Comparison between succinylcholine and rocuronium as neuromuscular blocking agents for electroconvulsive therapy in a patient with pseudocholinesterase deficiency.

We report here the anesthetic management of a patient with schizophrenia and pseudocholinesterase deficiency. Electroconvulsive therapy was performed using succinylcholine and rocuronium as the neuromuscular blocking agents in the first seven and latter six treatments, respectively. The recovery time from muscle relaxation after succinylcholine administration was remarkably longer than that after rocuronium-sugammadex administration. Rocuronium and sugammadex appear to be useful in situations in which succinylcholine is contraindicated.

[Masseter muscle rigidity after suxamethonium during induction and postoperative abortive malignant hyperthermia in a patient with esophageal achalasia].

A 38-year-old man diagnosed as esophageal achalasia developed masseter muscle rigidity after intravenous suxamethonium during anesthetic induction. Anesthesia was maintained with intravenous agents and epidural blockade, while the masseter muscle rigidity continued. After the surgery, his body temperature increased to 38.8 degrees C concomitantly with the appearance of myoglobinuria suggesting the occurrence of abortive malignant hyperthermia. These symptoms were dissolved by dantrolene administration. He was later proved to be negative with CICR test.

Antisense knockdown of spinal-mGluR1 reduces the sustained phase of formalin-induced nociceptive responses.

To examine the role of mGluR1 (a subunit of the group I metabotropic glutamate receptor) in the nociceptive responses of rats following a subcutaneous injection of formalin into the plantar surface of the hind paw, we delivered antisense oligonucleotides (ODNs) against mGluR1 into the rat lumbar spinal cord (L3-L5) intrathecally using an HVJ-liposome-mediated gene transfer method. Rats treated with a single injection of mGluR1 antisense ODNs into the intrathecal space of the lumbar spinal cord showed a marked reduction of the early-sustained phase of formalin-induced nociceptive responses, but not of their acute phase. The reduction of nociceptive behavioral responses became apparent at day 2 after the antisense treatment and lasted for 2 days. This corresponded to a long-lasting down-regulation (46%) of mGluR1 expression in the lumbar cord. This down-regulated mGluR1 was observed at day 2 and persisted until day 4 after the intrathecal infusion of mGluR1 antisense ODN. In contrast, rats treated with mGluR1 sense or mismatch ODNs showed none of these changes. These results suggest that mGluR1 may play a crucial role in the sustained nociception of formalin-induced behavioral responses.

Overexpression of Ca2+-permeable AMPA receptor promotes delayed cell death of hippocampal CA1 neurons following transient forebrain ischemia.

To examine the role of Ca(2+) entry through AMPA receptors in the pathogenesis of the ischemia-induced cell death of hippocampal neurons, we delivered cDNA of Q/R site-unedited form (GluR2Q) of AMPA receptor subunit GluR2 in the hippocampus by using an HVJ-liposome-mediated gene transfer technique. Two days prior to transient forebrain ischemia, we injected an HVJ-liposome containing cDNA of the GluR2Q-myc fusion gene into a rat unilateral hippocampus. In the absence of ischemic insult, overexpression of Ca(2+)-permeable GluR2Q did not cause any neurodegeneration in the cDNA-injected hippocampus. In ischemic rats, overexpression of Ca(2+)-permeable GluR2Q markedly promoted ischemic cell death of CA1 pyramidal neurons, while complete rescue of CA1 pyramidal neurons from ischemic damage occurred in the hippocampal hemisphere opposite the GluR2Q expression. Overexpression of the Q/R-site edited form (GluR2R) of subunit GluR2 did not affect the ischemia-induced damage of CA1 pyramidal neurons. From these results, we suggest that the Ca(2+)-permeability of AMPA receptors does not have a direct contribution to glutamate receptor-mediated neurotoxicity but has a promotive action in the evolution of ischemia-induced neurodegeneration of vulnerable neurons.

Antisense hippocampal knockdown of NMDA-NR1 by HVJ-liposome vector induces deficit of prepulse inhibition but not of spatial memory.

Considerable evidence suggests that an N-methyl-D-aspartate (NMDA) receptor plays a crucial role in memory and cognitive function. To identify the role of this receptor in higher functions of the brain, we delivered antisense oligonucleotides against an NMDA-NR1 subunit (NR1) to the hippocampus in rats using the HVJ-liposome-mediated gene-transfer method. NR1 hippocampal knockdown was performed by the focal injection of the NR1 antisense-HVJ-liposome complex into the bilateral hippocampus. The blocking effect of NR1-antisense on the expression of NR1 was confirmed by Western blot analysis. Spatial memory was tested by a water maze task, and sensorimotor gating was examined by prepulse inhibition (PPI). Western blot analysis demonstrated that the NR1-antisense treatment specifically provided the down-regulation (about 30%) of NR1 protein levels in the hippocampus. The water maze task showed that the antisense treatment did not affect spatial memory, while the PPI test revealed that NR1 hippocampal knockdown caused a deficit in sensorimotor gating. We conclude that mild dysfunction of hippocampal NMDA receptor causes sensorimotor gating deficit and relatively intact in spatial memory.

Antisense in vivo knockdown of synaptotagmin I and synapsin I by HVJ-liposome mediated gene transfer modulates ischemic injury of hippocampus in opposing ways.

Neurotransmitter release during and after ischemic event is thought to be involved in excitotoxicity as a pathogenesis for the ischemic brain damage, which is mediated by excessive activation of glutamate receptors and attendant calcium overload. To ascertain the role of transmitter release from nerve terminals in promoting the ischemic neurodegeneration, we delivered antisense oligodeoxynucleotides (ODNs) to synaptotagmin I or synapsin I into the rat brain by using HVJ-liposome gene transfer technique. The antisense ODNs were injected into the lateralventricle in rats 4 days prior to transient forebrain ischemia of 20 min. With a single antisense treatment, long-lasting downregulation of the transmitter release relating protein levels at overall synaptic terminals was achieved. The antisense in vivo knockdown of synaptotagmin I prevented almost completely the ischemic damage of hippocampal CA1 neurons, while the in vivo knockdown of synapsin I markedly promoted the ischemic damage of CA1 pyramidal neurons and extended the injury to relatively resistant CA2/CA3 region. The modulation of ischemic hippocampal damage by the in vivo knockdown of synaptotagmin I or synapsin I suggests that transmitter release from terminals plays an important role in the evolution of ischemic brain damage and therefore the transmitter release strategy by the use of antisense ODNs-HVJ-liposome complex is reliable for neuroprotective therapies.