneally until the rats kindled. RIF was tested using a modified version of the spontaneous object recognition test, consisting of a sample phase, retrieval or interference phase, and a test phase. Exploration time for each object was analyzed. RIF was demonstrated in the saline group when rats subjected to the retrieval phase failed to discriminate between the familiar object and the novel object later in the test phase. Kindled rats, on the other hand, did not suffer forgetting even when they were subjected to the retrieval phase, as they spent significantly longer times exploring the novel rather than the familiar object in the test phase. Therefore, RIF was not observed in the kindling group. These findings indicate impaired retrieval-induced forgetting in kindled rats, which may be suggestive of a deficit in the inhibitory control of memory.
Key Clinical Message This case is the first published associated liver partition and portal vein ligation for staged hepatectomy procedure done successfully in Saudi Arabia, with excellent hypertrophic response to the liver remnant. This is a milestone in liver resection techniques in the country and the region.
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